TBA
"Bioactive glasses (BGs) are being increasingly investigated as antibacterial materials for developing scaffolds for bone tissue engineering (TE). Such applications are based on the biochemical reactions occurring on the BG surface in contact with the biological environment, which involve the (controlled) release of biologically active ions during BG scaffold degradation. Such ions are capable...
"Cancer is a complex disease system in which the extracellular microenvironment provides robust physicochemical cues to promote disease progression and resistance to therapy. Immunotherapies have been considered as an efficient therapeutic strategy to treat cancer and are being studied for their potential to improve prognosis and long-term survival of patients. While early clinical data shows...
"Polysaccharides belong to the most abundant biomaterials on earth. They form structural elements of plant and animal tissues, but many of them have also important regulatory functions towards cells, tissues and organs. Glycosaminoglycans (GAG) and other carboxylated and sulfated polysaccharides possess a bioactivity that is due to their high affinity to a plethora of proteins that belong to...
The plan for tissue engineering has always been to deliver human tissue products that can repair, regenerate, and replace our organs. As far as the heart is concerned, that plan has been punched - hard - by reality (Cit. Mike Tyson). Through the lens of my post-doctoral research at Harvard, we will review advancements in heart muscle engineering and examine some of the fundamental roadblocks...
"Quantum Sensing for measuring free radical generation in living cells
Romana Schirhagl
Groningen UniversityUniversity Medical Center Groningen, Antonius Deusinglaan 1, 9713AW Groningen, the Netherlands
Free radical generation plays a key role in many biological processes including cell communication, immune responses and maturation. However, radical formation is also a...
Introduction
Bone defects above a critical size exhaust the self-healing capacity of bone and in these circumstances intervention is needed to promote regeneration. In recent decades, an increasing number of tissue engineered bone grafts have been developed. However, expensive and laborious screenings in vivo are necessary to assess their safety and efficacy. Rodents are the first choice...
Elastomeric biodegradable scaffolds have been utilized as viable cardiovascular tissue surrogates in various applications, including cardiac patches, engineered vascular grafts, and heart valves. The interactions between cells and scaffold constitute an essential element in endogenous tissue growth and de novo tissue formation. Mechanical conditioning regimens are widely recognized as...
Bone is a frequent homing site for breast cancer metastasis. Unfortunately, the majority of patients diagnosed with primary breast cancer is often affected by bone metastasis from where cancer can reach other vital organs such as the lungs. Thus, it is vital that the process of metastatic attraction and homing is modeled in vitro, harnessing tissue engineering technology, generating viable...
Introduction
Bone tumour removal, traumas with large defects or infections, and degenerative diseases are the main catastrophic events impeding complete bone healing. Autologous and allogenic bone grafting, and biologically inert metallic devices have limitations such as non-availability of autogenous bone, risk of infectious disease transmission, subsequent surgical removal, and bacterial...
"Many biomaterials have been proposed to produce porous scaffolds, nanofibers and nanoparticles for different medical treatments and applications. Systems combining natural polymers and synthetic biodegradable polymers offer particular properties adequate for those demanding applications. Those biomaterial systems can be tailored with enhanced mechanical properties, processability,...
Introduction:
Implant infection, due to bacterial contamination, is a significant problem that represents one of the main causes of implant loss over time. In addition, the incidence of antibiotic resistance is steadily increasing, and alternative ways to fight or prevent infection have become the subject of biomedical research, and several surface modification and coating techniques have...
Background and Aims: Cholangiocarcinoma (CCA) is an aggressive, heterogeneous cancer with low survival rates. Patient-derived cholangiocarcinoma organoids (CCAOs) hold potential for understanding disease progression and developing novel treatment options, based on their ability to mimic the original tumor. However, a hallmark of cancer is the disturbance of morphological cues resulting in...
Introduction
Extracellular matrix communicates to the nuclear environment by external stimuli that affect Lamina organization and chromatin distribution [1]. It is known that integrins transmit mechanical stimuli to the actin filaments in turn connected to the LINC complex consisting of Nesprin and SUN proteins [2]. SUN proteins are supposed to link the nuclear Lamina [2], that rearranges...
Introduction: Pancreatic cancer is a devastating malignancy, and treatment options are very limited [1]. Progression of the disease and resistance to therapy are mediated by the tumour microenvironment (TME), which is composed of excessive amounts of extracellular matrix proteins, as well as stromal and immune cells, acting as a physical barrier for drug delivery [1-3]. Cell-secreted factors,...
Introduction
Since the discovery of bioactive glasses (BG) in the late 60s [1], the research in this area has significantly increased to obtain compositions with multiple functionalities not only from the materials aspect but also to provide a favorable biological response for tissue regeneration. BGs have the ability to react with the surrounding environment and bond to hard tissue. This...
Introduction
Realization of tissue engineered cardiac constructs has progressed with the combination of induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and additive manufactured frameworks for guided repair[1]. Recently, we developed hexagonal 3D microfiber scaffolds with melt electrowriting (MEW). These scaffolds support contracting hiPSC-CMs and promote tissue organization...
Introduction: Liver fibrosis is caused by progressive accumulation of extracellular matrix (ECM) coupled with chronic inflammation. Advanced liver fibrosis results in increased risk of liver cancer, cirrhosis, portal hypertension and liver failure, resulting in the need for liver transplantation. Studies of the mechanisms that promote fibrosis are necessary to understand this multi-faceted...
"Osteoarthritis, a degenerative disease of the cartilage and subchondral bone, is becoming more prevalent due to an aging world population. Although some clinical interventions are available, the solutions are often temporary due to fibrocartilage formation in the long term, which has mismatching mechanical properties. Tissue engineers have been designing osteochondral (OC) scaffolds to induce...
Introduction: Stem cells are being tested in clinical trials for cardiac repair. Bone marrow derived allogeneic (unrelated donor) mesenchymal stem cells and induced pluripotent stem cells (iPSC) have emerged as ideal cell types for cardiac repair and regeneration. Outcome of initial allogeneic stem cells based clinical trials was positive. There were no significant side effects observed after...
Nanomedicine, where therapeutic or diagnostic agents are coupled with nanoparticles (NP), offers opportunities for more efficacious treatments and accurate diagnosis of severe clinical conditions. Polymeric, lipidic, metallic or ceramic NP have been considered as carriers of these agents, but their translation into clinics requires a thorough assessment of their biocompatibility and...
Introduction: In the last years, partly given to the changes in the age structure of the population, there has been a skyrocketing increase of the number of orthopaedic surgeries [1]. With the rising number of implantations, the absolute number of complications is inevitably increasing at the same pace, causing not only distress for the patients but also a significant economic burden [2]. One...
Introduction:
Regenerative medicine is focusing the attention on immune engineering strategies taking advantage of biomaterials to influence stem cells fate and to stimulate the production of immune modulatory factors to be employed in cells free treatment (1). The Graphene Oxide (GO) was proved to be able to affect stem cells behaviour and to modulate their immune response (2). According to...
"[Introduction] In recent years, biomolecules have been used to functionalize the surface of scaffold materials to support tissue engineering applications. For the functionalized surface for enhancing the cell culture efficiency, peptide coating has been one of the major strategies to provide surface property mimicking the extracellular matrix (ECM). In the past days, the cell adhesion...
Modeling the cardiac pathological traits would be of paramount utility to elucidate possible targets of new therapeutics for unmet pathology (e.g., Dilated Cardiomyopathy (DCM [1])). Traditional in vitro systems lack the complexity of human physiological conditions, resulting poorly reliable for tissue engineering studies. Organs-on-chip (OoC) have been shown to be a promising alternative,...
INTRODUCTION:Termed as the ‘silent killer’,epithelial ovarian cancer (EOC) earns its nickname due to its high mortality rate, with 5-year survival rates of 46%,46.5% and 38% in UK, USA & Europe respectively.This has been attributed to some extent to the EOC’s high recurrence rate and resistance to currently available platinum based chemotherapeutic treatment methods. Hence,society,...
INTRODUCTION: Pelvic Organ Prolapse (POP) is characterized by the descendance of the pelvic organs due to weakening of the pelvic floor. Up to 20% of the women get recurrence after surgery, implying that surgical outcomes are poor due to suboptimal wound healing[1]. Tissue engineering has shown great potential in stimulating regeneration by combining cells, biomaterials and biochemical cues....
"Introduction
Implantation of biomedical devices is followed by immune response to the implant, as well as occasionally bacterial and yeast/fungi infections (1-3). In this context, new implant materials and coatings that deal with medical device-associated complications are required. Antibacterial and anti-inflammatory materials are also required for wound healing applications, especially in...
Cell-extracellular communication in granular systems might be explored for tissue engineering and to understand and mimic physiological responses. Particulate systems can be designed as attractive platforms with free movement controlled mainly by intracellular forces and cell migration. We here explore the possibility that the size of the particles composing these systems might have a role in...
Restoration of cardiac functionality after myocardial infarction represents a major clinical challenge1. Recently, we found that transient transfection with a microRNA combination (miRcombo: miR-1, miR-133, miR-208 and 499) is able to trigger direct reprogramming of adult human cardiac fibroblasts (AHCFs) into induced cardiomyocyte (iCMs) in vitro2. However, achieving efficient direct...
Parkinson's disease (PD) is a neurodegenerative disease clinically characterized by motor disabilities. Current therapies are not being fully effective. Remarkably, the neuroregulatory molecules secreted by mesenchymal stem cells (MSCs) have been suggested as an alternative therapy. However, direct injection into the brain is the delivery approach that has been used in pre-clinical models....
INTRODUCTION: Bacterial antibiotic resistance increases every year, creating an urgent need to develop new antibacterial materials. Gallium has been studied since the 1970s as an effective treatment for bone diseases and has recently shown antibacterial activity against different bacterial strains. Therefore, gallium doped hydroxyapatite (GaHAp) could be used as an antibacterial agent. The aim...
Smart materials, that react in a controllable and reversible way to external stimuli by varying a specific physical or chemical quantity, show great potential for the development of advanced biomedical strategies, including biosensing, tissue regeneration and repair, immuno- and cancer therapy.1 Among the different types of smart materials, piezoelectric ones, that convert mechanical...
Introduction: The assessment of bioaccessibility and bioavailability of orally-ingested compounds is key to determine their efficacy and safety. However, there is a lack of toxicological studies that combine simulated gastrointestinal (GI) digestion with subsequent intestinal absorption. Many studies expose cells directly to pristine bioactive substances, failing to consider the series of...
Introduction
Bone infections (osteomyelitis) are difficult to treat due to the formation of biofilms, antibiotic resistance, and limited penetration of systemic antibiotics to infection site(1). Highly-porous collagen-hydroxyapatite (C-HA) scaffolds have proven capacity to regenerate critical-sized bone defects in vivo and human clinical trials(2). However, they still lack appropriate...
Introduction: Bioengineered 3D cancer models allow the deconstruction of the tumour microenvironment in vitro to recreate the dynamic interactions between its extracellular and intracellular components. These bioengineered systems strongly rely on Matrigel, an undefined animal-derived matrix, to support the growth of cancer spheroids and organoids [1]. Despite its wide usage, Matrigel has poor...
Introduction: Among scaffold preparation approaches, biofabrication can provide tridimensional scaffolds with precise and defined architectures that can promote tissue integration and neoangiogenesis after implantation (1). Therefore, the evaluation of tissue ingrowth and vascularization of 3D printed scaffolds is a crucial step in establishing a functional scaffold that could direct the...
Introduction
Current tissue engineering treatment strategies for end-stage articular cartilage fail to produce long term functional cartilage tissue. Here, melt electrowriting (MEW) is used to fabricate 3D scaffolds with micro-resolution to mimic the structural properties of the native cartilage extracellular matrix[1]. These scaffolds are activated using atmospheric-pressure plasma jet...
INTRODUCTION: Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, contributing a huge burden on healthcare providers. Myocardial infarction (MI) is one of the most fatal results of CVDs as it can lead to ultimate heart failure. Available treatments are used to mitigate many of the symptoms of MI, however they are not designed to repair the damaged tissue. A proposed...
"Bioinspired polymer processing, with focus on improved control over biomaterial structure-function, is a research strategy that can play a critical role in facilitating the translation of a biomedical device. In this work, we utilize the specific example of tissue engineered heart valves to demonstrate this notion.
Valvular heart disease is currently treated with mechanical valves, which...
"Organs are complex systems, comprised of different tissues, proteins, and cells, which communicate to orchestrate a myriad of functions in our bodies. Technologies are needed to replicate these structures towards the development of new therapies for tissue and organ repair, as well as for in vitro 3D models to better understand the morphogenetic biological processes that drive organogenesis....
Cellular senescence is characterized by an irreversible cell cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP), which is a major contributor to aging and age-related diseases. Clearance of senescent cells has been shown to improve brain function in mouse models of neurodegenerative diseases as well as obesity. However, it is still unknown whether senescent...
The creation of bioinks that can both support cells during the fabrication process and lead to advanced tissue function post-processing remains a challenge. If the tissue engineering community wishes to unlock the potential of 3D biofabrication techniques, new materials must be designed to meet these needs. In our lab, we take a look at new strategies with dynamic hydrogels as a potential...
Articular cartilage and osteochondral defect repair remain major clinical challenges. Biomaterial scaffolds currently in clinical use in orthopaedic medicine do not accurately mimic native tissues, and therefore do not preferentially promote tissue-specific regeneration when they are colonised by endogenous stem/progenitor cells post implantation. Tissue-specific extracellular matrix (ECM)...
Supplement-free induction of macrophage polarization solely through the topography of materials is an auspicious strategy but has so far significantly lacked behind the efficiency and intensity of media-supplementation based proto-cols. We investigated Melt-Electrowriting (MEW) for the fabrication of fibrous 3D scaffolds made from poly(ε-caprolactone) (PCL) and advanced the precisely defined...
"Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fibrotic tumors, which can possess up to 90% tumor stroma of the total tumor mass (1). The tumor stroma is comprised of cancer-associated fibroblasts (CAFs), extracellular matrix (ECM) and many immune cells. The physical and biochemical characteristics of the tumor stroma control cancer cell proliferation, invasion, and...
Chronic kidney diseases (CKD) affect approximately 10% of worldwide population [1]. Currently in vitro models fail to mimic the complexity of the kidney essential for relevant in vitro studies. CKD can be caused by a multitude of factors spanning from nephrotoxic events, especially when exposed to cytotoxic compounds (e.g., antibacterials, corticosteroids, anti-cancer drugs) up to viral...
Extrusion bio-printing is the most direct and inexpensive method for printing three-dimensional cell models. This technique provides interesting solutions to generate more complex architectures than the already existing 3D models but still presents significant drawbacks that once solved will improve its field of application in regenerative medicine and advanced 3D biological models. To print...
INTRODUCTION: Mesoporous bioactive glass nanoparticles (MBG NPs) have received a significant amount of interest for their potential to treat cancer cells with high drug loading capacity and excellent stability, providing a controlled drug release platform into the malignant tumor [1]. Although enhanced permeability and retention (EPR) effects allow MBG NPs to accumulate at tumor sites, the...
"Introduction: Decellularization creates cell-free collagen-based extracellular matrices from native organs, which can be used as scaffolds for regenerative medicine applications1-8. This technique has gained much attention in recent times. However, there is still a limited understanding of scaffold responses in vivo post-transplantation and ways we can improve scaffold durability to withstand...
T.B.C.
41935604206
Introduction
There is a large number of synthetic polymers, which are generally suitable as implant materials due to their chemical, biological or mechanical properties. What many of them have in common, however, is the challenge of growing properly into the body, which poses design demands specifically to the implant’s surface. Requirements that many conventional plastic processing methods...
"Almost 160 clinical trials of tissue engineered products (TEPs) currently registered in ClinicalTrials.gov databases as well as the continuously growing record for TEPs under clinical investigations starting from the year 2006, can be taken as one of the many measures of success of tissue engineering as an applied science discipline. On the other hand, the number of TEPs on the medical market...
The reconstruction and replacement of musculoskeletal tissues have been extensively investigated in the last decades. Trauma injuries and degenerative diseases are the most common causes reported worldwide. Stem cells play an important role in tissue regeneration and have been successfully applied in musculoskeletal research, especially due to the low self-repair capability of tendons,...
"Introduction:
Articular cartilage facilitates the frictionless movement of synovial joints, however, due to its avascular and aneural nature, it has limited ability to self-repair. Current treatments for cartilage defects elicit variable results – an issue that the field of tissue engineering has aimed to address; however, the inability to mirror the complexity of native tissue with...
Introduction
Melt Electrowriting (MEW) is an versatile electric-field assisted fiber forming technique that has convincingly shown its potential for tissue engineering scaffolds both in vitro and in vivo. The additive manufacturing principle of MEW offers unparalleled possibilities to create precisley defined fibrous 3D architectures. The potential of design freedom with MEW is still largely...
Introduction: Developing more predictive in vitro platforms for biomedical research remains a major challenge in tissue engineering. 3D bioprinting allows patterning of cell-laden biomaterials into hierarchical structures. Volumetric bioprinting (VBP) is a novel light-based approach that tackles challenges posed by conventional approaches, through the layer-less biofabrication of viable and...
Understanding the key players in cancer progression is essential for the development of effective therapies. Aiming to pinpoint the roles of biochemical and biophysical factors involved in malignancy, tissue engineers developed in vitro cancer models of increasing complexity [1]. Three-dimensional (3D) bioprinting techniques were extensively used in this endeavor [2,3] due to their ability to...
Biobanking refers to the process by which samples of human body fluids, tissues or cells are collected to provide samples for different research purposes. Initially, the term biobank appeared in the scientific literature to describe human population-based biobanks.
Biobank is nowadays recognised as an organized collection of samples and associated data describing donor, stored for future...
Introduction: Current primary liver cancer models fail to truly encompass the human tumour immune microenvironment, exacerbating a recognised discord between the preclinical and clinical successes of emerging (immuno)therapeutics. The organotypic 3D culture of human precision-cut tumour slice (PCTS) is a cancer explant model which retains tumour specific histoarchitecture, aetiological...
Senescent cells, induced by various stressors, present a heterogenous population of irreversibly cell cycle arrested cells. They release pro-inflammatory compounds into surrounding tissue, collectively known as senescence associated secretory phenotype (SASP). Higher frequency of senescent cells is present during the developmental phase, regeneration and in aged organisms. Their accumulation...
"Introduction
Prolonged alveolar air leaks are post-surgical complications to routine lung resections and biopsies that are a significant cause of patient morbidity. Extended duration of chest tube drainage and emergency revision surgeries are the standard approaches for its clinical management. Transplantable decellularised pleural membrane patches as adjuncts to traditional intraoperative...
Introduction:
Recently, conductive hydrogels have garnered significant attention and permitted momentous improvements in neuroscience due to their tissue-like softness, chemical steadiness, and sufficient electrical conductivity.(1) They have been utilized as interfaces for neural electrode arrays to improve their biocompatibility and lower protein adsorption. In particular, these materials...
Cardiovascular diseases are the major cause of death worldwide. The lack of autologous vessels that can be used in cardiovascular surgeries compel engineers to look for nowel solutions. The main assumption of vascular tissue engineering is to design and produce functional materials that replace damaged blood vessels and restore their proper functions. Tissue-engineered vascular grafts with...
"Introduction
Biodegradable polymeric scaffolds face a growing use in tissue engineering. However, changes in material properties during degradation can impact drastically the scaffold durability and therefore the efficiency of tissue reconstruction. Few studies focus on approaches allowing the prediction of the scaffold lifetime, while there is a need for strategies using accelerated testing...
Chronic kidney disease (CKD) is characterised by the gradual loss of renal function. It affects approximately 10% of the population worldwide, and the only treatment is aimed to slow down the progression of kidney damage. Ultimately, CKD results in end-stage renal disease (ESRD), which can only be treated with dialysis or renal transplant. However, both options are far from ideal and cannot be...
Introduction: The surge in clinical need for bone tissue restoration together with limitations of existing treatments calls for the development of alternative strategies. Tissue engineering has been proposed towards the formation of bone graft substitutes capable of driving repair. Previously, we demonstrated the possibility of generating engineered cartilage grafts using a human mesenchymal...
Mesenchymal stem/stomal cells (MSCs) are often studied for their possible tissue engineering applications. During in vitro expansion, however, MSCs enter a state of permanent growth arrest while remaining metabolically active; this phenomena is known as cellular senescence. Senescence can negatively affect tissue homeostasis and an increased number of senescence cells can be found in...
"INTRODUCTION
Cancer early detection is pivotal to patient survival. The small non-coding nucleic acid sequences, microRNA (miRNA) are a captivating molecular target for cancer early detection. miRNA are dysregulated during the early stages of cancer1, it is found in stable amounts in blood plasma and serum. Therefore, a minimally invasive liquid biopsy screening device would allow for point...
Introduction
3D bioprinting has emerged as a promising technology for fabricating artificial tumors as it allows the fabrication of complex models recreating tumor physiology. The importance of the extracellular matrix (ECM) in tumor progression, cancer cells and stromal cells crosstalk and drug resistances, has motivated the development of more biomimetic tumor-ECM bioinks that recapitulate...
Collagen fiber network architecture in the native heart valve leaflets is characterized by preferential orientation and curvilinear arrangement that allow adequate stress distribution and effective leaflet coaptation. Specifically for the mitral valve, collagen fibers are preferentially aligned towards the circumferential direction with a curvilinear arrangement that runs from the...
"Introduction:
Highly porous biodegradable scaffolds made of polycaprolactone (PCL) and ceramic designed as three-dimensional (3D) guiding structures with rectilinear filling to facilitate bone regeneration have successfully been translated from preclinical studies into clinics as part of a scaffold-guided bone tissue engineering (SGBTE) concept. However, advances in 3D printer technology now...
Native tissues are characterized by its 3D organization and distribution of cells, with specific cell-cell and cell-extracellular matrix (ECM) interactions dictating tissue function. The spatial distribution of cells and ECM in tissues is not arbitrary. There are specifically located cell populations for generating interconnected lumen structures, creating a fundamental structure-function...
"INTRODUCTION: Burn injuries propound copious challenges to clinical care and leaves the patient traumatized for years with scars. Even so, scarring walls off foreign bodies and seals injured tissue, it curb the movement and cede the cosmetic appearance of the skin. This wound healing defect is coupled with impaired cytokine expression. Upon tissue damage, the injured skin residents release...
"Introduction
Growing clinical demands for electrical stimulation-based therapies for central nervous system applications requires the development of conductive biomaterials balancing conductivity, biocompatibility, and mechanical performance. Traditional conductive materials often induce scarring, due to their stiffness and poor biocompatibility, hindering their clinical translation and...
INTRODUCTION
Cardiovascular disease is one of the major causes of death worldwide [1]. Synthetic vascular grafts (SVG) and autograft vessels are the current treatment modalities but, are ineffective for vessels with a diameter lower than 6 mm due to compliance mismatch [2] and limited in both supply and anatomical variability, respectively. An alternative solution is via tissue engineered...
Inflammation is a protective response to damaged tissue and foreign bodies, such as biomaterials, and is usually considered to be negative. More recently, however, the active anti-inflammatory, pro-regenerative role of various mediators and inflammatory cytokines from immune cells have become widely recognised. In particular, macrophages play an essential mediating role in modulating...
Treatment options for triple-negative breast cancer (TNBC) are limited. Current 2D cancer models fail to accurately model the tumour microenvironment of breast cancer. Alterations to extracellular matrix (ECM) composition have been shown to play a key role in the epithelial-mesenchymal transition (EMT) process involved in breast cancer progression (1). This highlights the need for the...
"Introduction: Musculoskeletal ailments caused by cartilage damage are common, and thanks to more modern diagnostic methods, they are more often recognized. Moreover, cartilage diseases progress with age and result from injuries, becoming a dominant problem in orthopedic surgery. The conducted research aims to produce conjugates for cartilage regeneration based on chondrogenic differentiation...
"INTRODUCTION
Osteoarthritis (OA) is the most prevalent degenerative joint disorder, but no reversing therapies are currently available [1]. This is mainly due to the disease complexity, that involves a failure of the entire joint, and to the disease multifactorial etiology [2]. Taking all this into account, a gap of knowledge still exists on initial disease mechanisms, linked to the...
"Introduction: Ischemic heart disease is a major cause of human death worldwide owing to the heart’s minimal ability to repair following injury. Despite medical advances, current treatments are not able to regenerate the damaged heart tissue. Therefore, alternative strategies are being assayed to identify the proper strategy to induce heart regeneration. In this sense, cardiac tissue...
The main risk factors for aseptic loosening and implant failure are wear and corrosion of metal implants. Despite a passive oxygen layer forming on many implant materials, electrochemical reactions can occur [1]. Oxidation and reduction reactions take place, resulting in a constant exchange of electrons and ions between the metal and the surrounding fluid [2]. The release of metal ions in...
Introduction
Lung cancer is the leading cause of cancer mortality with poor prognosis due to late stage diagnosis, drug resistance and high risk of relapse. There is a high need for tissue engineered 3D models that can recapitulate tumor heterogeneity and complexity to understand the cellular mechanisms leading to lung tumorigenesis, metastasis and drug responses. Future of precision oncology...
INTRODUCTION: Major challenges in bioprinting tissues with functional, native-like behavior revolve around enabling the use of hydrogels with low elastic modulus, while also ensuring high shape fidelity and printing resolution. Such materials are necessary to allow cells to migrate, and to facilitate intercellular communication and reorganization of the neo-synthesized extracellular matrix. In...
By its avascular nature and limited healing potential, articular cartilage (AC) defects are still challenging to cure, resulting in degenerative diseases such as osteoarthritis. Several clinical techniques aim to repair the AC; however, load-bearing and fully functional tissue recapitulation remain a significant hurdle. In the last few decades, tissue engineering has given hope for resolving...
Introduction
Currently used prosthetic heart valves show multiple limitations, including a reduced ability to regenerate. In this study we developed a three-layered electrospun heart valve using a dual electrospinning setup with a special 3D printed collector. In this manner, not only the microscopic but also the macroscopic structure of native heart valves was imitated. Biocompatibility of...
"Introduction. Large critical size bone defect is one of the most challenging pathologies in orthopaedic surgery. NVD‑003 is an autologous scaffold-free cell-based osteogenic implant intended to improve bone healing in severe pathophysiological conditions. This study aims to investigate the therapeutic potential of NVD-003, an osteogenic graft derived from human adipose stem cells.
Methods....
"Introduction: IL-1β and IL-17 are highly present in the synovial fluid after joint trauma and are plausible factors in the development of post-traumatic osteoarthritis (PTOA). Although a growing number of studies have identified a role for IL-17 in OA, the mechanisms underlining the pathophysiological role of IL-17A in early PTOA disease in healthy joint cells remains unclear. We performed a...
"Introduction: Vascularization is a critical aspect of every tissue engineering (TE) approach, especially in 3D constructs. The formation of a network of capillaries is necessary to ensure adequate delivery of nutrients and oxygen to cells within the constructs, as well as fast anastomosis with the host’s vasculature after implantation. Pre-vascularization of these constructs before...
Although the secretome of mesenchymal stem cells (MSCs) has a great potential to be used in CNS regenerative therapies, tissue derived MSCs are a limited source which often need to be surgically harvested and present intrinsic donor variability. Induced pluripotent stem cells (iPSCs) conversely, can be easily generated and highly expanded from accessible somatic cell sources and differentiated...
Introduction
The kidney plays a crucial role in drug development, as it dictates drug clearance and is a target for drug-induced toxicity. Nephrotoxicity of candidate drugs is one of the major reasons for drug attrition during preclinical, clinical and post-approval stages of drug development. These failures during the final stages of the drug development process are partially caused by the...
INTRODUCTION: Most epithelial cancer cell populations undergo an epithelial to mesenchymal transition (EMT), acquiring a more aggressive phenotype1. Mesenchymal cells are more motile and have the ability to remodel the extracellular matrix. This mechanical interaction with the surrounding matrix can be measured by bulk and single cell force generation. In this study we aim to use 3D in vitro...
"Introduction
Type 1 diabetes (T1D) is a disease, which affects milions of patients. Islet or pancreatic transplantation is a method of treating complicated T1D. The limitation of these methods is the lack of organs for transplantation. 3D-bioprinting using living cells could be a solution. We present results of bioprinted bionic pancreas on mouse and pig model.
Materials and...
"Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. This talk will describe how spheroid bioprinting in suspension baths can be used to engineer...
Brain organoids represent the 3D tissues that recapitulate the structure and function of the developing human brain. Much efforts have been made to advance the regionalization and to utilize the brain organoids to study human diseases. We developed region-specific cortical organoids and used them to study Rett syndrome. Since neuroectoderm differentiation of the human embryonic stem cells...
TBA
"Image-based analysis of cells is a powerful modality to measure and record the high content information which reflects the cellular status during their culture. Although morphology has been known for a long to contain significant information to monitor the transitions of cellular status, their analysis has been limited to experience-based interpretations. However, by the recent rapid...
Whey protein isolate (WPI) is an inexpensive byproduct from the dairy industry which can be processed into autoclavable hydrogels with high compressive strength which support the adhesion, growth and differentiation of cells which can be applied in bone regeneration. Furthermore, WPI hydrogels can solubulized hydrophobic molecules and hence serve as a delivery vehicule for hydrophobic...
*Introduction: Despite the crucial role of the muscle extracellular matrix in the organotypic organization and the transmission of mechanical force, most 3D muscle models do not mimic its specific characteristics, namely its biochemical composition, stiffness, anisotropy and porosity. In vivo, muscle extracellular matrix possesses specific characteristics such as a high amount of aligned...
We will discuss the influence of cell shape and mechanical load on cell adhesions, cytoskeletal structure, cell signaling and transcription as determinants of cell fate and function.
83871204866
INTRODUCTION
Creating biofunctional scaffolds could potentially meet the demand for patients suffering from bone defects without having to rely on donors or autologous transplantation. 3D printing has emerged as a promising tool to fabricate scaffolds with high precision and accuracy by computer design using patient-specific anatomical data1. Among other relevant key points for 3D-printed...
The human brain is unique in size and complexity, but also the source of some of the most devastating human diseases. While many of these disorders have been successfully studied in model organisms, recent experiments have emphasized unique features that can not easily be modeled in animals. We use cerebral organoids to recapitulate those features in vitro and to test their role in human...
INTRODUCTION
Myocardial infarction (MI) leads to a significant loss of cardiomyocytes followed by the progressive formation of a non-contractile fibrotic scar. Recently, the use of microRNA (miRNA) has emerged as a promising strategy for cardiac regeneration. Paoletti et al. demonstrated that the transient transfection with four microRNA mimics (termed “miRcombo”) can induce the direct...
"Tracheal damage is associated with the narrowing, weakening and discontinuity of the conductive part of the lower respiratory tract. Extensive defects cannot undergo end-to-end anastomosis and current approaches present poor outcomes due to weak mechanical properties, poor re-epithelialisation and vascularisation of the implanted graft. Herein, we investigated the use of collagen-based...
"INTRODUCTION: Myocardial infarction (MI) is an ischemic and inflammatory event majorly orchestrated by macrophages from infiltrating monocytes. These macrophages play a critical role in deciding the fate of the heart post-MI. However, there is no cardiac disease model in existence that incorporates an immune response. Hence, the aim of this project is to develop a humanized model of MI, using...
Spheroids are one of the well-characterized 3D cell culture approaches for drug screening and therapeutic studies. Magnetic levitation (MagLev) is a newly developing approach to form 3D cellular structures and spheroids [1,2,3]. Magnetic levitational assembly of cells provides rapid, simple, cost-effective 3D cell culture formation while ensuring scaffold-free microenvironment. Here, our...
Extensive defects of the upper extremity cause significant patient burden, including disability and social stigma. Approximately, 500,000 bone defects are reconstructed annually in the USA alone at a cost of ~$2.5 billion, due to factors including donor site harvest and lengthy operative times. Bone defects >5cm are usually reconstructed with autologous vascularized bone transfer (bone from...
INTRODUCTION: Embedded 3D bioprinting is a promising approach to engineer complex tissues such as patterned or pre-vascularized tissue constructs1,2. However, the resulting tissue constructs are often mechanically weak, unable to form mechanical or chemical gradients, and lack on-demand tunability. Here, we report on dual crosslinkable dextran-based hydrogel as a hydrogel bath for embedded...
"Introduction
In present times, implant development focusses on optimizing biocompatibility, mechanical strength, and reproducibility. Although cardiovascular implants currently available on the market are medically established and therefore widely used, they have a limited lifetime which also impacts the mechanical properties and functionality. Additional issues are the formation of blood...
"RECONSTRUCTION OF FUNCTIONAL GRADIENTS USING MELT ELECTROWRITING
Frendion F.S.J. Marchena1,2, Magdalena Gladysz1,3, Malgorzata K. Wlodarczyk-Biegun1,4
1Polymer Science - Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
2Hanze University of Applied Science in Groningen, Zernikeplein 7, 9747 AS Groningen, The...
"Introduction
In silico methods integrate physical and biochemical models with computational tools, and are a powerful support for tissue engineering. They are particularly relevant for studying organoids and assembloids: the multiplicity of parameters which condition organoid growth and morphology can be explored in virtual models, facilitating experimental design, and enabling prediction...
AN INDUCED PLURIPOTENT STEM CELL-BASED MODEL TO STUDY THE MECHANOBIOLOGY OF MYOCARDIAL FIBROSIS
Francesco Niro1,2, Daniel Pereira De Sousa1,2, Jorge Oliver-De La Cruz1, Soraia Fernandes1, Stefania Pagliari1, Marco Cassani1, Vladimir Vinarsky1,2 Ece Ergir1, Giancarlo Forte1,2
- International Clinical Research Center (ICRC), St Anne’s University Hospital Brno
- Department of Biomedical...
An open source extrusion bioprinter based on the E3D motion system and tool changer to enable FRESH and multimaterial bioprinting
Adam Engberg1, Christina Stelzl1, Olle Eriksson1, Paul O’Callaghan1 & Johan Kreuger1
1 Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Bioprinting is increasingly used to construct complex 3D cell models and tissue constructs for...
Introduction: Chondrocytes beneath the joint surface display a distinct superficial chondrocyte spatial organization (SCSO), which is a marker of tissue ultrastructure and function that undergoes a proliferative remodeling in early osteoarthritis [1,2]. Cellular filamentous actin (F-actin) and cell volume, two proliferation cofactors, change with osteoarthritis and might contribute to...
"Introduction
Cell infiltration is essential for the repopulation of dense materials in tissue engineering. During that process, several factors, such as scaffold topography, mechanical properties or porosity play a key role. These acquire special importance when designing the materials to substitute and regenerate articular cartilage. Because of their similar structure and composition,...
"Introduction. Irrespective of the several scaffold designs that have been investigated in the last 30 years, the actual number of scaffold guided bone tissue engineering (SGBTE) approaches that were able to reach clinical application are few. Most of these approaches fail translation into clinical settings firstly because outcomes of scaffold design properties and host immune responses...
"Introduction
Osteosarcoma (OS) is the most frequent malignant bone tumour with a survival rate of less than 25% in metastatic disease. Treatment is a combination of surgical resection and systemic chemotherapy with doxorubicin (DOX). However, this can cause serious long-term adverse effects. To overcome this limitation, we have developed an advanced rat OS model that converges tissue...
Introduction
With continued progress of wearable sensor technology and drug-screening in-vitro models, there is a need for more advanced biomaterials and scaffolds to enhance electrical performance for stimulation and recording.1 Poly(3,4-ethylenedioxythiophene):poly-styrenesulfonate (PEDOT:PSS) is an electroconductive polymer often applied within biosensors and more recently as scaffold in...
"Introduction: Chronic ulcerative oral mucosal inflammatory diseases, including oral lichen planus and recurrent aphthous stomatitis, are painful and highly prevalent, yet lack effective clinical management. These conditions are usually treated with either topically applied or systemically-delivered corticosteroids depending on severity with varying degrees of success. In recent years systemic...
3D printing has revolutionized the manufacturing of volumetric components and structures in many areas. Several fully volumetric light-based techniques have been recently developed thanks to the advent of photocurable resins, promising to reach unprecedented short print time (down to a few tens of seconds) while keeping a good resolution (around 100 microns). However, these new approaches only...
The expansion culture of cells is an essential process for manufacturing cells for therapeutic use. However, it is also an activity with a huge dilemma. This is because for clinical cell therapy treatment, and also for preparing cells for establishing cell bank, it is strongly required to expand cell number by passage culture to prepare a sufficient number of cells for applications, however at...
"Introduction: Mitochondrial dynamics and metabolic alterations play a pivotal role in neuron maintenance and differentiation during early human neurodevelopment. Brain organoids (BO) derived from human induced pluripotent stem cells (hiPSC) provide a unique model to study developmental stage-specific sensitivity of mitochondrial dynamics to different microenvironmental cues. Our previous...
INTRODUCTION
With a growing demand for effective regenerative medicine therapies, more sophisticated tissue-engineered in vitro models are required for a better understanding of the fundamental biological processes that underlie regeneration. To tackle this need and further comprehend these processes, new technologies are emerging in the tissue-engineering field. The state-of-the-art...
"Introduction -
The development of novel biocomposite formulations has significantly contributed to the biomedical field- specifically within translational and clinical applications. This study centres on the polyhydroxyalkanoates-based copolyester superfamily of materials, with a particular emphasis on the poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] copolymer as a novel...
"INTRODUCTION
One of the main functions of guided bone regeneration (GBR) barriers are to preserve the bone graft and maintain its mechanical stability during the healing process. Personalized metallic meshes meet GBR demands as well as a good predictable tissue regeneration1. Although they offer good performance in terms of tissue regeneration, these metallic meshes present several...
"Breast cancer (BCa) is the most common cancer amongst women worldwide and the leading cause of cancer related death. The triple negative BCa (TNBCa) subtype is associated with a particularly aggressive clinical behavior including an early peak of fatal distant metastasis, predominantly to bone. Routine systemic chemotherapeutic treatment with doxorubicin (DOX) is limited due to its severe...
In this seminar, I will provide a basic overview of the developmental mechanisms underlying the emergence of functional areas in the cerebral cortex. I will start by providing an overview of studies performed in rodents. Subsequently, I will transition to describe our studies in human, highlighting similarities and differences in progenitor cell diversity between mice and humans, I will...
Purpose: Each year, 15 million people suffer from a myocardial infarction and heart failure, resulting in one of the leading causes of death worldwide. Owing to the fact that the adult mammalian heart lacks a regenerative capacity, the ischemic cardiac muscle is replaced by scar tissue. While the mechanisms involved in fibrotic tissue formation are still elusive, the immune system is known to...
"INTRODUCTION:
Extracellular matrix (ECM) protein is often used in cell culture to provide developmental cues for cells such as skin cells. This is especially important for the generation of epidermal models as without a dermal compartment the keratinocytes are reliant on the ECM coating to provide them with a foundation to adhere to and for pro-developmental cues. A major limitation of most...
Introduction:
Tendon tissues have highly-anisotropic physical properties that are responsible for its biomechanical performance and biological organization. The recreation of its 3D extracellular matrix (ECM) and cellular patterns in bioengineered constructs remains challenging. The concept of magnetically-assisted 3D bioprinting with magnetic hydrogel bioinks can be exploited to fabricate...
Using a machine learning-supported approach for assessing and predicting the susceptibility of articular cartilage to mechanical trauma-induced changes in cellularity
M. Selig1,2, Laura Saager, Klaus Böhme, Bodo Kurz2, and B. Rolauffs1
Presenting Author: Mischa Selig, mischa.selig@uniklinik-freiburg.de
1G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis,...
"Introduction
Patients with chronic kidney disease (CKD) experience multiple comorbidities, among which mineral/bone disorders (MBD) contribute to high mortality due to increased facture risk [1]. CKD affects the quality of bones which become weaker and easily break. Recently, endogenous metabolites, such indoxyl sulfate (IS), were reported to have an active role in the development of uremic...
Introduction: Contemporary reconstructive approaches for critical-sized bone defects carry significant disadvantages. As a result, clinically driven research has focused on the development and translation of alternative therapeutic concepts. Scaffold guided tissue regeneration (SGTR) is an emerging technique to heal critical-sized bone defects. However, issues synchronising scaffold...
Introduction
Cardiovascular diseases remain the leading cause of death worldwide. Our research focuses in building cardiac microtissues that resemble the native heart as closely as possible, in terms of both structure and function. Across its thickness, native myocardium is built of several thin tissue sheaths, and the cardiomyocytes (CMs) in each of the layers are aligned, and thus...
Introduction: Osteochondral (OC) disorders like osteoarthritis (OA) and rheumatoid arthritis (RA) damage the joint's cartilage and subchondral bone. Their treatment remains a significant challenge for both researchers and orthopedics. In vitro models of OC tissue have become an essential tool to help investigate pathogenesis, develop drug screening, and test potential therapeutic approaches....
Introduction: Macrophages are a heterogeneous population of cells. In response to microenvironmental cues macrophages shift their polarization state, alter their phenotype and adopt pro- or anti-inflammatory functions, promoting tissue inflammation or contributing to its resolution. Using a novel high throughput image-based single cell morphology and protein intensity machine learning...
"Introduction Tissue engineering (TE) is an interdisciplinary field that creates functional biologic substitutes for the repair of damaged tissues or organs. One major challenge when generating a functional TE model is its vascularization. Indeed, nutrient and oxygen supply, as well as metabolic waste products collection, are essential for the survival of the engineered tissue after...
The human gut microbiota constitutes the most bountiful and divergent community of organisms compared to the other areas of the body [1]. Growing attention is devoted to the bacterial equilibrium and constitution in human intestines, being highly plastic over time [2,3]. Bacteria present a significant part in response to immunotherapy in cancer [4]. Meanwhile, predominant cell cultures and...
"Introduction: Folding is a crucial process that modulates the function of proteins:[1] non-covalent intramolecular interactions between amino acids give rise to a defined three-dimensional structure with minimal free energy known as protein native state. This is an error prompt process that often results in misfolding and the formation of off-pathway aggregates associated with pathological...
Introduction: Due to their biocompatibility, biodegradability and cell-interactivity, gelatins are widely used in the biomedical and tissue engineering fields. Gelatin can be chemically crosslinked to originate constructs that are stable at body temperature. However, if modified gelatins cannot be produced with consistent molar mass and degree of modification (DoM), these advantageous...
The knee meniscus plays an indispensable role in articular surface protection, shock absorption, and stress transmission. Meniscus injuries are extremely prevalent, with an annual incidence of 66 to 70 per 100,000 people. Due to limited vascularization, the regenerative capacity of the meniscus is relatively low and restricted to the most vascularized outer regions. The most commonly performed...
"Introduction
Layer-by-layer (LbL) coating is a method for surface modification based on the electrostatic interactions between two polyelectrolytes. LbL coatings are used for multiple biomedical applications, because natural polyelectrolytes presenting good biocompatibility can be used for LbL film build-up. It is possible to develop antibacterial surfaces, smart healing materials, and...
Three-dimensional (3D) printing is already routinely used in the clinic, e.g. for pre-operative models or intra-operative guides. However, this does not involve the generation of living 3D structures, i.e., biofabrication of tissues and organs. This automated approach holds potential to advance the field of regenerative medicine as outer shapes can be personalised and organised constructs can...
Mesenchymal stem cells are a promising source for externally grown tissue replacements and patient-specific immunomodulatory treatments. This promise has not yet been fulfilled in part due to production scaling issues and the need to maintain the correct phenotype after re-implantation. One aspect of extracorporeal growth that may be manipulated to optimise cell growth and differentiation is...
Musculoskeletal tissue engineering (MTE) has proven to stimulate survival and differentiation of myoblasts towards tissue regeneration both in vitro and in vivo (1). In this field, different polymeric biomaterials have been employed to provide a biomimetic environment where cells can proliferate and differentiate into muscle tissue.
Polycaprolactone (PCL) is a synthetic aliphatic...
Organ- and tissue-level biological functions are intimately linked to microscale cell-cell interactions and to the overarching tissue architecture. Advances in biofabrication technologies offer unprecedented opportunities to capture salient features of tissue composition and thus guide the maturation of engineered constructs into mimicking functionalities of native organs. Light-based...
Cell morphology plays an important role in controlling cell functions. Application of micropatterned surfaces in cell biology provides reproducible cell morphology and relative stable adhesion and cytoskeleton pattern for investigation of stem cell functions. We have used photo-reactive polymers and UV lithography to prepare micropatterns to control cell size, shape, adhesion area, aspect...
The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have been proposed as a possible therapeutic tool for CNS disorders, namely due to the beneficial actions of their secretome. Indeed, the latter possesses a broad range of neuroregulatory factors that promote an increase in...
T cell activation is modulated by signaling molecules on the surface of antigen-presenting cells (APC); however, in recent years, it has become increasingly clear that cellular forces have a crucial role in T cell activation and subsequent effector responses. Therefore, understanding mechanical modulators is critical in advancing current immunotherapy approaches. To address underlying...
"[Introduction] Extracellular matrix (ECM) plays a critical role in the control of cell adhesion and growth as in vivo scaffold material, therefore the design of ECM-like or ECM-mimicking scaffold has been one of the powerful concepts to provide a successful culture platform for tissue engineering. However, by their molecular size, it has been a challenge to obtain highly purified ECM...
Introduction
There is a dire short of donor corneas for cornea transplantation, leaving millions of visually impaired patients without treatment1. 3D bioprinting holds tremendous potential for fabrication of cornea mimicking structures. One of the key technological challenges in 3D bioprinting is the establishment of bioink compositions that allow both ideal printability as well as...
Various 3D Printing and Bioprinting approaches have proven useful for tissue engineering applications. The achievable spatial resolution of the most widespread technologies, such as for example extrusion, is usually in the range of hundreds of micrometers, limited by the intrinsic attributes of these methods. However, light-based technologies and in particular multiphoton lithography (MPL) can...
"Introduction
In recent years, the clinical application of injectable bone pastes has been increasing because of their benefits including ease to adaptation into irregular-structured defects and injectability suitable to minimally invasive surgery. These advantages are widely advocated to reduce patient complications and health care costs. Here, we successfully developed injectable bone...
Introduction: Mesenchymal stromal cells (MSC)-based therapies for inflammatory diseases rely mainly on the paracrine ability to modulate different cell populations involved in the advance of the disease, such as macrophages. These immune cells possess a broad spectrum of inflammatory responses. In addition, previous data have shown that the MSC secretome influences macrophage phenotype and...
"Introduction
Proteoglycan-4 (PRG4) is a mucinous glycoprotein with critical roles in the bio-lubrication of articular cartilage and joint health1. Intra-articular injection of PRG4 protects against cartilage deterioration in in vivo models of osteoarthritis, an effect that is largely attributed to restored bio-lubrication. Thus far, tissue-engineered, collagen-glycosaminoglycan (coll-GAG)...
Introduction
Infection is the major cause of implant failure after breast reconstruction surgery [1]. Medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of clinically routinely used silicone implants for breast reconstruction [2-3]. Nevertheless, as with any implant, biodegradable scaffolds...
Following spinal cord injury, a complex scar forms around a lesion cavity, preventing axonal regrowth. Despite ongoing development of stem cell treatments for spinal cord injury, effective repair of the cord remains a challenge in part due to the lack of a supportive environment and cell death. Therapeutics that physically bridge the cavity with a neurotrophic environment while simultaneously...
Introduction: Recent bone tissue engineering strategies propose recapitulating the endochondral ossification process for an effective repair. To this end, primary human mesenchymal stromal cells (hMSCs) can be primed in vitro towards hypertrophic cartilage (HyC) formation. While holding promises, limits arise from the performance variability associated with the use of primary cells. Recently,...
"Introduction
Annually, millions of people die because of liver failure, while the waiting duration for a donor liver is around 12 months.[1] Herein, we target hybrid 3D-printed scaffolds to serve liver tissue engineering(LTE) applications.
As starting materials gelatin in combination with a polysaccharide was used to develop printable hydrogels. As polysaccharides dextran (Dex) and...
Since synthetic vascular prosthesis perform poorly in small diameter revascularization, biological vascular substitutes are being developed as an alternative. Although their in vivo results are promising, their productions involve tissue engineering methods that are long, complex and expensive. To overcome these limitations, we propose an innovative approach that combines the human amniotic...
"Introduction
The fabrication of three-dimensional (3D) scaffolds able to promote a spatiotemporal guidance of cell infiltration, vascularization and innervation are of great interest in tissue engineering and regenerative medicine (TERM) applications. To this end, peptide sequences displaying fast and slow proteolytic rates towards urokinase plasminogen activator uPA, namely GTAR and DRIR,...
The exceptional properties of natural structures with density gradients (e.g. bone, sponges, bamboo) have stimulated the interest in reproducing such complex architectures harnessing biopolymer functionality. However, the possibility to generate a hierarchical structure comprising multiple density gradient has not yet demonstrated, mainly due to the lack of technological advancements in...
"Introduction
Bone is a highly dynamic tissue that undergoes continuous remodeling through lifetime. During this process, two cell types, osteoblasts and osteoclasts, are responsible for bone formation and bone resorption respectively. Mechanical stimuli applied on bone tissue can shift the balance between these two cell populations [1]. Different studies have investigated the impact of the...
Introduction: Excessive immune response and development of bacterial infections are two major problems accompanying organ replacement and implant surgeries. Our group aims to develop bioactive coatings to address these issues. Poly(arginine) and hyaluronic acid (PAR/HA) layer-by-layer films are supramolecular thin films (thickness about 1µm) that are easy to build, with promising...
Introduction: The past few years saw an increasing trend in liver disease prevalence [1]. Orthotopic transplantation is the current gold standard treatment. However, its practice is affected by strong complications represented by the paucity of available organs and the necessity of long-term immunosuppressive therapies. Tissue engineering strategies represent suitable alternatives by combining...
Introduction
Multi-Photon Polymerization (MPL) is a Direct Laser Writing (DLW) technique that combines ultrafast (femtosecond, fs) laser pulses and Computer Aided Designs (CADs) for the fabrication of high precision scaffolds that find application in fields such as tissue engineering [1, 2]. We used such scaffolds for mono- and co- cultures of murine N2a neuronal and SW10 glial cells in order...
Peripheral nerve injuries (PNI) affect millions of patients worldwide and cause motor and sensory dysfunction leading to reduced quality of life and increased healthcare costs. The primary treatment option for repairing large PNIs is to use patient’s own nerve graft – an autograft, which is limited by availability and donor site morbidity. In this study, we aim to prepare an off-the-shelf...
"The establishment of vascularisation is one of the current challenges, especially in critically sized bone defects [1,2]. Therefore, the aim of the present work is to develop a biomimetic hydrogel scaffold mimicking the bone osteoid in which proper vasculature is induced in order to maximally stimulate osteogenic regeneration. Thiol-ene step-growth photocrosslinking was herein selected to...
Introduction
While the two most-commonly applied approaches in tissue engineering (TE), namely the scaffold-based and the scaffold-free approach come with individual advantages but also drawbacks, Ovsianikov et al. proposed a third strategy for tissue engineering which combines the advantages of both approaches [1].
We propose here to utilize this third strategy to fabricate millimeter-size...
Introduction
Glioblastoma (GB) is the most frequent and lethal primary brain tumor. GB has currently no cure and the standard care regimens only provide patients a median survival of 12-15 months after diagnosis. Indeed, considering the unfeasibility of performing complete surgical resection and the low efficacy of chemoradiotherapy in eliminating the remaining GB cells, it is not possible to...
Recent progress in 3D bioprinting technologies has shown promising results for the multi-material design of interface tissue engineering. However, the achievement of structural integrity between tissues with different mechanical strengths is a great challenge in the bio-fabrication of tissue interfaces, such as bone-cartilage interfaces1. In this study, we used multimaterial 3D bioprinting...
Introduction
To overcome organ shortage, designers develop engineered livers: devices/methods aiming to temporally assist or permanently replace it. As a complex organ with more than 500 functions, the design of engineered livers is one of the greatest challenges of the field. Since the mid-20th century, multiple pathways have been taken using diverse materials such as charcoal or cells. We...
"Introduction: Osteoinductive bone morphogenetic proteins (BMPs) possess the ability to induce bone formation and therefore have been the basis of osteoinductive devices designed for bone regeneration. Osteogrow C is a novel autologous bone graft substitute comprised of recombinant human Bone Morphogenetic Protein 6 (rhBMP6) within autologous blood coagulum (ABC) with synthetic calcium...
Introduction
Peripheral nerve tissue engineering aims to create biomaterials that can replace and possibly even therapeutically surpass the current gold standard nerve autograft. Tissue-engineered constructs can be designed to deliver a combination of benefits to the regenerating nerve, such as supportive cells, alignment, extracellular matrix, soluble factors, and biomechanical integration....
"Introduction: The Blood-Brain Barrier (BBB) is a dynamic interface which regulates the movement of solutes. The physical barrier consists of endothelial cells (ECs) with extrinsic barrier properties induced by interactions with the neurovascular unit (NVU). Neither static nor dynamic in vitro BBB models fully capture in vivo-like conditions, and while coculturing EC monolayers with other NVU...
"INTRODUCTION
Understanding the interaction between cells and materials is fundamental to tissue engineering. The scientific community's focus on biomaterial-cell interactions has largely fallen on cellular phenotypes, proteins, and nucleic acids, while molecular mechanisms within cells are often overlooked. However, it is expected that cellular metabolism will be significantly influenced by...
Introduction
Bone graft substitutes are typically provided as ceramic granules. Whilst they have undergone successful clinical implementation, they are not without limitations. These include brittleness, variable resorption rates and a lack of control over the microarchitecture, all of which can lead to poor integration of the graft and fibrous tissue formation at the interface. Porous...
"Introduction
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal form of diffuse interstitial lung disease which is associated with substantial mortality and a median survival of 3 years from the time of diagnosis. Acute exacerbations (AE) of IPF have been defined as acute, clinically significant respiratory deterioration of unidentifiable cause. Available data suggest that...
"Introduction: Human umbilical cord blood stored in blood banks cannot always be used for hematopoietic stem cell transplantation as up to 80% of stem cells are lower than the cut-off required for such application, being potentially available for non-transfusion applications such as the source of platelet growth factor [1]. In this study, we fabricated a fibrin-based drug delivery system to...
Introduction
In vitro liver models allow investigation of the cell behavior in disease conditions or in response to changes in the microenvironment and are therefore valuable tools for basic research, drug screenings or toxicological analyses. Mimicking the tissue-level complexity of liver to achieve functional constructs is a major challenge, however, 3D bioprinting technologies open novel...
"Tissue engineering proposes an innovative therapeutic approach to support and induce regenerative processes in damaged tissues. Scaffolds should provide a suitable environment for proliferation, differentiation, and maturation of cells and formation of new tissue and blood vessels. Furthermore, scaffolds should be gradually resorbed at a rate commensurate with bone formation. Calcium...
"Introduction. Extracellular vesicles (EVs) are involved in a plethora of physiological and pathophysiological contexts, and their potential regenerative applications have attracted special interest. Ease of autologous isolation, low immunogenicity and lack of reproductive potential are only some of the enticing characteristics that turn the spotlight increasingly towards EV-based therapy....
Kidney organoid derived from pluripotent stem cells (PSCs) have gradually become a platform to understand kidney morphogenesis, development and diseased states. Despite the abundant differentiation protocols to obtain relevant renal cell types and organoids, most of these only reach a developmental immature stage (1). We hypothesize that the limited maturation is due to absence of relevant ECM...
"Introduction: Spinal cord injury (SCI) is a condition that hampers the communication between the brain and the body, resulting in several comorbidities that decrease the patient’s life quality. The limited regeneration after SCI is mainly attributed to the injury complexity composed of several interconnected mechanisms. Although reestablishment of lost nerve tracts is essential for functional...
Introduction: Mortality caused by liver disease and its complications is on the rise, representing a significant global health issue. Transplantation is the only efficient treatment for end-stage liver disease but is limited by the shortage of organ donors. Bioengineering represents a promising option, with researchers aiming at developing suitable organ replacements for transplantation....
Introduction
Microfluidic droplet-based bioprinting offers several advantages over conventional extrusion-based bioprinting methods such as (i) high-precision spatial patterning of the biologics (including cells, molecules, drugs and bioinks) and (ii) ease of their compartmentalization. These advantages, combined with high reproducibility of the generated microdroplets, facilitate...
"Introduction
Corneal regenerative medicine in recent times has taken a focus on the recapitulation of the limbal epithelial stem cell (LESC) niche. Located peripheral to the central cornea, this pool of stem cells is vital for the preservation of sight throughout adult life. The limbus as an anatomical feature has striking topographical characteristics which are readily observed using...
Introduction: Dynamic culturing systems can overcome challenges of in-vitro fabrication and maintenance of complex 3D tissues, however, the unique physiological conditions to which each tissue is subjected has been hampering noteworthy developments for many engineered tissues. Here we report the in-house development (design, manufacturing, and validation) of a glass slide size microbioreactor...
"Introduction: Growth factors (GFs) are a key component of tissue engineering, but their exogenous administration has proven costly and ineffective. Extracellular matrix-inspired biomaterial approaches have sought to sequester these molecules, regulating their activity and presentation to cell receptors.1 Our previous work has shown that molecularly imprinted nanoparticles (MINPs) can play...
INTRODUCTION. Volumetric bioprinting (VBP) is a recently developed light-based biofabrication method enabling the rapid generation of complex 3D structures within seconds. Short printing times combined with freedom of design allow for the advancement of novel in vitro models and physiologically relevant constructs. However, a more in-depth understanding of the effects of light-based...
"Surgical repair of large skull bone defects is often performed using patient-specific metallic implants.(1) These implants, however, have poor osseointegration ability, and their life-long fixation is dependent on osteosynthesis screws.(2) It is often suggested that a composite model bone graft substitute could be used to overcome these problems, combining desired properties from individual...
Introduction
Severe bone injuries can result in incapacities and thus affect a person's quality of life. Mesenchymal stem cells (MSCs) can be an alternative for bone healing by growing them on scaffolds that provide mechanical signals for differentiation. Such scaffolds can give the appropriate ques to the cells in order to induce their differentiation into mature osteoblasts and later on to...
"INTRODUCTION Therapeutic application of mesenchymal stromal cells (MSCs) has been suggested as a promising regenerative treatment for osteoarthritis (OA) by virtue of their paracrine-mediated chondroprotective and immunomodulatory activity. Nonetheless, collection of MSCs is an invasive procedure and the therapeutic efficacy of autologous MSCs are subject to large variability due to the...
"Extracellular vesicles (EVs) have garnered growing attention as promising acellular tools for bone repair. Epigenetic regulation through histone deacetylase (HDAC) inhibition has been shown to increase differentiation capacity. Although EVs efficacy has been shown, their short half-life in vivo hinders their therapeutic potency. Gelatin methacryloyl (GelMA) hydrogels functionalised with...
The bone is a complex and dynamic tissue, in which the equilibrium between bone deposition and resorption can be perturbed by various pathological conditions, including bone metastases. Against them, no effective therapy has been developed yet, and available treatments are primarily palliative, aiming at restoring bone homeostasis. To improve the process of anti-metastatic drug discovery, new...
"Traditionally, tissue engineering strategies employ a “top-down” approach, where cells are randomly seeded in polymeric scaffolds or hydrogels. As a result, engineered tissues are often at best homogenous in composition, lacking the morphological or structural features of native tissues. Alternative “bottom-up” approaches, that leverage the self-organizing capacity of stem cells, have shown...
"Introduction
Minimally invasive surgery for the restoration of bone tissues lost due to diseases and trauma is preferred to reduce patient complications and health care costs. The current challenge is to design material at the site of surgery with specific behaviors for mimicking the natural structures and delivering appropriate signals to cells promoting tissue repair/regeneration. ...
Bioinspired engineered microenvironments provide cells with a holistic “instructive niche” that offers the adequate entourage for cellular control both in space and time. Biomaterials provides essentially surface signals. We hypothesise that volume characteristics of biomaterials have a negligible influence on cell-behaviour and new tissue formation as compared with interfacial mechanical,...
"Introduction: Large bone defects are a challenge for orthopedic surgeons. BMPs are the most potent bone inductors and accelerators of bone growth. However, poor BMP-2 retention by scaffolds leads to its rapid clearance from implantation sites,1 and thus, require the use of supra-physiological doses. Serious concerns regarding BMP-2-related adverse effects have been reported (including...
Glycosaminoglycans (GAGs) within extracellular matrices (ECM) control the presentation of soluble, cell-instructive signals. The incorporation of GAGs into engineered polymer networks can therefore provide a powerful and versatile means of directing cell fate. We have established a rational design strategy for ECM-inspired hydrogels based on multi-armed poly(ethylene glycol), GAGs of different...
"Development of novel bone biomaterials inevitably has a phase of in vitro testing for cytocompatibility and functional osteogenesis. This relies on defined conditions under which osteoblasts, or their precursors, are stimulated to drive a mature, matrix depositing osteoblast phenotype. Based on the in vitro results obtained, a selection is made to be further tested using in vivo studies....
Human mesenchymal stem/stromal cells (MSCs) are a therapeutically relevant, heterogenous cell entity with immunomodulatory and pro-regenerative potentials. Apparently, MSCs mediate a huge proportion of their therapeutic effects via extracellular vesicles (EVs). Connected to several advantages in using cell-free products for the therapeutic setting, MSC-EVs emerged as promising novel...
"Introduction: Several molecules of natural origin are of great interest to add specific surface functionalities to implant biomaterials: phenolic compounds and keratin can be used for different targets, as an example. They are derived from industrial processing of respectively plants or animals derivatives through a valorization process of waste and a sustainable circular economy approach....
Vasculature plays an essential role in skin physiology and its architecture and function are altered in aged and diseased skin. Quite remarkably, papillary and reticular dermis show very distinct extracellular matrix (ECM) and vascularization. Furthermore, fibroblasts freshly isolated from their native microenvironment have different gene expression patterns, morphology and proliferation rate....
Introduction:
Regenerative Medicine is a relatively new field found at the intersection of science, engineering and medicine. Researchers in this field are traditionally biologists, chemists, materials scientists, data scientists, engineers or physicians who have acquired skills and knowledge beyond their basic training and stepped into the rapidly evolving field of TERM. Many of them,...
Organoids (self-assembled 3D tissue structures from a cluster of cells) can be used for patient-specific drug testing or for the generation of larger tissue constructs, which can in turn be used as implants to restore and/or replace damaged tissue. For cartilage, human chondrocytes, both healthy and diseased (derived from patients with osteoarthritis (OA)), show the potential to self-assemble...
Introduction: Atopic dermatitis (AD) is a chronic inflammatory and common skin disorder that is frequently associated with other atopic diseases such as allergic rhinitis and asthma. The immunopathogenesis of AD is a complex process, as both innate and adaptive immune systems are involved in the development of eczema in those patients. Keratinocytes, mast cells, dendritic cells, and T cells,...
"Introduction
The bone morphogenetic protein-2 (BMP-2) is one of the most potent growth factors for bone repair. In the clinic, BMP-2 is widely used for spinal fusion, particularly in the product called InFUSE Bone Graft® (Medtronic). Despite its strong efficacy, the safety of BMP-2 remains questionable as some treated patients suffer from serious side-effects, such as ectopic bone formation,...
In the last years, the role played by extracellular vesicles (EVs) in inter-cellular and inter-organ communication through the delivery of signal molecules has been revealed and, nowadays, it is considered to be of utmost importance. EVs are secreted by almost all cell types and have an important role in several research fields ranging from oncology to immunology and diagnostics to...
"Introduction. One challenge of developing biomaterials for tissue engineering is the capability to precisely engineer desired properties, while keeping robustness and versatility in the system. Cell-encapsulating hydrogels are used as extracellular matrix mimics for basic study of cell function, high-throughput drug screening, and therapeutic delivery. In their molecular design, the...
Introduction: Bone marrow is one of the most preferable sites for metastasis, but the complicated in vivo metastatic niches make it challenging to study cancer cell colonization. We took a novel approach to establish an in vitro complex bone marrow environment on a dynamic 3D culture system, Bone marrow (BM)-on-chip. With a specific focus on prostate cancer, we designed, fabricated, and...
Introduction:
Stromal vascular fraction (SVF) cells, isolated from adipose tissue are an abundant easily accessible stromal cell source for bone tissue engineering. These characteristics make them a good alternative to bone marrow derived mesenchymal stem cells (BM-MSCs). Previous studies from our group provided a proof-of-concept that Adipose-derived Stromal Cells (ASCs), resulting from the...
"Despite immense interests, growing organoids resembling the human musculoskeletal system (including bone, cartilage, muscle, tendon, ligament) in a petri dish remains a major challenge in front of the tissue engineering and regenerative medicine (TERM) community. Bone is a vital organ that contains billions of bone cells as well as a sophisticated internal architecture across several length...
"Collagen scaffolds are well known for their regenerative potential. However, the relatively poor mechanical properties represent a problem (scaffold deformation, partial collapse of internal open pore structure) for the translation into a clinical setting. In this study, we present a novel approach: A Mechano-Hybrid-Scaffold (MHS) that combines a collagen-based biomaterial with highly aligned...
Intro: Our broader understanding of the immune system's role in determining the success of intrinsic repair mechanisms has led to increased research focus on immunomodulatory therapies1. These therapies could be particularly effective in abnormal fracture healing, where bone tissue engineering has thus far failed to provide safe and reliable clinical therapeutics. While current developments...
"Introduction
Alginate is widely used in the biomedical field, particularly to build three-dimensional (3D) systems with ECM-like properties. Despite being a bio-inert biomaterial, alginate can be chemically modified to promote highly specific cell-ECM interactions[1]. We have shown that molecularly designed alginate 3D matrices recap key features of native ECMs supporting tissue...
Introduction: Human cord blood (CB) represents a rich source of several stem cell (SCs) types including hematopoietic stem and progenitor cells (HSPCs). Thus, clinical application of CB cells has become an alternative for the bone marrow transplantation. However, successful application of CB-HSPCs in adult patients requires the development of effective strategies improving their ex vivo...
Bone organoids are an emerging novel platform to study human bone biology and bone formation. Biofabrication techniques such as extrusion bioprinting have been used to produce mineralized in vitro bone models. However, cell-cell interactions and mineralization rates are influenced by the initial cell printing density [1]. Here, we investigated the effect of cell density on mineral formation,...
Our newly developed self-feeding hydrogels with enzyme-empowered degradation capacity have demonstrated high biological performance in-vitro and in-vivo as a novel self-maintained and biocompatible 3D scaffold1. Photo-crosslinkable platelet lysates (PL)-based hydrogels have exhibited to support distinct human-derived cell cultures owing to their high content of bioactive molecules, such as...
"From a mechanical point of view, bone demonstrates exceptional mechanical properties owing to its complex hierarchical composite structure. The human skeleton acts as a support for the whole body as it withstands stresses produced by daily routines and gravitational force. As a result of these stresses, the bone regulates its geometry and density through activating formation and resorption...
Bone is a complex composite material, so any scaffold or model designed to reconstruct its integrity or model its behaviour must have a high degree of complexity and fulfil several requirements, including high biocompatibility, suitable surface and mechanical properties, adequate architecture, tailored degradability. Obtaining a bone-mimetic composition is also crucial, because hydroxyapatite...
Intramembranous ossification is the most common pathway used in tissue engineering (TE) of bone. However, therapeutic effects in case of large bone defects are suboptimal due to hindered vascularization. On the other hand, TE grafts generated via the endochondral ossification pathway, where the bone formation occurs through cartilage intermediaries, become vascularized and form bone upon...
Design and fabrication of optimal scaffolds for bone tissue repair is a multi-physics problem targeting osteoconductive, biodegradable material designs with loading of necessary growth factors. Therefore optimal tissue regeneration based on accurate analysis models including the degradation behavior of biomaterials is a critical design requirement (Byrne et al., 2007). In order to explore bone...
"Injectable biomaterials for cell and drug delivery is a rapidly expanding field that may revolutionize medical therapies. Here we report on the fabrication of injectable electrospun microscaffolds used to deliver desired cargo through the needle. We observed an efficient attachment of cells to the scaffold's surface, creating cell-populated microscaffolds (MS) that could be injected or 3D...
"INTRODUCTION: Bronchopulmonary Dysplasia (BPD) is a life-threatening disorder affecting premature newborns, for which no definite cure is available1,2. Lung fibrosis is one of the main problems that affect young patients. The aim of this work was to investigate the mechanism of action of human extracellular vesicles (EVs) both in vitro and in an animal model of hyperoxia-induced BPD....
Background:
Urethral reconstruction is performed in patients with urethral strictures or for correction of congenital disorders. In most instances, foreskin or buccal mucosa flaps are used in these surgeries. However, complications may occur due to limited availability of tissue. In the future, tissue engineering (TE) might offer alternative solutions as it enables a detailed design to...
A limitation, when it comes to 3D printed biomimetic structures with micrometer and sub-micrometer precision are computer aided design (CAD) programs. Existing CAD software is usually based on “manual” step-by-step design principles intended and suitable for subtractive and formative manufacturing methods rather than organic designs for additive manufacturing. The resulting structures can...
The components of cellular microenvironments, especially the extracellular matrix (ECM), strongly regulate biological processes through biochemical and mechanical signaling. For this, hydrogels have been widely used to build artificial niches mimicking the native ECM. Strain-promoted azide-alkyne cycloaddition (SPAAC) is a biorthogonal reaction between strained cyclic ring-containing alkynes...
"
3D-printed personalised scaffolds are an attractive approach for mandibular bone repair. Poor mechanical stability of medical grade ceramics is a disadvantage. Also, delivery and retention of regenerative cells within 3D-printed scaffolds remains a challenge. This work aims to create 3D-printed personalised scaffolds based on a novel combination of materials with enhanced mechanical and...
In regenerative medicine, extracellular vesicles (EVs) have been increasingly studied as alternative acellular therapies overcoming the limitations of cell-based strategies. Derived from mineralising osteoblasts, EVs demonstrated their osteogenic potency suggesting their potential as a novel bone regenerative therapy. However, the clinical translation of EVs remains limited by issues...
Introduction
Tendon injuries are common in equine athletes. Tissue healing occurs via biomechanically inferior scar tissue deposition, often resulting in re-injury. This is mediated, in part, by excessive proinflammatory cytokine release in the acute stages following injury. Stimulating equine tenocytes with interleukin 1 beta (IL-1β) alters tendon-associated and extracellular matrix...
Introduction
Autologous bone grafting is currently the gold standard treatment for bone defects. However, it is still associated with multiple drawbacks such as limited availability and donor site morbidity. Various approaches have been explored to overcome this, of which endochondral bone regeneration (EBR) has emerged as a promising approach. EBR aims to mimic the process where bone is...
Cancer, as a cause of death, is only surpassed by cardiovascular diseases. Thus, it is critical to achieve progress in its treatment and prevention. Given the complexity and heterogeneity of cancer, various therapeutic targets are being investigated, including components of the tumor milieu. The tumor microenvironment (TME) consists of several types of cells (vascular cells, tumor-associated...
"Introduction
Most bone defects heal successfully, however, there is an increasing number of cases where bone self-healing is insufficient. Thus, there is a high need for scaffolds able to replace the clinical gold standard treatment autologous bone grafting, which entails donor site morbidity and lacks control over spatial architecture to match defect sites. Biofabrication offers great...
"
Injectable biomaterials have evolved from serving as simple structural fillers to acting as multi-functional systems capable of directing human mesenchymal stromal cell (hMSCs) response. However, the selection of appropriate design parameters for injectable polymeric microbeads for translational applications remains a challenge. We have demonstrated promising strategies to address this need...
Introduction: Fecal incontinence has a high impact on patient quality of life. Available treatments based on surgical and non-surgical approaches range from change in diet, to bowel training or sacral nerve stimulation, none of which represent a long-term solution. Novel therapies are emerging that aim to regenerate the sphincter muscle and, therefore, restore continence. These approaches...
Spinal cord Injury (SCI) is a life changing event with a high number of new cases reported every year. The most common cause of SCI comes from traumatic events, such as traffic accidents, falls, violence and sports activities, while the non-traumatic events (tumours, neurodegenerative and infectious diseases) are less prevalent. The injury incurred in the spinal cord tissue triggers several...
Introduction: Bone remodeling is the combined process of bone resorption by osteoclasts and bone formation by osteoblasts. This process is regulated by mechanosensing osteocytes. It is the most fundamental physiological process that defines living bone. An imbalance in this process can cause metabolic bone diseases such as osteoporosis. Currently, no complete in vitro bone remodeling model is...
Artificial cells have been topic of intensive investigation over the past years. Although in first instance they have been mainly developed as a platform to attain a better fundamental understanding how living cells operate, they have recently also been recognized as interesting structures in biomedical research. In this lecture I will discuss an artificial cell system based on complex...
"Introduction:
Pericytes reside outside of capillary blood vessels. In the brain, pericytes, brain microvascular endothelial cells, and astrocytes form the neurovascular unit (NVU). A normally functioning NVU regulates cerebral blood flow and the permeability of the blood-brain-barrier (BBB). Breakdown of the NVU and dysfunction of the BBB are increasingly recognised early biomarkers of...
STEM CELLS IN BONE REGENERATION, A RANDOMIZED CLINICAL TRIAL
Cecilie Gjerde1, Mariano Sanz2, Markus Rojewski3,4, Pierre Layrolle5, Hubert Schrezenmeier3,4, Kamal Mustafa1
1Institute of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway.
2Department of Dental Clinical Specialities (DECO), Faculty of Odontology, University Complutense of Madrid, Spain
3Institute of...
TBA
My research group is focussed on developing new bioengineering technologies that can provide control over the assembly of biomaterials and tissues. I have a long-standing interest in ultrasound: waves of pressure that can interact with living and non-living matter to instigate a range of chemical, physical, and biological processes. First, I will discuss a technology that uses high-frequency...
"Introduction
Despite the availability of safe and effective vaccines against COVID-19, new variants of concern (VOC) such as Delta and Omicron are emerging. In these surges, governments and institutions around the world urgently need ways to rapidly respond to outbreaks of new VOCs or other infectious respiratory diseases with pandemic potential.
In this context, tissue-engineered...
"Introduction: Craniosynostosis (CS) is a bone developmental condition that affects 1 in 2100 children worldwide, characterised by premature ossification of the cranial sutures. Particularly, non-syndromic-CS (NS-CS) has been associated to microenvironmental causes. However, little is known about the signalling pathways that govern this skull suture premature ossification. Thus, we hypothesize...
Insufficient vascularization is a major obstacle for clinical application of tissue engineered transplants including bone. The ambition is to provide an environment rich in vascular networks to achieve efficient osseointegration and accelerate functional restoration after implantation. Of particular interest is the microvasculature that is crucial for oxygen and nutrient delivery....
Artificial cells are biomimetic systems used to study properties of biological cells and to explore new possible applications in place of biological cells. Tissue engineering aims at replacing or recovering damaged or diseased tissues, or reconstituting tissues in vitro for disease modelling and drug development. Artificial cells can be combined with modern biofabrication strategies like...
Introduction
Nowadays, great attention is devoted to the development of 3D in-vitro neuronal models both for fundamental neuro-mechanobiology applications as well as for disease modelling. Typical approaches include either scaffold-free or scaffold-based strategies. Although the first ones, based on cell self-assembly mechanisms, lead to the formation of tissue-like structures called...
"
Introduction
The intervertebral disc (IVD) distributes multiaxial loads applied to the spine, namely axial compression, tension, lateral bending, and torsion. The effect of mechanical loading on IVD health and degeneration is commonly investigated in bioreactors used for ex vivo culture of IVD organ models. Currently available bioreactors have mainly integrated one or two degrees of...
Macrophages are known as the most dominating cells at the wound site, and they coordinate the transition between tissue repair phases during the entire wound-healing process. Especially, anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To...
The current gold standard for peripheral nerve repair is autograft. However, the low availability of nerves and loss of function at the donor site are the major disadvantages associated with this procedure. Thus, to address the limited regenerative capability of the human nerves, nerve guidance conduits (NGCs) fabricated using biocompatible and biodegradable materials has proven to be a...
Cancer continues to be a leading cause of mortality in modern societies; therefore, improved and more reliable in vitro cancer models are needed to expedite fundamental research and anti-cancer drug development. Here, we describe the use of a miniaturized continuous stirred tank reactor (mCSTR) to first fabricate and mature cancer spheroids (i.e, derived from MCF7 cells, DU145 cells, and a mix...
Background:
Mesenchymal stem cell (MSCs) -based therapy has a promising potential in bone tissue regeneration. Although, growing evidence has suggested that paracrine mechanisms may be involved in the underlying mechanism of MSC transplantation, and extracellular vesicles (EVs) are an important component of this paracrine role. However, information on the influence of different...
Mesenchymal stem/stromal cells (MSCs) are considered a disease-modifying treatment for osteoarthritis (OA). However, the precise molecular mechanisms of actions under which MSCs exert their therapeutic effect have not yet been identified in OA. Since MSCs actively interact with their environment, most likely the inflammatory OA milieu will stimulate their response. To identify these...
Introduction
Plasma cell malignancy - multiple myeloma (MM), occurs primarily in the bone marrow (BM) and appears to be strongly regulated by interactions with BM mesenchymal stromal cells (MSCs). In addition, collagen is an important constituent of the BM environment and provides not only structural, but functional support to many of its cells. Improved understanding of MM pathology requires...
Introduction
Endothelial cells (ECs) have potential in bone tissue engineering due to their important role on vascularization. For repairing bone defects, co-culturing of ECs and bone marrow stem cells (BMSCs) is suggested to induce both the capillary network formation and bone regeneration. The communication between the two cell types has been experimented on settings based on cell number...
"EFFECT OF DIFFERENT LIGHT WAVELENGTHS ON ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM/STROMAL CELLS
Introduction: Treatment of cells with electromagnetic irradiation (light) can affect their proliferation and differentiation ability. Exposure of cells to light sources with different wavelengths (wavelengths around 415 nm/blue, 540 nm/red, and 810 nm/infrared are most common) appears to have...
Introduction
Chronic back and joint pain has been rated as a top risk factor of disability worldwide. In vitro culture of peripheral sensory nerve, namely dorsal root ganglion (DRG) neurons, is a useful model to investigate pain-associated biology and to discover novel regenerative medicine in terms of pain alleviation. Typical monolayer culture of DRG cells, however, losses the multicellular...
"Introduction
The use of human bilayer tissue-engineered skin substitutes (hbTESSs) for the treatment of dermatological pathologies is a promising therapy, especially for severe burn patients where there is a lack of donor tissue and wound healing process is disrupted, increasing risk of infection and mortality. In search of personalized medicine, several hbTESSs are under research; their...
MATRIX-BOUND NANOVESICLES AS SELECTIVE MODULATORS OF THE IMMUNE RESPONSE
Introduction: Matrix bound nanovesicles (MBV) have recently been identified as an inherent component of the extracellular matrix (ECM) and possess the ability to mitigate the proinflammatory activation state of macrophages. While the “anti-inflammatory” properties of MBV have several potential clinical applications, it...
Introduction:
3D in vitro systems are an envisioned alternative to animal models especially in drug testing for research of antitumor treatments (1). Within native tissue microenvironments, the vascular system supports the physiological organ growth with nutrients and growth factors, but also plays important role in pathological conditions such as treatment-resistant tumor progression. Among...
"<div>Introduction. The dermal white adipose tissue (dWAT) is the population of intradermal adipocytes within dermal part of the skin which actively participates in physiological and pathological processes i.e. hair regeneration, thermoregulation, immune response in skin infections and wound healing. Despite the growing interest in this population of adipocytes and identification of their...
INTRODUCTION: Mesenchymal stromal cells (MSC) combined with biphasic calcium phosphate biomaterial (BCP) is a promising clinical strategy to repair and regenerate lost bones [1]. Further, MSC derived extracellular vesicles (MSC:EV) are established factors of paracrine inter-cellular communication with various cell types, including immune cells, which impacts their regenerative potential [2] ....
Purpose/Objectives: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints that affects approximately 7.5 million people worldwide. Disease pathology, while multifactorial in etiology, is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of...
"Introduction
The wide spectrum of brain injuries experienced in neonates and preterm newborns and the potential plasticity of the CNS prompts us to seek solutions in the field of neuroregeneration in this group of patients and to prevent the worst effects of prematurity and perinatal problems. Drug-resistant epilepsy remains one of the biggest problems of prematurity and its consequences....
Epithelial Ovarian cancer (EOC) is the most lethal malignancy in women. Despite de-bulking surgery, chemotherapy and radiotherapy almost 90% of EOC patients will relapse and succumb. One of the main causes of drug resistance and metastasis is the tumor microenvironment (TME) consisting of cancer-associated fibroblasts (CAFs), endothelial cells (ECs), anergic immune cells, adipocyte stem cells...
Introduction. In recent years tumor microenvironment has been recognized as one of the main actors in cancer relapses and metastasis. Indeed, the crosstalk between malignant cells and the niche, as well as the extracellular matrix (ECM) remodeling, not only favor tumor mass growth, but are also preliminary mechanisms to dissemination. These processes have been mainly investigated in tumors of...
Cell-based therapies in the clinic are limited by the number of cells that can be produced quickly and inexpensively. Whereas about one million cells are isolated from a single donor, existing cell-based therapies can require hundreds of millions to billions of cells. Rapid, exponential expansion of cell number would allow faster delivery of life-saving treatments, such as bone marrow...
"Cutaneous chronic wounds are characterized by the absence of healing after six weeks. The classic treatment is the debridement of the wound bed followed by a compression method. When the treatment is not efficient enough, the application of wound dressings is required. To date, no dressings are appropriated to treat the different kinds of wounds. Nowadays, research orientation is towards...
Melt electrowriting (MEW) technique is a manufacturing technology used to fabricate scaffold with user-oriented design. Main distinctive compared to additive manufacturing technique is its ability to fabricate the diameter of few micrometers to sub micrometers range while maintaining high surface to volume ratio. However, this technique has certain drawbacks, such as inaccurate large volume...
Introduction. Matrix-bound nanovesicles (MBV) are nanometer-scale extracellular vesicles secreted by cells and found embedded within the extracellular matrix (ECM)[1]. MBV are similar to exosomes in size and shape, but MBV have distinctly different lipid profiles and RNA cargo[2]. MBV have demonstrated the ability to induce an M2-like pro-healing macrophage phenotype, promote neuronal stem...
Introduction: Adipose tissue-derived stem cells (ATSCs) have been used as an alternative to bone marrow mesenchymal stem cells (BMSCs) for bone tissue engineering. However, several studies have reported that the efficacy of ATSCs in bone regeneration in comparison with BMSCs remains inferior 1,2. The aim of this study was to investigate the mechanism underlying differences in ATSCs versus...
Introduction: Dystrophic epidermolysis bullosa (DEB) is a genodermatosis caused by mutations in the COL7A1 gene, in which patients exhibit mechanically fragile skin (1). The underlying mutation determines the clinical phenotype, which can range from a severe condition characterized by widespread blistering associated with the development of chronic wounds-RDEB (recessive subtype) - to a...
Introduction
Within the scope of personalised healthcare in the field of regenerative medicine, patient-derived cells are key players. Their successful application is, however, often hampered by low cell numbers at the expense of donor-site morbidity and lengthy in vitro expansion. Novel biofabrication methods requiring lower initial cell numbers are therefore timely to address this unmet...
Introduction
Mesenchymal stem cells (MSC) regulate their behavior by sensing mechano-environmental factors.
Accumulated evidence indicates that appropriate mechanical force including fluid shear stress enhances the osteogenic property of MSC on 3D polymeric scaffolds even without the presence of osteogenic cocktail (i.e., dexamethasone and beta-glycerophosphate). However, despite a common...
"Introduction: Mesenchymal stem cells (MSCs) can improve chronic wound healing, and recently it was suggested that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells. However, MSCs still are not the standard of care in wound healing due to several limitations such as patient-specific difference in MSCs, poor survival of...
"PLATELET-DERIVED EXTRACELLULAR VESICLES SHOW THERAPEUTIC EFFECTS ON A 3D TENDON DISEASE MODEL
Ana Luísa Graça1,2, Rui M. A. Domingues1,2, Isabel Calejo1,2, Manuel Gómez-Florit1,2 and Manuela E. Gomes1,2
13B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue...
"<div>Endochondral bone regeneration (EBR) recapitulates natural development of long bones during embryogenesis and fracture repair through implantation of a cartilaginous template into a defect, which is eventually remodeled into bone. Typically, autologous multipotent mesenchymal stromal cells (MSCs) are exploited to generate such cartilage constructs. However, the use of patient-own cells...
Engineered materials that integrate advances in polymer chemistry, nanotechnology, and biological sciences have the potential to create powerful medical
therapies. Dr. Khademhosseini is interested in developing ‘personalized’ solutions that utilize micro- and nanoscale technolgoies to enable a range of therapies for organ failure, cardiovascular disease and cancer.In enabling this vision he...
In this presentation the latest advances in the field of biomaterials for tendon repair will be presented. Current technologies put forward for engineering tendon tissue will be discussed. The focus of the presentation will be on the latest developments in electrospun based scaffolds exhibiting suitable time dependant mechanical properties, nanoscale (fibrous) topography and the ability to...
"Regenerative implants are most ideally suited for individualized production using additive manufacturing. For regulatory market access, if not containing cells or tissue compounds making them ATMP’s, the choice is between serially produced scaffolds, patient-adapted designs or custom-made devices that require a prescription. While it seems helpful that custom-made products do not get a CE...
Modular tissue-engineering approaches provide a promising strategy for building complex living structures from the bottom-up, through the co-assembly of microscale tissue units. Using biofabrication tools, multiple modular units of parenchymal, stromal, and vascular tissues can be rationally combined to recreate structurally/functionally different compartments of human organs. Microtissue...
Introduction:
Injectability is one of the most desirable features of biomaterials. The combination of injectability and photocuring can provide materials to be easily and safely delivered using minimally invasive procedures. This is especially important for tissue sealants which allow to exclude the use of sutures or staples or for patches supporting the weakened tissue. Therefore, the aim of...
Intravital microscopy (IVM) has revolutionized our understanding of single-cell behavior in complex tissues by enabling real-time observation of molecular and cellular processes in their natural environment. In preclinical research, IVM has emerged as a standard tool for mechanistic studies of therapy response and the rational design of new treatment strategies. For understanding immune...
Introduction: Vascular grafts are implanted daily, whether it is as leg or coronary bypasses or as arteriovenous shunts. Autologous blood vessels are the gold standard but have limited availability while synthetic materials are prone to thrombosis, intimal hyperplasia and infections. To overcome these limitations, our team produced a biological Tissue-Engineered Vascular Graft (TEVG) woven...
Cell encapsulation in biomaterial microcompartments is a useful tool to deliver protected cell cargo into defective tissues. However, the processing of micrometric structures is often dependent on the use of typical emulsion agents, including oils and organic solvents. Those are often related with poor cell viability, or require complicated washing procedures to retrieve oil-free cell-laden...
"Epithelial-to-mesenchymal transition (EMT) is a key event in embryo development and post-natal life in which epithelial cells undergo to a transdifferentiation into mesenchymal cells by acquiring a mobile state. This cell transitioning process recognizes the activation of signaling pathways which occur under controlled environments in response to factors controlling stem cell epigenetic...
"Introduction
The aim of this research was to design and obtain an injectable thermosensitive hydrogel consisting of methylcellulose (MC) and agarose which would serve as a smart scaffold for tissue engineering applications. The MC provides thermal sensitivity, while heated up to c.a. 37 ℃ becoming a physically crosslinked hydrogel. While agarose enhances crosslinking of MC rate and increases...
Medical additive manufacturing (aka medical 3d-printing) has received increasing attention in the past years with research applications in many clinical domains, particularly in surgical disciplines (e.g. orthopedic, oral, cardiovascular). In some domains medical 3d-printing has established itself in daily clinical practice, however the question remains if is it ready for broad clinical use....
INTRODUCTION:
Transplantation of non-autologous β-cells is currently regarded as a promising therapy for the treatment of type 1 diabetes, caused by massive β-cell destruction, consequently resulting in insulin shortage. To evade the host’s immune responses, new materials are being developed to encapsulate and shield implanted β-cells. Several immunoprotective material formulations have been...
In this study, fluorescence lifetime imaging of NAD(P)H-based cellular autofluorescence is applied as a non-invasive modality to classify two contrasting states of human macrophages by proxy of their governing metabolic state. Macrophages were obtained from human blood-circulating monocytes, polarised using established treatments, and metabolically challenged using small molecules to validate...
"Following ECM pathological remodelling, the aberrant activation of the mechanosensing apparatus contributes to the establishment and progression of age-related pathologies, like those affecting the cardiovascular system, and cancer. The mechanical turmoil associated with ECM remodeling is known to determine opposite consequences in rather different cell types, like cardiac and tumor cells:...
Introduction
Additive manufacturing approaches have the potential to address a number of major challenges in the field of meniscus tissue engineering (TE), in particular the development of anatomically defined grafts with a spatial architecture and composition mimetic of the native tissue. Here, we report a novel method to engineer organized soft tissues, with a collagen architecture and...
"Introduction:
Human Mesenchymal stromal cells (hMSC) are appealing candidates for regenerative medicine applications. However, upon implantation, they encounter an ischemic microenvironment depleted of oxygen and nutrients responsible for their massive death post-transplantation, a major roadblock to successful clinical therapies. To date, various approaches have been proposed to address...
Symbrachydactyly is a rare congenital upper limb anomaly, that occurs in 1/30,000- 1/40,000 live births resulting in children born with short boneless fingers. Nowadays, these pediatric patients are treated with phalangeal bone transfer from the foot. However, morbidities are occurring at the donor site which result in unstable toes with significant disfigurations that worsen with the child...
"Objectives
The damaged nervous system leads to the impairment of the motor, sensory and autonomic functions, since the central nervous system (CNS) regeneration is very limited. Failure of axon regeneration in the CNS is partly due to the inhibitory environment, and partly due to the intrinsic loss of regenerative ability with neuronal maturation. A key molecule for promoting migration and...
INTRODUCTION
The role of gut microbiota in neurodegeneration is becoming a very interesting topic nowadays, and innovative in vitro and in vivo tools are becoming increasingly a need to help in dissecting the biochemical pathways involved in microbiota-brain interaction. An innovative engineered multiorgan-on-a-chip platform able not only to mimic microbiota-gut-brain connection but also to...
"Introduction. Despite being the youngest branch of regenerative medicine, neural tissue engineering has rapidly developed, with numerous advances close to clinical translation. One of the most researched areas are tissue engineering and regenerative medicine approaches for brain repair after ischaemic stroke, with more than 70 preclinical studies testing therapeutic combinations of...
"Background and Aims: Cholangiocarcinoma (CCA) is a highly aggressive tumor which arises from the biliary duct epithelium. Currently available models fail to recapitulate the full complexity of CCA, particularly the desmoplastic environment and the interplay between cancer cells and the extracellular matrix (ECM). We aimed to create an improved 3D in vitro model by combining patient-derived...
Introduction:
Melt Electrowriting (MEW) is a novel 3D printing method that allows fabricating scaffolds with different designs, including structural gradients. The gradient scaffolds can be useful, for example, in the engineering of tissue interfaces, which are characterized by gradually changing mechanical and biological properties [1]. Nonetheless, the prediction of such scaffolds’...
"Introduction
Multicellular spheroids can be a powerful model mimicking the physiological environment of the tissue in a microscale format. They are often seen as ‘microscale-bioreactors’ providing an appropriate environment for cell differentiation and stem and cancer cell niche, which makes them important for physiological studies and biofabrication. However, this advantage becomes a...
The poor healing ability of tendons as well as the limitations of currently used therapies have motivated tissue engineering (TE) strategies to develop living tendon substitutes. At the same time, the significant lack of knowledge on tendon homeostasis and disease mechanism trigger our interest to focus on the development of adequate 3D tissue models that can provide important insights for...
Introduction:
Axial vascularisation of tissue constructs is essential to maintain an adequate blood supply for a stable regeneration of clinically relevant 3D tissues. In the last 10 years, our research group has been investigating the efficacy of the arterio-venous loop (AV loop) as a model of axial vascularisation. The versatility of the AV loop could be demonstrated in various small and...
"Adhesive biomaterials have been studied by the scientific community in an attempt to surpass the current disadvantages of sutures and staples in surgery, such as the challenging implementation in some tissues and the risk of infection. The developed bioadhesives have been used as: i) glues for maintaining biological tissues together after laceration; ii) tissue sealants for preventing the...
Introduction
Spinal cord injury (SCI) induces paralysis by severing the long axons of neurons and recovery is inhibited by poor regrowth rates. As neural cells are electroactive, electrical stimulation (ES) may present a promising method of promoting axonal regrowth when applied in conjunction with electroconductive (EC) biomaterials1. To efficiently deliver ES to regrowing motor and sensory...
"Cardiovascular diseases (CVD) remain as the leading cause of death worldwide, and there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. While recent technologies provide some insight into how human CVDs can be modelled in vitro, they may not always give a comprehensive...
Inner ear disorders (e.g., hearing loss) are common, but it is difficult to develop a therapeutic drug and to find a specific mechanism because of a lack of the research platforms. Inner ear organoids (IEO) are perceiving as an innovative research platform to reproduce the complex inner ear systems and to solve the previous problems. To improve uniformity and reproducibility of IEO, we develop...
"Introduction. Breast cancer is considered nowadays the most common cause of death for female population. Since traditional treatments (e.g., chemotherapy, radiotherapy, surgery) showed several drawbacks [1], Drug Delivery Systems (DDS) recently gained interest due to the possibility to release therapeutic agents locally and controllably in targeted sites. Herein, we aimed to develop stable...
Introduction
Kidney failure happens due to two conditions; acute kidney injury (AKI) and chronic kidney disease (CKD). These lead to the deterioration of the glomerulus, the filtering unit in the kidney, leading ultimately to end-stage renal failure (ESRF). [1] Current treatments for ESRF, haemodialysis and kidney transplantation are inadequate since haemodialysis replaces filtration but not...
Introduction
Advanced in vitro models (e.g., organoids) are three-dimensional (3D) constructs usually generated from cells with a degree of stemness. This, accompanied by the multiplicity of parameters which condition organoid growth and morphology, results in constructs of different shapes and size and thereby functional properties. To date, a quantitative framework for robust measurement...
"Introduction: MicroRNAs are short, non-coding RNA sequences with the ability to inhibit the expression of a target mRNA at the transcriptional level. MiRNAs are involved in the regulation and modulation of both regenerative and degenerative processes, playing crucial regulatory roles in tissue healing and regeneration. This particular feature makes this family of molecules a very interesting...
Combining different materials or material-properties in 3D printing is garnering widespread attention due to the wide range of possibilities that it provides to produce parts which are more functional and have improved properties. This paper presents the combination of lithography-based ceramic manufacturing, a vat photopolymerization technology capable of realizing high resolution 3D printing...
"Introduction: An abundant and important receptor that regulates numerous ECM-cell interactions is the integrin receptor. To illustrate, integrins influence the cells’ polarity by controlling the apical-basal orientation. Kidney epithelial cells and intestinal organoids cultured in suspension and thus in the absence of matrix, invert the direction of their polarization, with an apical membrane...
"Title: Electrospun silica nanofibres as multifunctional substrate for drug delivery and tissue regeneration
Introduction: Over the last two decades, electrospun nanofibres were demonstrated to be interesting material applicable in regenerative medicine and drug delivery, possessing number of unique properties including high specific surface area, high porosity and small pore size....
Introduction
Neurodegenerative diseases (NDs) are a group of chronic disorders (e.g. Alzheimer’s disease, Parkinson’s disease and multiple sclerosis -MS) characterized by progressive neurological dysfunction. Despite different neuronal populations can be affected, NDs share major clinical manifestations, namely motor impairment, cognitive disability and/or dementia. Effective treatments do...
"Background and Aims:
Biliary complications that may arise after liver transplantation, such as non-anastomotic strictures and diffuse bile leakage, are challenging and complex. Ischemia-related cell death and impaired regeneration of damaged biliary epithelium is known to be involved in causing these complications. Intrahepatic cholangiocyte organoids (ICO) allow for the expansion and study...
Additive manufacturing allows for a wide range of freeform and complex shapes to be made with little or no manufacturing limitations. The most significant benefit of additive manufacturing in medical applications is that it allows for the creation of patient-specific medical products such as implants. Individualized implants are considered to provide greater comfort, precise fit, user...
Tendon/ligament injuries are a relevant clinical problem in modern society. Although these tissues can selfheal when a lesion occurs, the complete functional recovery is difficult to achieve due to their low cellularity and vascularity. Moreover, reconstruction strategies have a non-negligible failure rate [1]. Failures often occur at the enthesis, the tendon/ligament-bone insertion [2]. This...
"INTRODUCTION: Collagen I has been the gold standard material to generate many in vitro tissue models, including organotypic skin [1]. The rate of collagen remodeling by fibroblasts incorporated in the dermal part of the model, leads to significant dimensional changes during its development, which can be associated to additional hurdles when cultured within dynamic culture systems. These ones,...
"Introduction: Tendinopathies are one of the most common musculoskeletal conditions. Unsatisfactory healing has a significant impact on the life of patients and imposes a remarkable socioeconomic burden. The recovery from tendon injuries is slow and requires extensive rehabilitation. The resulting scar tissue lacks the mechanical integrity of the original tissue, and therefore complete...
"Possible biomarkers to predict the risk of healing delays are of huge clinical interest since 10% of fracture patients progress to delayed or non-union of fractures [1]. During endochondral ossification, which takes place in mechanically unstable regions with higher risk for delayed fracture healing, the bone regenerates through chondrogenic differentiation leading to a cartilage tissue...
Introduction: Lasers have been used for years in the field of cancer therapy. Nanosecond pulsed lasers, in particular, have been used in the generation of reactive oxygen species via plasma for the triggering of immunogenic cell death[1][2], for the delivery of biomolecules intracellularly via optoporation[3] and for tumor resection[4]. Notwithstanding this large range of uses, the full impact...
"INTRODUCTION
The regenerative effect of Platelet Rich Plasma on skin and other tissue lesions is well known. If, on the one hand, research aims to optimize PRP standardized protocols, on the other hand, it aims to identify substrates as vehicles for the platelet content release to the lesion site. For the latter purpose, hyaluronic acid (HA) is proposed thanks to its viscoelastic and...
"Introduction
linical translation of tissue engineering-based therapies is currently limited by the difficulty in inducing essential vascularisation for tissue viability after transplantation. Thick and metabolically demanding engineered tissues require a defined microvascular network to provide sufficient nutrient and gas exchange. Laser ablation has emerged as a promising technology to...
Current medical devices certification is challenging due to the update in the regulatory norms and the appearance of gaps (grey zone) due to advances in both the materials and the fabrication technology. A key aspect when reaching a higher level of technology readiness is to have a comprehensive view of the entire process that will lead to the conformity of the devise with the medical device...
Organoids, 3D multicellular aggregates, provides excellent possibilities to recapitulate pato/physiological properties of human tissues or organs. Methodological obstacles lie in uniform formation, differentiation and long-term cultivation. Preparation and maintenance of organoids can be labor-intensive, medium exchange is usually discontinuous, and individual organoids are highly heterogenous...
"The development of regenerative therapies for the intervertebral disc (IVD) is of much interest because IVD degeneration is a major cause of low back pain, one of the leading causes of disability worldwide. The most common approaches are to utilize biomaterials, cells, and/or molecular agents, alone or in combination. Some of these approaches are moving toward clinical implementation and have...
In this talk, author's decades-long research on inducing bone from adipose stem cell (ASCs) will be introduced, including 1) the exploration of osteogenic potentioal of ASCs versus bone marrow stem cell (BMSCs), 2) investigation of small molecules, peptides, gene transfer to enhance osteogesis, 3) synergistic effect of coculture of ASCs and BMSvs in osteogenesis and angiogenesis, 4) mining of...
Nanotechnology is now found in almost every aspect in life, from the liposomes that carry COVID-19 vaccines to coatings placed on floors to reduce wear. Over the past 20 years, the use of nanotechnology in medicine has grown from the unknown to now significantly helping to prevent, diagnosis, and treat numerous diseases. This is true for regenerative medicine and tissue engineering as well....
Biomanufacturing cells and tissues from human pluripotent stem cells (hPSCs) typically strives to guide differentiation through developmentally relevant pathways in a well-defined, dynamic bioreactor environment. While great strides have been made in differentiating hPSCs to many somatic cell types, robust biomanufacturing remains a roadblock to clinical progress of hPSC-derived cell and...
The natural extracellular matrix (ECM) is a highly dynamic, supramolecular structure composed of various bioactive molecules held together by specific interactions. The ECM directly interacts with cells and dictates cell behavior to a large extend. Our goal is to synthetically mimic this intricate natural system using supramolecular materials based on hydrogen bonding units. The dynamics of...
Therapeutic angiogenesis, i.e. the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue-engineered constructs and to treat ischemic conditions. Vascular Endothelial Growth Factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth, as well as non-vascular side-effects....
Impaired tendon function leads to pain and restricted movement of the joints. This impairment can be due to the degeneration of the tendon and, in the worst-case, due to rupture. Conservative and surgical treatments are available, however treatment duration can be long and the failure rate is high. In order to develop new treatment strategies, a better understanding of the processes underlying...
This lecture will show how biomaterials and components of the extracellular matrix, i.e. structural proteins and growth factors, affect the osteogenic potential of human adipose-derived mesenchymal stromal cells (ASC). Examples of bone formation by various human adipose derived cells-based engineered matrix/tissue, via either intramembranous or endochondral ossification will be presented. The...
"Low back pain is the leading cause of morbidity worldwide and yet most therapies fail to target the cause and are purely symptomatic or end stage surgical options. Intervertebral disc degeneration is associated with approximately 40% of low back pain cases and thus a target for potential regeneration. Intervertebral disc degeneration is a catabolic process caused by altered cell behaviour and...
"ENGINEERING HIGH DENSITY CAPILLARY-LIKE NETWORKS USING MICROPOROUS ANNEALED PARTICLE TISSUES
M.R. Schot1, C.A. Paggi1, M.L. Becker1, J. Leijten1
Presenting author: Maik Schot, m.r.schot@utwente.nl
1Department of Developmental BioEngineering, TechMed Centre, University of Twente, the Netherlands
INTRODUCTION: The vascular tree is essential for the function and survival of tissues....
"Tendon disorders and injuries are one of the most common musculoskeletal disorders. Our knowledge of the causes and underlying mechanisms for the development of tendinopathies still remain fragmentary. Recent evidence has clearly implicated the presence of immune cells during early tendinopathy and we are beginning to better understand the origin and properties of these cells. Recently, we...
Human induced pluripotent stem cell (hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine, however, there remains a requirement to refine the biophysical and biochemical parameters that govern kidney organoid formation. Here we describe the differention and maturation of hiPSC-derived kidney organoids within fully synthetic...
Synthetic hydroxyapatite is therapeutically used as bone graft substitute, bone filler, or as coatings to support attachment of bone to metal implants. Here I will present some data on how our group have used hydroxyapatite nanoparticles in combination with various polymers and fabrication techniques to support bone cell differentiation and matrix formation in both static and mechanically...
"Introduction. Coupling of angiogenesis and osteogenesis is crucial to generate vascularized bone grafts. Semaphorin 3a (Sema3a) regulates osteoblasts and osteoclasts to promote bone synthesis through Neuropilin-1 receptor (NP1). We previously found that: 1) short-term delivery of Vascular Endothelial Growth Factor (VEGF) in osteogenic grafts dose-dependently decreases bone formation by...
"Introduction
The ultimate goal in vascular tissue engineering is the generation of bioartificial blood vessels that resemble the morphology and function of native vessels as accurately as possible. Previous studies have shown that the tunica intima and tunica media of native blood vessels can be resembled in bioartificial vessels by applying physiological mechanical stimulation using...
"Over 300 million cases of osteoarthritis were reported in 2017, stating one of the most prevalent chronic joint diseases worldwide characterized predominantly by long-term progressive cartilage and subchondral bone degeneration. Conventional therapy approaches utilize pharmacotherapy mostly for pain relief and at end stage disease treated by whole joint replacement surgery to retrieve some...
"Introduction
Efficient regeneration of different tissue types requires solutions that are specifically tailored to meet certain criteria. This is particularly true for the group of hard-to-regenerate tissues, such as cardiac, neural or chondral, which are known to have a low self-regeneration potential. The cells of these tissues often require certain factors to induce their division,...
"Introduction
Patients requiring soft tissue reconstruction caused by defects or pathology may require biomaterials that provide a void volume for subsequent vascularization and new tissue formation, as autografts are not always a viable option. Here supramolecular hydrogels represent promising candidates due to their 3D structure being similar to the native extracellular matrix and their...
Objectives
The glucocorticoid receptor (GR) is a nuclear receptor that controls critical biological processes by regulating the transcription of specific genes. GR transcriptional activity is modulated by a series of ligand and coenzymes, where a ligand can act as an agonist or antagonist. GR agonists, such as the glucocorticoids dexamethasone (DEX) and prednisolone, are widely prescribed...
"Introduction
Tendon injuries occur commonly in human and equine athletes. Post-injury, the healing response is inadequate leading to increased deposition of scar-tissue and high re-injury rates. This has motivated the development of novel treatments which promote superior tissue regeneration. Particular interest has surrounded the use of bone-marrow mesenchymal stromal cells (BM-MSCs), with...
"Introduction
Low back pain due to intervertebral disc (IVD) degeneration is a major health and socioeconomic problem throughout the world. In the young and healthy IVD, large and vacuolated notochordal cells (NCs) are present1. These cells are, in some species (e.g. humans and dogs), replaced by chondrocyte-like nucleus pulposus cells (NPCs) during maturation and ageing2. In previous...
"Introduction: Progenitor cells from the periosteum are major contributors in fracture healing with contribution to the formation of the cartilaginous fracture callus. It was previously demonstrated that microspheroids of human periosteum derived cells, differentiated towards the chondrogenic lineage, could be assembled into scaffold-free constructs that healed murine critical-size long bone...
"Introduction: Vascularization is crucial for proper implant survival and integration in the body. For an implant to be vascularized in vivo and thereby supplied with oxygen and the needed nutrients, the body’s blood vessels have to invade the implant first. This is a very slow and often insufficient process, especially in thicker tissues, which can result in implant loss. A solution for this...
"Despite the high incidence of tendon injuries globally, an optimal treatment strategy has yet to be defined1. A key challenge for tendon repair is the alignment of the repaired matrix into orientations which provide maximal mechanical strength2, 3. Using oriented implants for tissue growth combined with either exogenous or endogenous stem cells may provide a solution. Previous research has...
"Introduction
The last decade, efforts have been made in developing more effective diagnostics for low back pain. The focus was addressed towards Modic Changes (MCs), pathological signal intensity changes in the vertebral bone marrow and endplates of the intervertebral disc (IVD), which can be detected on Magnetic Resonance Imaging (MRI)1. In contrast to the human situation, little is known...
The use of mesenchymal stem cells (MSCs) for bone regeneration is a promising alternative to conventional bone grafts. Because local metabolic alterations seem to be critical for bone regeneration, metabolomics (through cell extracts and culture media) may unveil novel information on MSCs osteogenic differentiation,1,2 allowing their behaviour to be understood and potentially guided towards...
"Introduction
In situ tissue-engineered vascular grafts (TEVGs) based on resorbable synthetic scaffolds have the potential to overcome the limitations of prosthetic graft replacement and provide off-the-shelf availability. Despite massive efforts in investigating new materials, up to date no TEVG is clinically available. One of the most important challenges for successful regeneration is to...
"After decades of cutting-edge academic work, novel electrospun biomaterials are finally starting to enter clinics and patients worldwide. The process of taking an electrospun material from the lab, to the clinic, and finally to market is long and difficult. It requires the collaboration of many professionals over the course of years. But what it creates are world-class, ground-breaking...
"INTRODUCTION: The use of biomaterials inside the body always entails the risk of infection. This risk might even be higher in in situ tissue engineering applications. Since the porous scaffold materials can form a niche for invading bacteria, the intended in situ production of novel tissue may be severely compromised by infection. Therefore, we aim to develop a new polymeric supramolecular...
"Introduction: Low back pain (LBP) is a leading cause of disability worldwide and intervertebral disc (IVD) degeneration (IVDD) is a major contributor of LBP1. The IVDD is accompanied and often preceded by the replacement of large vacuolated nucleus pulposus cells (NPCs) by non-vacuolated, clustered cells in the notochordal cells (NCs) of the IVD2. The iPSpine project aims to re-populate the...
"INTRODUCTION:
In the field of bioprinting, which is growing very rapidly, the bioextrusion technology represents more than 80% of the market. The other technologies (e.g. microvalve or inkjet) are used for their ability to print droplets. Among them, laser-assisted bioprinting (LAB) represents the most advanced technology to achieve high resolution printing and high cell viability [1][2]....
"A well-balanced shift from pro- to anti-inflammatory processes during healing appears essential for successful regeneration and may prevent from chronic diseases or tissue damage. Resolution of inflammation is an active process, which is regulated by specialized pro-resolving mediators (SPMs) such as lipoxins, annexins, and resolvins. The contribution of these mediators to the severity of...
"Introduction: The lack of functional vascular networks is one of the most important hurdles in tissue engineering, limiting the obtainment of fully functional organs substitutes. Vascularization promotes efficient nutrients and oxygen supply, representing a key factor for in vivo application [1]. Endothelial cells not only act as the structural building blocks of vascular endothelium, but...
Introduction: Allograft vasculopathy is an aggressive form of accelerated atherosclerosis that manifests uniquely in transplanted hearts, lungs, and kidneys. Activated blood vessel endothelial cells (ECs) stimulate alloreactive CD4+ and CD8+ T-lymphocytes to result in sustained inflammation. Transition metal carbides, MXenes, are an emerging class of nanomaterials that have recently been shown...
Mesenchymal stem cells (MSCs) are in the frontline of tissue engineering and regenerative medicine because they have indefinite self-renewal potential, and also exhibit great multilineage differentiation into a variety of tissues such as such as bone, cartilage, and adipose1. In the field of bone tissue engineering, the osteogenesis of MSCs is a promising therapeutic target, and controlling...
Introduction
Spinal cord injury (SCI) is a devastating condition that disrupts both sensory and motor function, with very limited prospects of functional recovery. Electrical stimulation (ES) has become a common clinical remedy to lessen the impact of SCI-induced pain after injury. However, regeneration-focused lesion site electrostimulation has not had clinical translation yet, despite...
Introduction: Lack of sufficient vascularization to support cell viability, growth and function in scaffold guided tissue regeneration (SGTR) is a prevalent challenge facing tissue engineering today. Matching axial vascularization is a regenerative therapeutic approach which incorporates the benefits of flap-based techniques for neo-vascularization to further aid tissue regeneration....
"Introduction: For a viable and compliant clinical translation of tissue-engineered products, the adoption of automated technologies has been acknowledged as a prerequisite. Recently, the use of chondrogenic microtissue and organoid assemblies has shown promising results in long-bone defect regeneration through endochondral ossification[1]. Hence, automated biomanufacturing technologies able...
INTRODUCTION
Tendon tissues host different cell populations that play important roles in their physiology and pathophysiology. A hallmark of tendon injuries and diseases is the persistent inflammatory response that can self-amplify and lead to chronicity. The inflammatory phase of tendinopathy is characterized by increased vascularization and influx of immune cells (mast cells, macrophages, T...
"Introduction
One of the key challenges in the field of tissue engineering is the vascularization of tissue-engineered constructs. Until now, endothelial cells (ECs) derived from human umbilical cord have been the predominant EC type for the engineering of vascularized tissue. However, ECs of different origins display a great heterogeneity, reflecting in tissue- and organ-specific...
"INTRODUCTION
Current treatments for oesophageal cancer and oesophageal atresia, that involves the repair of the entire thickness of the oesophagus, present various complications and challenges due to the lack of functional oesophageal replacement tissue. Through the combination of cells, scaffolds and biologically active molecules, tissue engineering presents an innovative approach to...
"Back pain is often associated with intervertebral disc (IVD) degeneration. Beside surgery, novel treatments relying on stem cell injection have been tested. Unfortunately, the outcomes are disappointing because of cell leakage and incomplete differentiation. Nowadays, a consensus exists on the necessity to encapsulate stem cells within a hydrogel to maintain them in situ and favor their...
"Vasculature plays an essential role in skin physiology and its architecture and function are altered in aged and diseased skin. There is thus a need to develop innovative 3D in vitro models with adjustable and amenable vasculature. Several in vitro skin models co-seeding endothelial cells with fibroblasts and keratinocytes have been proposed using scaffolds or bioprinting. However, they all...
"Introduction
Delayed or severed tissue regeneration is often caused by dysfunctional immune system.[1] One solution to tackle this issue is to design immunomodulatory materials that support tissue regeneration by priming immune system to a pro-regenerative state.[2] For example, it is known that high molecular weight (>1000 kDa) hyaluronic acid (HA) can polarize macrophages to an M2...
Loss of large, vacuolated notochordal cells (NCs) from the human intervertebral disc (IVD) is thought to initiate degeneration and associated back pain. It is therefore hypothesised that implantation of NCs may halt or reverse degeneration and thus relieve back pain. However, NCs are lost in early childhood, therefore iPSCs differentiation to NCs offers a clinically-viable cell source. Here we...
"Cartilage microtissues are promising tissue modules for bottom up biofabrication of implants leading to bone defect regeneration. Most of the protocols for the development of these cartilaginous microtissues have been carried out in static setups, however in order to further achieve higher scales suspension process needs to be investigated. In the present study we explored the impact of...
Introduction:
Lack of a cornea’s donor is still a huge problem in ophthalmology leaving over 98% of people waiting for the transplantation. As the solution, bioengineered scaffolds, mimicking the fibrous structure of the corneal stroma are proposed. To obtain a full regeneration, such substrates should provide both cornea cells repopulation and optical transparency. In the native cornea, the...
3D culture and organoid technologies have been developing rapidly in the last decade, and already found widespread applications in biology and medicine. While cells, and stem cells in particular, have tremendous self-organization potential, most applications benefit from further engineering of the cellular microenvironment in order to guide the morphogenesis.
We will describe several...
Recent efforts are beginning to explore the application of extracorporeal shock wave therapy (ESWT) to near lung tissue and transcranial indications. This is driven by a desire to expand the well establish therapeutic and regenerative benefits to a new group of patients. Through mechanotransduction of the incoming pressure pulse, a cascade of biochemical responses is triggered within the...
Human liver tissue models are of great interest for toxicology analysis in drug development and as liver disease models. All solid tissues depend on sufficient oxygen supply for survival and on controllable oxygen tension for their proper function. Liver tissue models pose a particular challenge in oxygenation given the high oxygen consumption rate of hepatocytes and the well documented...
"Angiogenesis, the process by which new blood vessels sprout from existing surrounding ones, is essential for the survival of implanted tissue engineered constructs. In fact, the lack of proper re-vascularization and core necrosis is the main pitfall of many developed biomaterials (1). In this study, we describe a highly tunable hydrogel system for the growth of capillaries based on...
The COVID-19 pandemic has shown how revolutionary treatments based on gene therapeutics has helped overcome a once-in-a-century pandemic and has given new momentum to gene therapy research for a myriad of applications. The field of regenerative medicine is well placed to be a beneficiary whereby, for example, gene therapy might be a valuable tool to avoid the limitations of local delivery of...
"Introduction
Fibrin biomaterial is widely used in the clinic as a tissue sealant and in pre-clinical research as a carrier material for growth factor delivery. In these applications, premature fibrin degradation leads to suboptimal tissue adhesion, recurrent bleeding and limited regenerative efficacy. Therefore, fibrinolytic inhibitors are commonly added into fibrin formulations, such as the...
Impaired wound healing and infections present a major concern for our health systems. Combined with the steady increase of antibiotic resistances and lack of new antibiotic drugs,
there is a pressing need for alternative treatment options, such as antimicrobial light-based therapies. While the germicidal properties of UV light have already been used for a long time, its negative side effects,...
"Immunohistochemistry and immunofluorescence for vascular network analysis play a fundamental role in basic science, translational research, and clinical practice. Due to their versatility and specificity, these techniques are also widely used in the tissue engineering context, where the study of neovasculature is crucial to assess the function of artificial tissue surrogates. However,...
"Introduction: The acquisition of neural signals from the brain cortex has always been of high relevance in the field of neuroscience in order to analyze and interpret brain processes as well as individuate neurological diseases and disorders [1]. Nowadays, the design of a neural interface conformable with the brain tissue is one of the major challenges, since the inadequate conformability...
Age-related macular degeneration (AMD) is a chronic eye disease and the leading cause of irreversible vision loss in millions of elderly people world-wide. The ocular system implicated in this disease is the outer blood-retinal barrier (oBRB) comprised of the retinal pigment epithelium (RPE), the Bruch’s membrane (BrM), and the choriocapillaris (CC). The oBRB plays a pivotal role in...
Growth factor (GF) based therapies in regenerative medicine are limited by the high cost, fast degradation kinetics, and lack of specificity as consequence of the multiple functions of GF in the cell. One common GF therapeutic scenario is the administration of VEGF to support vascularization during tissue regeneration. The therapeutic window for VEGF treatment is narrow: low doses are safe but...
"The development of hydrogels for regenerative medicine has progressed to the point where they are now considered one of the best options for successfully regenerating injured tissues. Their structural similarities to the extracellular matrix (ECM) and their versatility make them excellent candidates to mimic a native environment. Indeed, they are easily chemically modified and can be tuned to...
Background: intrahepatic islet transplantation in patients with T1D is limited by donor availability and lack of engraftment. To overcome these limitations, based on our experience with decellularized rat lung as scaffold for the generation of Vascularized Islet Organ (VIO, lung scaffold repopulated by murine islets and HUVEC cells), we engineered an upgrade based on human blood-derived...
"Introduction: Inducing axial vascularisation of tissue engineering constructs is a well-established method to allow an adequate support of large 3-dimensional tissues. Progenitor cell chemotaxis towards axially vascularized tissues and its role in inducing neo-vascularisation and tissue regeneration has not been well characterized.
Methodology: In a prospective randomized controlled study...
"INTRODUCTION: Iron oxide based magnetic nanomaterial, magnetic nanoparticles (MNPs) and magnetic nanowires (NW) are versatile tools in biology and medicine. MNPs-mediated drug delivery is tested for regenerative medicine (RM) purposes as well as for tumour treatment and diagnostics. Stem cell mediated delivery represents a modality to target remote, metastatic tumors or regenerative sites for...
"Four-dimensional (4D) bioprinting (i.e., fabrication via additive manufacturing of scaffolds characterized by a programmed change, over time, under a predefined stimulus [1]) can be exploited to produce active scaffolds that can modify their shapes upon desired stimulation, thus potentially recapitulating biological processes such as morphogenesis.
In this study, we exploited the 4D...
"Introduction
Gut microbiota is able to communicate with the brain through complex bidirectional routes constituting the so-called microbiota-gut-brain axis (MGBA). Gut microbial dysbiosis increases local inflammation also thanks to the secretion of bacterial lipopolysaccharides (LPS), which disturbs the gastrointestinal and also the blood-brain barrier (BBB) permeability thus propagating...
"INTRODUCTION: When assessing the interaction between nanomaterials and cells, an important step is to image the effects induced by the material to the cell membrane. In order to evaluate the results of the interaction process, scanning electron microscopy (SEM) is typically used. Commonly, an important step during the preparation of biological cell samples for SEM is represented by the...
"Introduction: A major challenge in cartilage tissue engineering (TE) is to develop scaffolds capable of providing an instructive biomimetic environment to effectively drive mesenchymal stromal cells (MSCs) differentiation [1]. Hydrogels have emerged as promising biomaterials for this purpose, due to their biocompatibility and ability to mimic the tissue extracellular matrix [2].
Recently,...
Nanoengineered Mechanically Robust Bioactive Particles Disseminated in Chitosan/Collagen Matrix for Osteoporotic Bone Treatment
Kulwinder Kaur1,*, Ciara Murphy1,2,
1Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
2Advanced Materials and BioEngineering Research (AMBER) Centre, Dublin,...
"Introduction: Neo-angiogenesis describes the development of new blood vessels and takes place during bone healing in the fracture gap. Angiogenesis and the establishment of a functional vascular network is closely associated with bone formation and critical for scar-free healing. Type H vascular endothelial cells (ECs), characterized by high expression of CD31 and endomucin (Emcn) have been...
Introduction:
Recently, tissue engineering still lacks thorough vasculature, which represents a major drawback in developing physiologically relevant tissue constructs. Among others, the design and the biofabrication of blood vessels at the microscale remain challenging, due to their role in nutrient and oxygen exchange, but also waste removal. Parallelly, fiber-based biofabrication...
"Introduction:
The high number of vascular diseases demand for vascular grafts in various clinical application. Nonetheless, a big hurdle for the use of autologous tissue-engineered vascular grafts (TEVG) is represented by the usually long manufacturing time.Therefore, we here present a biohybrid vascular graft and a bioreactor that can provide distinct conditions such as flow, pressure, and...
"Micro- and nanofibrous materials have attracted the interest of the scientific community for the better part of ~30 years, due to their unique properties and potential for applications. Electrospinning is a technique that can produce micro- and nanofibers fast, repeatedly, and with tailored morphology. When fibres are electrospun from biocompatible polymers then they can be used in numerous...
"Introduction
Tissue engineering of human blood vessels is pursued as a clinical revascularization therapy as well as to develop in vitro human blood vessel models with native-vessel like organization. Clinical revascularization strategies that use autologous vessels are hampered by poor quality and limited availability. Synthetic vascular scaffolds may be used as alternative, but for...
"Introduction
Mechanotransduction is a key process in many developmental, physiological and pathological processes in bone. Mechanosensitive ion channels such as Piezo1 and TREK1 are the bonafide mechanotransducers that are critical for various biological processes, plays a critical role in bone regeneration1, 2. We already reported that the Magnetic ion channel activation (MICA) technology...
Myotendinous junction disfunctions due to degenerative musculoskeletal diseases or injuries resulting from strenuous physical activities are still considered an ongoing issue in the field of musculoskeletal tissue engineering. Indeed, the main challenge of biofabrication strategies relies on the development of methods enabling the generation of artificial bio-constructs that can replicate the...
"Introduction
Organ-on-a-chip (OoC) technology shows great potential to accelerate drug discovery and advance personalized medicine. Induced pluripotent stem cells (iPSCs) may enhance the predictivity of the OoC in the assessment of patient’s response to a pharmacological treatment and related toxicities. Nowadays, there are no body-on-a-chip fully based on iPSCs used for drug screening. In...
Introduction. Despite considerable developments in the field of orthopedic implants, complications including poor bone ingrowth and implant-associated infections (IAI) persist. Macrophages have recently been acknowledged to be essential for the implant success in the body, partly through intimate crosstalk with mesenchymal stem cells (MSCs) in the process of new bone formation [1]. However,...
"Introduction: Articular cartilage (AC) defects remain a significant clinical challenge[1]. This is partially due to the challenging nature of recapitulating the complex layered structure observed in the naturally curved AC tissue. While three-dimensional (3D) bioprinting appeared as a promising Tissue Engineering (TE) approach, it has serious limitations in the fabrication of curved...
"INTRODUCTION
Rheumatoid arthritis (RA) is an autoimmune disease that affects diarthrodial joints, characterized by a systemic inflammatory response that leads to progressive joint destruction [1]. Various immune cells are involved, but the exact mechanism of RA development is still unknown, and it is well established that none of the currently available animal models fully represent human RA...
"Introduction
The use of non-covalent self-assembly to construct materials has become a prominent strategy in biomaterial science offering practical routes for the construction of increasingly functional materials for a variety of applications ranging from cell culture and tissue engineering to in-vivo cell and drug delivery.[1] A variety of molecular building blocks can be used for this...
"Bone tissue regeneration (BTR) has been trying to mimic the bone environment in biofabricated platforms. Given the complex bone metabolism, creating a functional, differentiated and biologically compatible platform that stimulates tissue formation in an autonomous way is currently a challenge [1]. Therefore, the development of multifunctional micro-platforms easy to produce and to translate...
"Introduction: Inflammation is a physiological process in healing however, persistent inflammation signals hold deleterious consequences to the tissue and contributes to the inhibition of regeneration. Resolving inflammation remains an unmet challenge with great impact in the management of chronic inflammatory disorders and for the treatment of tissue injuries. Interleukin 4 (IL4) is a...
"Introduction: Endochondral ossification (EO) is the process of bone development via a cartilage template. It involves multiple stages, including chondrogenesis, mineralization and angiogenesis. Importantly, how angiogenesis contributes to EO is not fully understood. To characterise the interaction between human mesenchymal stromal cells(hMSCs)-derived cartilage and blood vessels, we designed...
"Breathing exposes lung cells to continual mechanical stimuli, which is part of the microenvironmental signals directing cellular functions. Therefore, developing in vitro model systems that incorporate physiomimetic mechanical stimuli is urgent to fully understand cell behavior. This study aims to introduce a novel in vitro culture methodology combining mechanical stimuli that simulates in...
"Introduction: Bioprinting is a booming and promising technology to create tissue models, with numerous applications in tissue engineering and regenerative medicine. However, the biomaterials commonly used for bioprinting involve non-physiological stimuli (e.g., sudden changes in temperature, pH, ionic forces) and lack tunability post-printing. These biomaterials are therefore still far from...
"Introduction
Tissue growth in defects is controlled by the local curvature of the substrate and is traditionally regarded to follow the same process of cell organization from large to small defects [1]. At defect dimensions of 100s of µms to a few mms, tissue growth typically follows a centripetal process driven by an inner ring composed of contractile and proliferative cells. In contrast,...
"INTRODUCTION
Islet transplantation is a recognised treatment for type 1 diabetes: islets are transplanted into the liver and the procedure can stabilise blood glucose levels. A major limitation for successful clinical islet transplantation is the significant loss of islets post-transplantation due to an immune mediated inflammatory reaction. Etanercept, a TNF blocker that binds specifically...
"Introduction: The currently available treatments for inflammation often target the symptoms but not the causes, leading to an ineffective management of persistent inflammatory conditions.
Due to the central role of macrophages (Mφ) in the inflammatory response, and overall in healing, innovative strategies to fine-tune the states and functionalities of Mφ may unveil the pathophysiology of...
"Introduction
Prevascularization of tissue-engineered constructs before implantation is used to accelerate anastomosis with the host vasculature and thus to enhance successful implantation. To induce prevascularization, the co-culture of tissue-specific cells with endothelial cells is explored. To date, most co-culture studies are still conducted with human umbilical vein endothelial cells...
"Statement of Purpose: The development of a hydrogel that could be injected and cured in vivo has gained increasing attention. Collagen has been widely investigated as a thermogel in which there are a lot of ionic interaction, hydrophobic interaction, and hydrogen bonding; however, it must be chemically crosslinked also. Diels-Alder cycloaddition occur under mild conditions without the need...
"Introduction: One of the most challenging and daunting task of tissue engineering is the assembly and integration of functional microvasculature systems within the biofabricated tissue equivalents. Having functional vasculature is of the utmost importance to promote the rapid integration of the host’s microvasculature with the engineered one present in the graft, thus enabling an efficient...
"INTRODUCTION: Mesenchymal stromal cells (MSCs) are potential candidates in tissue engineering applications. Nevertheless, MSC-based therapies have fallen short of the initial promise and hype due to the low MSC retention rate caused by the disruption of nutrient and oxygen supplies. Our previous studies established that the lack of glucose (but not oxygen) is fatal to human MSCs (hMSCs)...
"Introduction
Short peptide amphiphiles have been widely reported as building blocks of supramolecular hydrogels for biomedical applications1,2, as they can copycat bioactive protein sequences. However, in the extracellular matrix (ECM), proteins are usually present as glycoproteins with different roles, e.g., storage depots of proteins and co-receptors. In this context, the use of...
Multicellular tissues such as spheroids, organoids can be assembled in vitro from clusters of cells in a spatio-temporal manner, mimicking in vivo physiology and tissue microenvironment, which can leverage pre-clinical evaluation of the efficacy and safety of potential new drugs for diseases such as hereditary, neurodevelopmental, infectious and cancer. In one approach, immortal, primary or...
Despite the success of a handful of companies and the overabundance of research the tissue engineering & regenerative medicine (TE&RM) community has still not delivered the more then 3 decades ago promised health care and commercial break through’s. Yet, rendition of research outcomes into clinical application is still the rallying cry of the modern TE&RM establishment. Deciphering...
"MicroRNAs, short non-coding RNAs, are important regulators of skeletal development. Several individual microRNAs have been shown to alter long bone growth with most interest focused on the cartilage ‘specific’ microRNA, miR-140. We made a new miR-140-null mouse and confirmed the skeletal phenotype, identifying a range of target genes that the microRNA controls. The null mice also have...
Gene therapy is the most promising treatment for recessive dystrophic epidermolysis bullosa (RDEB), however genetic cargo delivery efficiency is still a technical limitation. Viruses are the traditional vector of preference for gene therapy, as virus trophism increase tissue specificity. However, drawbacks related with safety and high manufacturing costs have facilitated the expansion of...
"Introduction
We have derived horse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Pluripotent stem cells undergo unlimited self-renewal and can differentiate into every tissue of the body; properties which can be utilised for therapeutic applications and disease modelling.
We have investigated their application in tendon injuries and catastrophic bone fractures,...
/The abstract will be added later due to patenting/
20967801404
Interest in manned spaceflights has increased in recent years and this brings about a surge in the need for more in-depth research into the adverse effects of spaceflights on the human body. In the absence of gravitational forces there are countless negative effects on the immune system. This dysfunction in the immune system can lead to increased susceptibility of infections by astronauts and...
Three-dimensional (3D) bioprinting has emerged as a class of promising techniques in biomedical research for a wide range of related applications. Specifically, vat-polymerization techniques such as digital light processing (DLP), are highly effective methods of bioprinting, which can be used to produce high-resolution and architecturally sophisticated structures. Nevertheless, conventional...
"3D microenvironment maintains the transcriptome profile of T cells but not B cells in simulated microgravity
The adverse effects of space travel on the human body are abundant and with the rise in interest in manned spaceflight over recent years, there is an increased need for more research into these effects. In the absence of gravitational forces, one of the primary systems to be...
"INTRODUCTION: There remains a substantial unmet clinical need for tissue engineered strategies to heal large volume bone defects. The delivery of microRNAs from biomaterial-based scaffolds presents a promising approach: whereby the scaffold provides a structural support to bone tissue while the microRNAs (miRs) induce the endogenous cells to produce relevant therapeutic proteins and genes at...
Embryos and regenerating systems produce very complex, robust anatomical structures and stop growth and remodeling when those structures are complete. How do cell collectives know what to build and when to stop? Control of this process would provide a radical solution to injury, cancer, and perhaps aging. In this talk, I will discuss new tools and data that are revealing how groups of cells...
Leveraging advances in biomaterials and tissue engineering, it is becoming possible to develop successful reparative, regenerative and tissue modelling solutions. Over more than two decades, we have made progress with studying biodegradable materials for reparative medicine. For example, biodegradable screws and plates were translated to the clinic as osteosynthesis implants. Scaffolds for in...
"Increasing attention is being paid to the use of RNA molecules as agents to facilitate tissue healing. Messenger RNAs (mRNAs) introduced into the cell induce synthesis of their encoded proteins. This approachholds several advantages over traditional DNA-based gene therapy including improved cell internalization and higher transfection efficiencies, without disruption of the host genome. In...
"Studies of cellular differentiation in simulated microgravity reveal an important role for β-actin in mechanosensing
Authors: Oscar Sapkota, Tomas Venit and Piergiorgio Percipalle
Science Division, Biology Program, New York University Abu Dhabi, Abu Dhabi, UAE
Introduction
Mechanotransduction is mediated by the actin cytoskeleton and it is important in helping stem cells determine their...
"Background Synovial membrane-derived mesenchymal progenitor cells (SM-MPCs) are a promising candidate for the cell-based treatment of osteoarthritis (OA) considering their in vitro and in vivo capacity for cartilage repair. However, the OA environment may adversely impact their regenerative capacity. There are no studies for canine (c)SM-MPCs that compare normal to OA SM-MPCs, even though...
"Introduction:
Cystic fibrosis (CF) is a lethal autosomal recessive inherited disease caused by mutations in the CFTR gene encoding the CF transmembrane conductance regulator (CFTR) protein, and has no cure to date. CFTR gene mutations lead to abnormal chloride ion transport in epithelial tissues, which changes the hydration and pH of fluids and mucus, affecting respiratory (main cause of...
"Background Osteoarthritis (OA) is a common degenerative joint disease, that affects the whole joint. Knee joint distraction (KJD) has been proposed as an alternative joint-preserving treatment strategy for relative young patients with end stage OA. Although there is evidence for the clinical and structural benefits of KJD, the regenerative mechanisms behind KJD remain unclear. This study...
"Introduction
Laryngeal cancer is often diagnosed at an advanced stage when treatment options are limited and most often restricted to laryngectomy. As this procedure requires a permanent tracheostoma, it is associated with additional complications such as a high risk of infection, fistulae formation and loss of the natural voice. In addition, restoration of the most important laryngeal...
Background:
Cell adhesion can be guided through the mechanical signals provided by the biomaterials1,2. These signals are transmitted to the cytoskeleton, to the nuclei and finally to the chromatin3. The chromatin remodeling is highly dynamic and sensitive to these cues and imposes extensive effects on DNA-related metabolism, including transcription. Recently, chromatin has been identified as...
"Introduction: Osteoporosis (OP) is characterized by a loss in bone mass and mineral density1. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone formation by increasing the osteogenic potential of mesenchymal stem cells (MSC)2. This pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1) that acts as an antagonist3....
"Introduction:
Intervertebral disc (IVD) degeneration is among the leading cause of low back pain, disability and morbidity worldwide. As the world population ages and only symptomatic treatment exist, IVD regeneration is a major public health challenge for the upcoming years. Human IVD cells are difficult to obtain, especially healthy ones, and murine IVDs present numerous differences with...
Covalent carbohydrate conjugates, referred to as glycans, decorate the surfaces of all mammalian cells and are found on nearly half of all mammalian proteins. Proteins that recognize specific glycan structures, known as lectins, play a central role in decoding the information stored within glycans and converting this information into signals that direct changes in cell behavior. Galectins are...
"Background: Hypospadias is a common congenital abnormality with varying severity. There may be lack of local tissue during hypospadias surgery. Oral mucosa (OM) is widely used for urethroplasties and repair after failed hypospadias in adults. Little is known about the applicability of OM in prepubertal boys because of eventual hormonal effect of puberty on OM. We investigated the androgen...
"It is well known that cartilage possesses a low intrinsic regenerative potential, causing tissue damage that remains unhealed and contributes to a high socioeconomical burden for affected patients. New strategies to restore the properties of load bearing, friction-reducing hyaline cartilage are thus timely. Tissue engineering and regenerative medicine approaches must deal with the high...
"Trauma is the leading global cause of mortality and disability. Patient management after trauma can be challenging, particularly in a multiple trauma setting, a condition characterized by several severe injuries. Multiple trauma can elicit major immunological responses, such as systemic inflammatory response syndrome, which lead to a deterioration in the patient’s condition. The complement...
"The phenotypic characterization of multipotent mesenchymal stromal cells (MSC) still suffers from deficits and the resulting heterogeneity of MSC used in different preclinical and clinical studies hamper the translational success. In search for novel MSC characterization approaches to complement the traditional trilineage differentiation and immunophenotyping assays reliably across species...
"Introduction
Silica based materials have been commonly studied in the field of bone regeneration, due to their bioactivity and osteogenic properties1. However, silica materials have low degradation rates and are brittle, which can be overcome by developing hybrid materials, which include an organic part bound to the silica network2. Despite these can be processed in several shapes, there is...
"Skin ageing is a multifactorial process attributed to both intrinsic and extrinsic factors. Intrinsic ageing is associated with changes that occur with age such as cumulative molecular and cellular damage, while extrinsic ageing exacerbates these changes through the UV exposure. Nowadays, ageing has become an important issue in the world: life expectancy and population have increased, while...
"Regulatory T cells (Tregs) are immuno-suppressive cells which have been recently rediscovered as pro-regenerative cells. When accumulating in injured tissue, Tregs express numerous pro-healing factors such as anti-inflammatory molecules and cytokines. Interestingly, we found that a growth factor (GF) is expressed by Tregs across multiple injured tissues in the mouse. Therefore, we...
Introduction:
Immunomodulation and immunogenicity of mesenchymal stem cells (MSCs) may influence their efficacy and safety, thus being key for their therapeutic use. The immune regulatory mechanisms of MSCs depend mostly on the secretion of different mediators which are not only important for the MSC therapeutic mechanisms but also to facilitate their escape from immune recognition when...
Mesenchymal stem cells (MSCs) have been studied for the treatment of Osteoarthritis (OA), the most common chronic disease of joint cartilage. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, where extracellular vesicles (EVs) may play a major role. It is suggested that MSCs from younger donor sources compete are optimal with...
"Human long-lived plasma cells (LLPCs) are terminally differentiated effector cells of the B-lymphocyte lineage that reside in specialized niches in the human bone marrow (BM) harboring many different microenvironmental niches. LLPCs play an essential role in the humoral immune protection by maintaining constant high-affinity antibody levels against pathogens and their toxic products,...
"INTRODUCTION:
Multiple organs consists of macroporous structures such as the lung, bone, and kidney. However, when creating porous materials, added factors are quickly washed away, thus there is a need to bind them to the material.
Elastin-like Recombinamer (ELR) hydrogel is a type of biomaterial that has proved to have excellent biocompatible properties [2], where we here create a...
"EVs in equine regenerative medicine – challenges and potential therapeutic implications.
Mesenchymal stem/stromal cell (MSC) derived EVs have shown an equivalent therapeutic potential to their donor cells, making them a promising tool for regenerative medicine. However, non-standardised EV isolation methods and the limited availability of cross-reacting markers for most animal species...
Introduction: Three-dimensional bioprinting (3DBP) relies on extrusion-based methods for the printing process, however such methods are known to reduce cell viability due to the introduction of shear forces during extrusion. Additionally, the incorporation of solid elements into bioinks such as ceramic particles that may support bone growth, leads to increased shear forces during 3DBP leading...
INTRODUCTION: Vascular endothelial growth factor (VEGF) is the principal regulator of angiogenesis. Tightly bound gradients to extracellular matrix determine the microvascular endothelial cells fate during organogenesis and tissue regeneration and uncontrolled expression can lead to abnormal vascular growth and vascular tumours 1. Despite advances in tissue engineering, tight spatio-temporal...
Background:
The repair and treatment of large bone defects in patients with compromised bone metabolism due to ageing and medical conditions such as osteoporosis present often a clinical challenge. Therefore adjunctive methods to enhance bone healing are needed. Bone tissue engineering with application of nanotechnology allows to construct biomaterials with desired properties being...
"Introduction
Tendon injuries in humans are a major healthcare concern but they also occur spontaneously in other species including horses. The superficial digital flexor tendon (SDFT) of the horse is a highly relevant model for studying tendinopathies because it is a functional homologue of the Achilles tendon with similarities in aetiopathogenesis and associated risk factors (1,2). Previous...
INTRODUCTION: Within the field of tissue engineering, biomaterial scaffolds augmented with gene therapeutics have emerged as a promising treatment strategy for tissue regeneration. To date, the majority of ‘gene-activated’ scaffolds in tissue engineering have utilised plasmid DNA as the gene therapeutic of choice. Recently, messenger RNA (mRNA) has emerged as an attractive alternative to...
“ActiveLayers” is a platform technology for building medical multilayer films based on layer-by-layer technology. It is characterized by its biocompatibility, environmental friendliness, modularity and multi-functionality where it can be optimized and adjusted to treat several medical problems such as; chronic wounds, non-healing bone fractures, periodontal regeneration and postoperative...
INTRODUCTION: The increased prevalence of obesity over the last few years has intensified the need for physiologically relevant models for the characterization of the mechanisms regulating obesity-linked adipogenic and inflammatory responses. In obesity, there is an unhealthy expansion of adipose tissue, at the expense of hypertrophic processes responsible for the enlargement of adipocytes....
Introduction. In the recent years, three-dimensional (3D) bioprinted hydrogels has been developed and tested for regenerative medicine due to their ability to mimic the anatomical structures [1,2]. Various bioinks that contain polymeric biomaterials, especially natural polymers have been prepared and tested[3] due to their biocompatibility and favorable environment for cell attachment and...
Introduction. Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a five-year relative survival rate (after diagnosis) of only 36%.[1] GBM is characterized for its fast proliferation rate and angiogenic character, making it the leading cause of cancer-related deaths in young adults.[2] During the onset and evolution of GBM, the composition of its...
"Introduction: Tendons are dense connective tissues, necessary for the integrity and function of musculoskeletal system. Poor tendon repair remains a serious clinical problem, due to the difficulties in reorganising the complex multiscale hierarchical structure of native tendons. Tendon stem/progenitor cells (TSPCs) were recently identified as tendon-specific adult stem cells that exhibit...
Introduction
The bone marrow (BM) is a dynamic organ whose main function is to support haematopoietic cells, which assure life-long production of blood. The haematopoietic compartment is supported by the stromal fraction of the BM that comprises mesenchymal stromal cells (MSCs), a heterogeneous cell population that undergoes osteogenic, chondrogenic, adipogenic differentiation. Following a...
3D-Printable biomaterials have potential for fabrication of customized scaffolds for tissue engineering. In the study, methacrylated gelatin (GelMA) and aldehyde-functionalized polyurethane (PU) were synthesized and used to prepare 3D-printable GelMA-PU biomaterials. The GelMA-PU hydrogel and cryogel were optimized for compositions and manufacture processes. The GelMA-PU hydrogel was...
Introduction: The immune system plays a vital role in inducing inflammation, tissue repairing and regeneration. Currently, there is an endeavour to investigate the role of macrophages in bone tissue regeneration. It has been elucidated that macrophages can polarise to proinflammatory M1 and anti-inflammatory M2 phenotypes. However, the role of macrophage phenotypes in bone tissue regeneration...
Introduction: In bone tissue engineering, several attempts have been made to generate artificial bone constructs to replace the autograft and allograft treatment and to enhance bone repair and regeneration. However, engineering bone tissue presents some challenges, mainly based on bone tissue’s gradual variation of several biological, mechanical, and structural features. Another challenge is...
Prostate cancer is one of the most commonly diagnosed cancer in men, and the 5th leading cause of death worldwide1. The lack of the of robust and biologically relevant in vitro model systems that precisely recapitulate the pathophysiology of the human disease delay our understanding of the disease, and thus the discovery of the treatments. Owing the fact that tumor microenvironment plays an...
INTRODUCTION
Pelvic floor dysfunctions (PFDs) are a group of disorders affecting one-third of women worldwide and 50% of women above 55, with pelvic organ prolapse (POP) being the most common. Nowadays, different approaches are used to treat POP, including a surgical approach that consists in the placement of a polymeric mesh. Unfortunately, the employment of meshes has been often associated...
"The field of biofabrication is continually growing due to the increasing life expectancy of humans. The most promising technique in this field is 3D bioprinting, nevertheless, there are still several limitations like low resolution, the challenging printing of hollow tubular structures with low wall thickness due to high shear rates, and low cell alignment. 4D biofabrication is a technique...
Introduction: Advanced strategies in tendon Tissue Engineering might overcome the unsatisfactory results of conventional treatments for tendinopathies [1]. It aims at designing 3D tendon biomimetic scaffolds with adequate physical, mechanical, and biological properties of the native tissue. In this context, 3D tendon biomimetic poly(lactide-co-glycolic) acid (PLGA) scaffolds with highly...
Introduction
This work presents a computational model to study release profile of proteins grafted on scaffolds surfaces. As a case study we investigated the behaviour of ICOS-Fc, a bioactive protein able to rebalance the osteoblasts and osteoclasts activities [1], bound to a polyester blend. Then, a three-dimensional (3D) model was implemented to evaluate the release and diffusion of...
Introduction
Hydrogel fillings have been successful in enhancing artificial conduits for nerve injuries, but the ideal hydrogel is yet to be found. Its discovery is impeded by an overflow of available products as well as a lack of in vitro experiments that fully analyze the effects of these hydrogels on cells crucial for nerve regeneration.
Methodology
This study investigated various...
INTRODUCTION: Type 1 diabetes is an autoimmune condition which through pathological immune system action mediates
β-cell destruction, reducing insulin production capacity1. A proposed replacement for insulin injections and pancreas transplants is the production of semi-artificial pancreas, which combines immunoisolative and oxygen permeable polymer hydrogels with mechanically resistant...
Introduction:
Bioreactors are an important tool to study clinical scenarios under more realistic conditions before heading towards preclinical and clinical studies. We previously showed that, using our standard bioreactor (SB), multiaxial load activates transforming growth factor β1 (TGF-β1), and thereby pushes the mesenchymal stromal cells (MSCs) towards chondrogenesis[1]. Such bioreactors...
Introduction
Tumor models have advanced over the years as scientists have made several improvements. In the past, typically 2D cultures were used. Due to their artificial nature, their results are often not transferable to the human pathophysiology. 3D models are a promising approach for a more in vivo-like microenvironment. Here, the upcoming field of biofabrication makes it possible to...
Introduction
Patient specific, tissue engineered oesophagi represent a possible solution for conditions which currently lack effective therapeutic options, such as long-gap oesophageal atresia1. Histology, the current gold standard for tissue engineering (TE) protocol design, is destructive and 2D, disregarding volumetric information which are essential for confirming the regeneration of the...
Introduction.
Osteoarthritis (OA) is a highly prevalent musculoskeletal disease characterized by a chronic inflammation and joint disability. OA is characterized by cartilage degradation and bone overgrowth. Current pharmacological approaches have a merely symptomatic effect and do not delay disease progression.
Several studies have pointed out that chondrocyte senesce contribute to the...
The biomedical sector is experiencing a technological transformation in its attempt to solve current and next future global health issues. The scarcity of organ donors in a growing elderly population accentuates the need to generate new strategies based on the use of cutting-edge technologies for regenerative medicine.
In recent years, the emergence of 3D bioprinting has allowed great...
Introduction:
Human pluripotent stem cells (hPSCs) are an alternative model for recapitulating key milestones of human embryogenesis during tissue development, which is an important and highly regulated process, yet poorly understood1. Currently, creating an in vitro model that provides the appropriate microenvironmental cues in a spatiotemporal manner to enable hPSCs to differentiate into...
Introduction
Autologous bone transplantation is the gold standard for reconstruction of large bone defects in the fields of orthopedics and odontology. However, limitations such as the grafting mass needed, its availability, and donor site morbidity has led to the search for osteo-inductive biomaterials that possess similar composition and structure to the main inorganic component of bone...
Stress urinary incontinence is the most common type of urinary incontinence. Actual standard therapeutic modalitie offer symptomatic relief without treating the underlying disorder. Therefore, we developed a novel technology to apply cells for recovery of the urethral sphincter by waterjet (WJ). Based on our previous study in cadaveric samples1, we investigated if a) porcine muscle−derived...
Introduction. Market estimates show that the bone replacement market is estimated to reach USD4.94 billion by 2030, within the orthopaedic, oral and maxillofacial reconstructive sectors. Statistics provided by National Center for Biotechnology Information, estimated that in 2015 around 7 million people underwent bone replacement procedures in America. According to the World Health...
TITLE: A study on hBM-MSCs chondrogenic commitment by 3D Collagen scaffold loaded with PLGA nanocarriers for TGF-β1 controlled release
AUTHORS: Lamparelli Erwin P.1, Lovecchio J.2, Giordano E.2, Maffulli N.1, Della Porta G. 1,3(*),
1 Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, Baronissi (SA), Italy
2 Department of Electrical, Electronic and...
The combination of 3D bioprinting and tailored bioreactor designs allows the fabrication of advanced in 3D in vitro models. However, there is a lack of biomimic vessel models focusing on chemotaxis, which enable the investigation of the effect of simultaneous external stimuli. In this study, we propose a novel bioreactor system combined with bioprinted microvessels embedded in fibrin-based...
"Introduction:
Ovarian Cancer (OC) research is limited by the lack of an appropriate in vitro model of the tumor microenvironment. We utilized a perfusion bioreactor, suitable for the culture of up to 40 cell-seeded scaffolds (1), at velocities mimicking the cellular conditions in the extracellular fluid flow (2), to construct a new OC model. Our hypothesis was that operating the reactor at...
Introduction
Bone metastases are the most common cause of cancer-related pain and often lead to complication such as bone fractures and spinal cord injury, all of which can severely erode patient’s quality of life. Even tumors such as breast cancer that can be now early diagnosed, leading to a positive resolution, may present increased morbidity and mortality if they metastasize to bone. The...
INTRODUCTION: Many human disorders display unknown tissues relationships affecting disease progression and drugs response (1). While in vitro assays fail in recapitulating organ-organ connection, animal models reveal species-specific drug outcomes. To this purpose, a novel multi-organ microphysiological system (MIVO®) has been adopted to fluidically connect 3D ovarian cancer tissues with a...
"Introduction
An osteochondral scaffold with a superficial collagen layer for cartilage replacement and a collagen/Magnesium-hydroxyapatite (Mg-HA) layer for bone replacement has demonstrated good clinical results in osteochondral defects [1]. However, subchondral bone repair remained suboptimal, with a long maturation time. In this study, we first confirmed the role of Mg-HA into the...
"Introduction
Most of the efforts in creating vascular structures using 3D printing have been concentrated on extrusion type of printing. However, mimicking vascular structures such as arterioles (100 µm diameter) is difficult due to the limitations in resolution that extrusion printing has. Inkjet 3D printing is a droplet-based type of printing that has resolution of 30 µm which can achieve...
"Introduction
Bioresorbable stents (BRS) are designed to provide a temporary support to the vessel wall while the structure slowly degrades until completely resorbed. In order to prevent neointimal hyperplasia, antiproliferative drugs such as everolimus are loaded into stents, although endothelialization may be delayed due to long release periods [1]. Additive manufacturing (AM) and...
Introduction:
Critical-sized bone defects can result from trauma, inflammation, and tumor resection. Such bone defects, often have irregular shapes, resulting in the need for new technologies to produce suitable implants. Bioprinting is an additive manufacturing method to create complex and individualized bone constructs, which can already include vital cells.
In this study, we present...
Urethral fibrosis affects 1 out of 1000 individuals within their lifetime, most of those affected being male. It shares the hallmarks of other types of fibrosis (e.g., liver or heart), namely, the activation of myofibroblasts, overabundance of collagen and the spread of scarring from the initial focus to the surrounding tissue, leading to organ failure. It can be caused by trauma, infection...
Introduction
The development of reliable preclinical systems for anticancer drug testing has become an imperative considering that over 96% of oncology drugs that reach clinical trials ultimately fail [1]. Traditional cancer models comprising monolayer cell cultures (2D) where the cells adhere to the flat surface of a culture flask cannot recapitulate the complex 3D structure of in vivo...
Introduction
In recent years of regenerative medicine research, polymers have been utilized in an enormous number of types, variations and modifications, yet their potential is far from exhausted. One of the polymers with great variability of shapes and properties is polyurethane. It is a relatively cytocompatible polymer spinnable into nanofibers, allowing the natural extracellular matrix to...
Introduction
Around 10% of long bone fractures display inadequate bone regeneration, leading to delayed- or non-unions. Amino acids have shown to play important roles in bone regeneration. In particular, citrulline has revealed itself as an enhancer of bone regeneration in murine bone defect healing models. Oral citrulline supplementation stimulated callus formation and lead to a balanced...
Introduction
Cycles of vascular growth and regression can be observed in physiology as well as pathology. Angiogenic phases are intermitted by vessel regression in the menstrual or hair cycle and tumor-supplying vasculature can regrow after therapeutic intervention through anti-angiogenic therapies (AATs)(1-3). While AATs based on limiting the availability of VEGF have been successfully used...
Introduction
In recent years, there has been growing evidence that mesenchymal stem cells (MSCs) are not truly immune-privileged but immune-evasive, and thus, their recognition and elimination by the immune system in the allogeneic setting should be considered. In this regard, antibody production after MSC allogeneic administration MSCs has been demonstrated in several species, including...
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and intra-articular cell infiltration. Currently, RA is still incurable, and treatment is aimed at relieving symptoms. Therefore, RA patients must be taken drugs continuously. Methotrexate (MTX) has been used for the treatment of RA since the 1980s and is the most used drug among disease-modifying...
"For achieving early intervention treatment to help patients to delay or avoid joint replacement surgery, a personalized scaffold should be designed coupling the effects of mechanical, fluid mechanical, chemical and biological factors on tissue regeneration, which results in time-consuming and cost-consuming trial-and-error analyses to investigate in vivo test and related experimental...
The recent emergence of nanotechnology has provided a new therapeutic modality in case of silver nanoparticles. Dressings containing silver form the basis for the treatment of burns and wounds, either acute or chronic ones. The aim of the study was to examine silver release from the different wound dressings: commercially available (Atrauman Ag, Aquacel Ag) and experimental (FKDP-AgNPs) using...
"Introduction: In recent years new therapies, such as skin cell lines injection and bioengineered autologous skin substitutes (BASS) technology, have emerged to promote re-epithelialization of damaged areas such as cutaneous wounds and ulcers or to treat patients with severe burns. Antiseptics are commonly used during wound healing to avoid serious infections, but some of them could have the...
Harnessing advancements in biodegradable polymers has made tissue engineering an increasingly viable alternative, offering the benefits of established approaches whilst minimising their drawbacks. Whilst the choice of material, indication for use and ideal reconstruction are for debate, a reproducible method of assessment is required to allow for optimisation of pre-clinical technology as well...
A novel decellularized bone matrix was established by the supercritical carbon dioxide (SCCO2) extraction technology. The most commonly employed surgical technique is bone grafting, to enhance bone regeneration in orthopaedic surgery. The current study investigated the role of SCCO2 -decellularized bone matrix (scDBM) as bio-scaffold seeded with allogeneic adipose-derived mesenchymal stem...
"Liver disease is a major healthcare challenge, accounting for around 2 million deaths yearly worldwide. Although liver transplantation is the best way to re-establish normal liver function, less than 10% of transplantation needs are currently met. The EU Horizon 2020 OrganTrans consortium aims to address this issue by developing a liver tissue printing platform for transplantation. In this...
"Introduction: Over the last decade, an increasing relevance has been given to the use of semi-quantitative and quantitative methods to evaluate histological and immunohistochemical images through image analysis software. Most of this software only require image input. However, the usability of classic image processing, including classic segmentation algorithms, is limited. Machine learning...
"INTRODUCTION
Vascularization remains a critical factor for the success of various applications in the biomedical field. Insufficient blood vessel systems often limit the availability of replacement tissues via TERM.[1] Hence, there is a great interest in materials that potentially improve vascularization. The mechanical properties of hydrogels strongly influence cell behavior and...
Introduction: Cancer is increasingly a global health issue. Each year, millions of people are diagnosed with cancer around the world and it is still a leading cause of death. Despite the significant improvement in treatment and prevention, there is a critical need for more effective strategies, like the use of synthetic or natural agents to inhibit, retard, or reverse the process of...
Introduction:Hydrogels are biomaterials that possess appropriate physicochemical and mechanical properties enabling the formation of a three-dimensional, stable structure used in tissue engineering, providing an environment conducive to the survival and proliferation of cells. The cytotoxicity test is performed to assess the overall toxicity of developed materials. Evaluation of the...
Introduction
In advanced prostate cancer (PCa), cancer cells preferentially metastasise to bone. At this stage, survival rates drop from 56% to 3%1 and most treatment options for patients remain palliative. The bone metastatic niche (BMN) is indeed a complex microenvironment with various cell populations that have different roles in cancer cell migration, survival, and therapy resistance2....
INTRODUCTION
Ameloblastoma (AM) is a benign, epithelial tumour of the jawbones originating from the residual epithelium of the tooth germ. AM shows a locally aggressive behaviour characterised by progressive bone resorption. The precise molecular mechanisms behind the disruption of bone homeostasis are unclear. We developed a novel 3D model composed of an AM tumour mass and a bone stroma to...
Globally, approximately thirty-one percent of worldwide deaths are caused by cardiovascular diseases (CVD). Most CVDs are usually a late-stage clinical manifestation of atherosclerosis, which has been shown to be dependent on the complex interactions between various physical and biological factors of a blood vessel in a patient-specific manner. These factors include the anatomy of the...
*Purpose: Tissue engineering is an interdisciplinary field involving activities based on two interrelated areas: developing new methods to repair, regenerate and replace damaged tissues and organs. Currently, the most suitable materials for bioprinting of living constructs are biomaterials based on decellularized extracellular matrix (ECM). In this researches, we made two independent...
Microvasculature is essential for the exchange of gas and nutrient for most tissues in our body. Some tissue structures such as the meniscus presents spatially confined blood vessels adjacent to non-vascularized regions. In biofabrication, mimicking the spatial distribution of such vascular components is paramount, as capillary ingrowth into non-vascularized tissues can lead to tissue matrix...
Stem cells, especially human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells, are attractive sources of cells for regenerative medicine and have been used in clinical trials. One of the difficulties of applying human pluripotent stem cells (hPS cells, including hES and hiPS cells) in the clinic is that hPS cells cannot be cultured on conventional tissue culture...
"Biological organisms have been a source of inspiration for the development of high-performance materials. Particularly, the optimized physical adhesion between pollen grains and bees’ leg hair during the pollination process, where pollen grains diameter matches the distance between the bees' hair, has encouraged the development of an optimized biomimetic drug dressing. After satisfactory...
"Introduction: The burden of central nervous system (CNS) diseases continues to increase especially with an aging global population. The interface between the brain and the blood is governed by the specialized endothelium which composes the blood-brain barrier (BBB). Brain metastasis has a high rate of incidence from melanoma, breast and lung cancers and the BBB is strongly involved in these...
Introduction: Pelvic organ prolapse (POP) is a condition in which defects of supportive tissues due to changes in collagen metabolism result in bladder, bowel, and uterus descending into the vagina, which results in a lifetime surgery risk of 10% worldwide [1]. Surgery comprises the plication of healthy connective tissue to cover the defect, which is called native tissue repair (NTR). However,...
"Purpose: Tissue engineering is currently on advanced stage of development which gives a possibilities for novel strategy of personal treatment of type 1 diabetes. AIM: In the following study, a bioink based on ECM derived from decellularization of porcine pancreas was applied for 3D bioprinting.
Methods: The SCID (n=60) and BALB (n=20) mice were used as a model for in vivo study. Porcine...
There is lack organs for transplantation. The transplantation of the pancreas is recommended in diabetes with complications. The combination of cell biology and 3D-bioprinting can create organs with vasculature which should be functional. There are some issues to be solved: leakage, thrombosis, enhancement against high pressure, connecting organ to the recipient. The purpose of this study was...
"Patterning and manipulation techniques have been used to fabricate 3D cell cultures in tissue engineering. The contactless magnetic manipulation approach is a rapid, simple, and cost-effective method that requires paramagnetic agents [1-3] or magnetic materials [4]. Here, to obtain patterned 3D cellular structures a new alginate-based bio-ink formulation was developed to fabricate 3D cellular...
"Introduction. Intervertebral disc (IVD) degeneration is one of the main cause of low back pain (LBP), affecting over 600 million individuals worldwide. Mechanisms associated with the degeneration remain poorly characterized, in part due to the lack of adequate IVD models. Reproducing in vitro the complex structure of an IVD, with its gelatinous core Nucleus Pulposus (NP) surrounded by the...
Urochordates are the closest invertebrate relative to humans and commonly referred to as tunicates, a name ascribed to their leathery outer “tunic”. The tunic is the outer covering of the organism which functions as the exoskeleton and is rich in carbohydrates and proteins. Invasive or fouling tunicates pose a great threat to the indigenous marine ecosystem and governments spend several...
"Biotechnology engineering in a microgravity environment receives much attention these days. The absence of sedimentation enables scientists to combine any number of substances in an even mixture, prevent cell sedimentation, and enhance agglomeration into a natural 3D formation. Additional beneficial is the absence of hydrostatic pressure, permitting secondary forces like diffusion and surface...
Introduction
Stem cell-based therapies are considered one of the most promising disciplines in the field
of biomedicine. Bladder cancer patients could benefit from such therapies directed to promote healing after invasive surgeries or to lessen urinary incontinence, a common side effect of both cancer itself and the treatment. One particularly attractive source of cells for bladder...
Introduction: Bioactive factors contained in Platelet Lysate (PL) promote the isolation and proliferation of Mesenchymal Stem Cells (MSCs) and the growth of cell lines. It is well known that PL not only enhances cell proliferation compared to Fetal Bovine Serum (FBS) without affecting the cell differentiation capability, but it is also able to activate resting quiescent cells to re-enter cell...
Introduction
Regeneration of cartilage tissue is a difficult and lengthy process. An active fibrous substrate that mimics the random arrangement of fibres in the extracellular matrix (ECM) may be a promising strategy to aid the self-repair process. Fibrils form interconnected, three-dimensional network whose morphology promotes oxygen and nutrient delivery to cells. Tuning the surface...
INTRODUCTION: Hypertrophic chondrocytes mediate the enduring pathway for endochondral bone formation. However, challenges in tissue-engineered bone constructs include functionality under the mechanical environment inside in vivo conditions. We aim to fabricate a mechanically stable Silk fibroin (SF) carrier incorporating decellularized cartilage derived extracellular matrix (CD-ECM) and...
"INTRODUCTION: Osteoarthritis (OA) is the most common arthropathy and a leading cause of pain and disabilities worldwide. Globally, OA affected more than 300 million people; however, despite its prevalence and importance, even economically, the comprehension of its molecular background is limited. Moreover, as OA is characterized by a complex molecular network, it is unlikely that targeting a...
In the past few years, mesenchymal stromal cells (MSC) have been identified as a potential therapy to inflammatory diseases due to their ability to secrete immuno-modulatory and anti-inflammatory factors. Considering the risk of cell leakage outside the target site and the poor survival rate after a local injection, for example in the joint, cell encapsulation in hydrogels could overcome these...
While both, regenerative medicine and tissue engineering shift from 2D based models towards 3D models, problems related to imaging of those difficult constructs became more relevant than ever. One of the most attractive technics used by the aforementioned fields is 3D bioprinting based on hydrogel scaffolds. Unfortunately, due to the complexity of the growth kinetic of cells in the printed...
"Introduction: High IL-1β levels are often found in osteoarthritic (OA) joints. Moreover, IL-1β credibly induces post-traumatic OA. Since cell morphology is an important regulator of cell behavior, we investigated how acute vs. chronic IL-1β dynamically changes multifaceted aspects of cell morphology in healthy and OA chondrocytes in relation to phenotypic outcome.
Methods: Acute inflammation...
Introduction
Human tissues are structurally and compositionally heterogeneous, often consisting of gradients in architecture, extracellular matrix constituents, cell phenotypes, and biochemical factors. Mimicking the structural complexity through scaffold designs for in-vitro tissue regeneration is challenging and yet to be achieved. Melt Electrowriting (MEW) is a high-resolution additive...
Introduction
The overall burden of osteoarthritis (OA) in the US is estimated at $136.8B annually, an amount that surpasses that of tobacco-related health effects, cancer, and diabetes. Current interventions are not effective in arresting the progressive cartilage degeneration. Stem cell therapy is the new frontier for OA treatment. Intra-articular injection of mesenchymal stem cells (MSCs)...
CERIUM, ZIRCONIUM AND COPPER DOPED ZINC OXIDE NANOPARTICLES FOR BONE REGENERATION AND ANGIOGENESIS
H Akhtar1, J A Darr2, T Ashton2 , AA Chaudhry3, and I U Rehman4 & GC Reilly1
hakhtar2@sheffield.ac.uk, j.a.darr@ucl.ac.uk, t.ashton@ucl.ac.uk, aqifanwar@cuilahore.edu.pk, i.u.rehman@lancaster.ac.uk, g.reilly@sheffield.ac.uk.
1 INSIGNEO institute for in silico Medicine, University of...
"The biofabrication of living constructs containing hollow channels is critical for manufacturing thick tissues. Current technologies are limited in their effectiveness in the fabrication of channels with diameters smaller than dozens of micrometers.
Here we present advances in continuous chaotic bioprinting, an additive manufacturing technique that enables the creation of complex biological...
Characterisation of Collagen/Chondroitin Sulfate and Collagen/Hyaluronic Acid Scaffolds to Model the Prostate Cancer Microenvironment.
Nezar Kamal1,, Aamir Hameed1, Ciara Murphy1,2,3, Caroline Curtin1,2,3
1Tissue Engineering Research Group (TERG), Department of Anatomy & Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland. 2Trinity Centre for...
Introduction: The studies of MSCs therapeutic action have been conducted over the past 20 years for a variety of human pathologies, both in model experiments in animals and in clinical trials. However, there are very few studies on the effects of MSCs in viral infections. Thus the present work aimed to study the effects of MSCs administration at the very beginning of the acute phase on the...
This study developed novel stimuli responsive injectable hydrogels composed of a biocompatible and anti-adhesive cartilage acellularized matrix (CAM) and a diselenide bridge-containing cross-linker by using norbornene (Nb)-tetrazine (Tz) click chemistry. The crosslinking reaction between CAM-Nb and the Tz-cross-linker evolved nitrogen gas and resulted in injectable hydrogels with highly porous...
Introduction
Despite increased global incidence of kidney disease, their mechanisms are yet not fully understood. Among the different segments of the nephron, the functional unit of kidneys, the proximal tubule (PT) is most susceptible for toxicant-induced injury because of its role in xenobiotic secretion and reabsorption. Moreover, genetic defects in transporters may lead to metabolic...
Introduction: The main aim of tissue engineering is to design biological substitutes in order to enhance and restore damaged tissues or organs, and biomaterials for fabricating the scaffolds play a crucial role. Collagen (COL), the main part of the ECM and a group of structural proteins which contributes to the extracellular scaffolding, was considered for scaffolds preparation. Studies have...
This work is based on the functional coupling of integrins, boron (B) transporter (NaBC1), and growth factor receptors (GFR) after their activation. In our previous work, we have demonstrated that active-NaBC1, co-localise with fibronectin-binding integrins (α5β1/αvβ3) and GFR producing a functional cluster that synergistically enhances biochemical signals and crosstalk mechanisms,...
INTRODUCTION: One of the main causes of stroke in acute cerebrovascular accident is ischemia, which begins with the formation of acute neuronal energy deficiency with subsequent activation of "ischemic cascade" reactions, which leads to irreversible damage in nerve tissue. But the restoration of perfusion of ischemic tissue contributes to the deepening of metabolic disorders in the brain,...
Treating immune-related diseases, which incidence is steadily growing, is still a challenge. Among the new treatments under development, mesenchymal stromal cell (MSC) transplants seem to be one of the most promising. Although MSC-based therapies are being implemented into the clinic, many aspects regarding these procedures requires further optimization. A new trend in translational medicine...
Introduction: The term “extracellular vesicle” (EV) is broadly used to describe naturally released cellular vesicles with a lipid bilayer and without a nucleus. EV represent a heterogeneous population that is generally categorized into subpopulations based on characteristics such as size, biogenesis, function, and composition. The field of extracellular vesicle (EV) research is growing...
Introduction
First place of interaction between the biological and artificial system is the surface. Surface properties can influence many cellular functions. The efficient way of surface functionalization is thin composite films prepared in situ in colloidal dispersion mode. The combination of intrinsic electrical conductivity with easy preparation and modification procedures of polyaniline...
"Introduction
The medical device sector relies on the detail-oriented and often cutting-edge research of fundamental scientists. This type of research requires public funding to survive. As such, engaging effectively and meaningfully with the public in the research undertaken, for people to understand and appreciate the importance of funding lab-based, discovery research is vital for...
"Introduction: In the last decade many advancements have been made in engineering tissues that function as replacement for malfunctioning or damaged tissues and organs(1–3). However, current methods are limited to either thin tissues such as skin and bladder(4), or small sized tissues used in small rodent models(2). Scaling these tissues up towards clinical relevant sizes currently remains a...
Introduction:
Most current animal vaccine regimes involve a primary vaccination followed sometime later by a booster vaccination. This presents challenges when vaccinating difficult to access animals such as livestock. Mustering livestock to deliver a vaccine boost is costly and stressful for animals. Thus, we have produced a platform system that can be administered at the same time as the...
"CONTROLLING CELL RESPONSES WITH SURFACE POTENTIAL ON ELECTROSPUN POLY(L-LACTIDE) (PLLA) SCAFFOLDS PRODUCED WITH POSITIVE AND NEGATIVE VOLTAGE POLARITY
Martyna Polak1*, Urszula Stachewicz1
1Faculty of Metals Engineering and Industrial Computer Science, AGH University of Science and Technology, Poland
*mpolak@agh.edu.pl
Abstract
Cell responses are essential for all tissue...
Introduction
Melt electrowriting (MEW) is an additive manufacturing (AM) technology that accurately fabricates polymer fibres onto a collector. The characteristic feature of the technology is a strong electric field between the nozzle and the collector that allows to achieve microscale resolution of the fibre, from 0.8 to 50 microns[1]. With the nozzle raised above the collector, the material...
Introduction
Craniofacial bone defects can be caused from birth defect anomalies and road traffic accidents and affect vital functions such as chewing, swallowing, speaking, and breathing1. Autografts are the current gold standard for treating these defects but suffer from limited tissue available for harvest, long operation times, and donor site morbidity. Tissue-engineering has been known...
"Research concerning 3D constructs of biological tissues has made enormous progress over the past twenty years. The ultimate aim is to create in vitro models that mimic, at least in part, morphology and function of biological tissues, leading to future applications ranging from clinical modeling to clinical transplants.
Despite the progress in obtaining various types of constructs (organoids...
The research of extracellular vesicles (EVs) has boomed in the last decade, with the promise of them functioning as target-directed drug delivery vehicles, able to modulate proliferation, migration, differentiation, and other properties of the recipient cell that are vital for health of the host organism. To enhance the ability of their targeted delivery, we employed an intrinsically...
Introduction
Osteoarthritis (OA) of articular cartilage is a progressive and debilitating disease, often necessitating a total joint replacement. Between 2005 and 2015 the worldwide prevalence of OA increased by 32.9 % (from 17.9 to 23.7 million cases) [1]. There is therefore a demand for early stage interventions to stave off or delay replacement surgery. A potential treatment is a...
Pancreatic islet transplantation is a promising therapeutic advancement in the treatment of type 1 diabetes; however, a major obstacle remains in supporting cell function post-transplant. To identify possible extracellular matrix (ECM) proteins for the functionalization of islet encapsulation devices, we investigated the presence of ECM in native pancreatic tissues and in our EndoC-βH3...
Development of degradable blood contacting devices (BCDs) is often associated not only with weak mechanical properties and high molecular weight of the degradation products, but also with long-term thrombogenicity issues. Poly(2-hydroxyethyl methacrylate) (pHEMA) emerges as a promising hydrogel to be used in BCDs mainly due to its bio/hemocompatibility and non-fouling character. However,...
Introduction
In addition to the osseointegration of the implant’s surface, a sufficient adhesion of the abutment's surface to the soft tissue is a crucial factor for the longevity of the implant. The soft tissue seal surrounding natural teeth acts as a barrier against deleterious stimuli in the oral cavity, thus preventing bacteria penetration and protecting the underlying alveolar bone....
Introduction: Age-related macula degeneration (AMD) is a blinding neurodegenerative disease of the retina. It affects 4% of the population over 60. For over 90% of patients there is no cure due to cellular atrophy of the retina. Progressive deposit accumulation (drusen) under the retinal pigment epithelium (RPE) is the hallmark of the disease. Currently, no single (in vitro) model...
"Introduction: The extracellular matrix (ECM) is a highly organize structure that represents the major structural component of the tumor microenvironment. The ECM is a non-cellular network of proteins that provide to the tumor cells the capability to invade, proliferate and migrate. Indeed, the tumor microenvironment represents a dynamic scaffold, and the study of the ECM structure represents...
Electrospun fiber comprising bioactive substrates has potential to implant into the wound site as a reliable therapeutic approach in tissue regeneration. Here, electrospun polyvinyl alcohol conjugated tyramine (PVA-Tyr) and collagen (Col) fibrous mat containing chitosan nanoparticle loaded with epigallocatechin 3-gallate (NCs-EGCG) developed and the composite was applied to evaluate in vivo...
"Introduction: Soft tissue-engineered constructs (sTECs) require tailored dynamic changes in their structure-properties-process (SPP) relations to preserve their functionality throughout the tissue regenerative process. At the initial stages of regeneration, a highly interconnected architecture is recommended to accelerate plaque adhesion and blood clot formation. At later stages of...
As a valuable resource for cell therapy, spermatogonial stem cells (SSCs) have raised hopes for the treatment of male infertility. Various 3D methods have been developed to produce cellular aggregates and mimic the organization and function of the testis. In order to improve in vitro spermatogenesis, the present study was performed with the aim of forming testicular organoid (TO) from mouse...
Tissue engineering has shown and still shows the potential to improve quality of life, especially in the cell therapy industry. An area of interest is in the in vitro production of red blood cells (RBCs). Blood transfusion is one of the most widespread forms of cell-based therapy and has been in use for over 50 years. However, the World Health Organisation (WHO) aims for each country to have...
Introduction: Cleft palate is a congenital condition affecting the development of maxillofacial bones. Current treatment is based on the surgical repair of the soft tissues in order to generate a physical barrier between the oral and nasal cavities. However, this treatment is associated with subsequent bone hypoplasia and misdevelopment in most patients. In this regard, we recently generated a...
An Osteochondral defect (OCD) refers to an area of local damage in the articular cartilage and in the underlying subchondral bone (SB). Trauma related to an injury, or a long-term chronic disease are the main causes of this defect. Tissue engineering osteochondral scaffolds (OCSs) is a method used for the treatment of OCD. This method could achieve the regeneration of the damaged tissue using...
"Recent works on dynamic hydrogels, using non-covalent and/or dynamic covalent linkages, have shown that dynamic and spatial-temporal complex materials are promising step-towards the recapitulation of extracellular matrix (ECM) functionality and structure 1-5. However, the uncontrollable network properties across timescales make these dynamic hydrogels insufficient for fully recapitulating the...
INTRODUCTION
Biophysical parameters are integral to various pathophysiologies, such as fibrosis and cancer. Systematic investigations of such parameters and how they influence cell behaviour and disease progression are feasible in 3D in vitro models of disease.
In this project we used collagen I, the most abundant extracellular matrix protein, to engineer 3D constructs, both as soft...
Introduction: Fibroblast populated collagen matrices (FPCMs) are well established as a model for assessing the behaviour of fibroblasts. When used on a fixed substrate, FPCMs have also proven to be a reliable model for the study of tissue healing. Until now, such techniques have only been used with dermal fibroblasts to examine skin healing. Our work will develop a fixed (tethered) FPCM seeded...
"Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide1. According to molecular signatures, it can be classified into four Consensus Molecular Subtypes (CMS) with CMS4 tumours being associated with worst relapse-free and overall survival2. CMS4 tumours are rich in mesenchymal stromal cells (MSCs) and have increased angiogenesis and inflamed immune phenotype....
Biomedical research is in need of evolving towards more sustainable models by adopting the concept of the three Rs (reduction, refinement, replacement of animals in research). Additionally, economic limitations in developing countries should also be taken into consideration. This project aims to develop a non-animal sourced and low-cost biomaterial that can be used to create accurate tissue...
Introduction: Since the cardiac tissue possesses limited regenerative capacity, cardiovascular diseases still remain one of the most common causes of death worldwide and their currently existing treatment approaches, including cell-based therapies, are still unsatisfactory. Thus, new therapeutic strategies need to be developed, which is a one of the challenges of modern biomedical sciences....
Tissue engineering has undergone a great revolution in terms of the strategies, technologies and materials it uses (1). In this way, much more complex approximations have been proposed achieving a notorious improvement of the treatment of injuries as frequent as tendinopathies. In this sense, 3D bioprinting could help for the development of scaffolds whose biological or mechanical...
Introduction
A major drawback of most chemo- and radiotherapeutic cancer treatments is their toxicity to the ovaries, meaning they may affect fertility and/or endocrine function of female patients. The state-of-the-art method nowadays is the cryopreservation of the ovaries. However, with transplantation of ovarian tissue after the end of cancer treatment there is always the risk to also...
The injured spinal cord (SC) generates a unique and complex pathophysiology which presents a multifaceted challenge for repair. Broadly, normally supportive astroglia become reactive following injury and form a glial scar. This scar in turn inhibits recovery by releasing an impenetrable inhibitive extracellular matrix (ECM), which prevents axonal regrowth. Tissue engineering approaches aim to...
Introduction:
Breast cancer is the most frequent cancer among women. New therapeutic approaches need to be introduced to develop an effective cancer therapy, which could inhibit, or reverse cancer spread to distant locations. The most prevalent cancer treatment method is resection, during which the tumor with the adjacent tissue (margin) is removed. In such case, patient-tailored hydrogel...
Curcumin is a well-known natural anti-inflammatory agent derived from turmeric, and it is commonly used as an herbal food supplement. Nowadays, the use of curcumin has also reached the biomedical and tissue engineering fields. To overcome the hydrophobicity of curcumin, nanoparticles (NPs) were synthesised using a solvent evaporation, oil-in-water emulsion method. The curcumin nanoparticles...
Introduction: Urinary bladder regeneration using tissue engineering is one of the major challenges of reconstructive urology. Commonly used urinary bladder reconstruction techniques that utilize gastrointestinal tissues, are associated with many complications. One of the most promising alternative seems to be the use of bladder acellular matrix (BAM). The use of BAM in clinical practice...
Introduction: Hydrogels are promising biomaterials for regenerative medicine due to their flexible shape, resemblance with the extracellular matrix and capacity to deliver and release bioactive compounds. Especially, injectable hydrogels gained popularity due to their minimal invasive application [1]. Fucoidan is a sulfated polysaccharide from the cell wall of brown algae with multiple...
Introduction:
Cells and tissues are an essential part of many medicinal experiments – either as main players in novel therapies or as a waste material accompanying medicinal intervention (or both). Regardless of their role in therapy they can be collected and stored by biobanks. We present the example of a very effective pathway from a clinical trial of Advanced Therapy Investigational...
Introduction
Cartilage structures can be damaged causing two types of injuries: focal; the lesion is restricted to a concrete zone or diffuse; the lesion affects a broad area of the articular cartilage. This type of lesions appears due to the reduced self-healing capacity of articular cartilage. Diffuse damage is much more difficult to treat. As the damage progresses up to the point where the...
"Introduction
Tympanic membrane perforations (TMP) represent a common cause of visit to the ENT clinic, usually due to recurrent infections or trauma. The rate of recovery for each perforation depends mainly on the size of the perforation and the secondary infections developed. Although most TMPs heal spontaneously, some patients can develop a chronic defect. The traditional technique used in...
There is still need for development of biomimetic hydrogels capable to recapitulate the native environment of bone tissue, as those used currently lack of tissue-specific composition and yield suboptimal tissue formation. Decellularized extracellular matrix (dECM) is composed of tissue-specific biopolymers and growth factors. Moreover, it undergoes gelation at physiological temperatures....
INTRODUCTION
Cancers are one of the leading causes of death worldwide. Failure to obtain effective treatment could be attributed to the irrelevancy of commonly utilized two-dimensional (2D) in vitro and animal models in drug evaluation. Three-dimensional (3D) in vitro models aim to provide more resemblance to in vivo cancer cell microenvironment and therefore represent promising tools for...
In this study, we utilized the decellularized extracellular matrix (ECM) under the ultrasonication to obtain the ultrasonic decellularized ECM (UdECM). In SDS-PAGE studies, the results demonstrated that UdECM was mainly composed of type I collagen. The mechanical strength increased with the increase of concentration of UdECM in rheology studies. In addition, the scanning electron microscope...
Introduction:
Diseases of the periodontium start in general with the recession of the periodontal ligament (PDL) and leads to loosening of the tooth within the alveolar bone. The cementum and periodontal ligament play important roles in physiological tooth function. Therefore, cementum and periodontal ligament regeneration are critical for periodontal regenerative therapy. Decades of clinical...
According to estimations of the Global Cancer Observatory, over 2.2 million women were diagnosed with breast cancer in 2020, worldwide. [1] While most often requiring surgical removal of the affected breast tissue, breast reconstruction following mastectomy remains a challenge. [2] Conventional reconstruction techniques, using synthetic prostheses or autologous tissue, are accompanied with...
Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling....
Introduction
Cellular senescence is an irreversible cell-cycle arrest program that has been associated with numerous biological processes. While emerging studies have extended its role to tissue repair, the focus has been on the effect of the senescence-associated secretory phenotype (SASP) rather than the direct role of the program beyond its paracrine effect. Using a previously...
"Introduction: Synovial fluid is a viscous liquid found inside the joints of bones. This fluid helps in minimizing the bone to bone contact and facilitates movements of joints via lubrication. The key component of synovial fluid which gives its viscous property is hyaluronic acid (HA). Apart from HA it also consists of various proteins like albumins, gamma globulins etc. Synovial fluid has a...
Introduction. In modern medicine, the transplantation of mesenchymal stem cells (MSC) is utilized as a universal system for organism’s protection and renewal under normal and pathological conditions. However, there are only a few studies concerning the use of mesenchymal stem cells to treat respiratory viral infections. This study aimed to estimate the morphological direction of MSC action in...
Introduction. The employment of recellularized autologous extracellular matrices (ECM) as scaffold for the reconstruction of complex tissues like skeletal muscle has been recognized as a successful strategy for regenerative medicine. Compared to the application of synthetic patches, which represent the current standard of care for congenital neonatal malformations like omphalocele and...
Introduction:
The development of vaccines represents one of the most impactful milestones in the improvement of global health over the last 200 years1. After a first administration of an antigen, the delivery of a booster is usually required to potentiate the immunostimulatory properties of the antigen2. Despite the undeniable success of vaccines, delivery could be improved. The use of...
"Polymer scaffolds are playing an increasing role in tissue engineering (TE), although there is still a need to improve their biomimicry of cellular microenvironments, by having smart scaffolds with an active response, which can improve tissue regeneration. Ionic liquids (ILs) have emerged as an attractive option to achieve this due to the biodegradability and biocompatibility of many ILs, and...
Abstract
Tissue engineering (TE) combines both cells’ biology and engineering to develop bioactive biomaterials to treat tissue regeneration [1]. Among them, biomaterials with electric conductive properties have shown promising potential as bioactive cell substrates for tissue regeneration, especially for electrically active tissues, such as the skeletal muscle system [2].
Alginate hydrogels...
"Introduction
Hydrogels are hydrophilic cross-linked polymeric materials that have been widely studied in tissue engineering (TE) to mimic human tissues [1]. The functionality of electroactive tissues, such as cardiac, neural and muscle, strictly depend on electrochemical signaling between cells. Therefore, TE scaffolds interacting with those tissues should be designed with electroconductive...
Introduction
Extracellular matrix (ECM) of hard tissues in human body has a specific composition combining organic and inorganic fractions that determines their properties and function. Therefore, designing scaffolds for bone tissue regeneration we should consider hybrid materials providing proper mechanical and structural support. The focus of current study were scaffolds based on...
"Introduction
Wisdom tooth extraction is one of the most common surgeries carried out in the UK, and is notorious for causing post-operative complications. 1 in 6 patients experience a condition called alveolar osteitis “dry-socket” after wisdom tooth removal; a condition where the blood clot is lost and the extraction socket becomes painful. The condition is a serious problem and causes a...
Osteogenesis Imperfecta (OI) is an inherited connective disorder mostly caused by type I collagen
(Col I) mutations resulting in low bone mass and increased fracture incidence [1]. Type I collagen is the structural protein that maintains the mechanical properties of bone. To date, analysis of collagen structure has been conducted using either patient bone biopsies or animal (mice)...
"Introduction
Myocardial infarction (MI) is the main cause of mortality and morbidity worldwide. MI initiates a wound healing process resulting in a fibrotic tissue, characterized by random morphology and increased stiffness [1]. Currently, several advanced strategies based on regenerative medicine are under investigation and in vitro models of pathological cardiac tissue have attracted...
Tissue engineering strategies are widely used to model and study the bone marrow microenvironment in healthy and pathological conditions. Yet, while bone function highly depends on mechanical stimulation, the effects of biomechanical stimuli on the bone marrow niche, specifically on bone marrow adipose tissue (BMAT) is poorly understood due to a lack of representative in vitro loading models....
Introduction
Tubular tissues are ubiquitous in the body, from blood vessels and lymph ducts to bile and breast ducts. Evaluating drug efficacy for the treatment of pathophysiological conditions using in vitro models is crucial before initiating animal and clinical trials. A major problem with current in vitro models is the discrepancy between in vitro and in vivo results. This discrepancy...
"Introduction
Everyday thousands of people of all ages across the world are admitted to hospitals because of the severe injuries or malfunction of some vital organs [1]. Organ or tissue transplantation is a standard therapy to treat these patients. Irony of fact that many of these people will die due to the paucity of donor organs and high processing cost involved in organ transplantation...
Nowadays, the main approaches to engineer vascularized tissues are to develop biomaterials combining with cell-based therapy to achieve rapid vasculogenesis angiogenesis and anastomosis between engineered and host blood vessels. However, the thickness of engineered vascularized tissues in animals were still less than 1 mm, because the hydrogel becomes less permeable with increasing thickness....
Introduction
Hematopoietic stem cell and progenitor cell (HSPC) niches are provided by the bone marrow (BM) tissue, from where HSPCs ensure the blood cells production throughout individual’s life. In contrast to the murine counterparts, human HSPC niches remain poorly understood due to accessibility and ethical difficulties. In order to bypass these limitations, our lab has engineered...
INTRODUCTION: Liver diseases are becoming a significant public medical burden[1]. To overcome the lack of donor livers and high cost of therapy, this project aims to exploit a long-term culture system that maintains hepatocyte specific functions [2] and cell viability for liver regeneration using self-assembled peptide hydrogels to mimic the normal hepatic extracellular matrix (ECM). Previous...
Introduction
The subcutaneous space is an attractive alternative site for engineering vascular networks, since it provides relatively easy accessibility, minimal invasiveness, and potentially high transplant capacity. However, it’s also a poorly vascularized site that often fails to achieve the level of vascularization necessary to maintain function of thick grafts.1 Here, we patterned our...
"The space environment allows for research that simply cannot be done on Earth. It stimulates innovation, because terrestrial solutions may not work in space, but, at the same time, space-inspired solutions can be transferable to Earth.
The European Space Agency (ESA) is Europe’s gateway to space. Its mission is to shape the development of Europe’s space capability and to ensure that...
"Introduction: Soft tissue-engineered constructs (sTECs) require tailored dynamic changes in their structure-properties-process (SPP) relations to preserve their functionality throughout the tissue regenerative process. At the initial stages of regeneration, a highly interconnected architecture is recommended to accelerate plaque adhesion and blood clot formation. At later stages of...
"Impaired wound healing in diabetics particularly is a major healthcare problem, and new
therapeutic options are expected. The aim of the study was to evaluate the potential role of insoluble keratin-derived powder containing silver nanoparticles (FKDP-AgNP) in the full-thickness surgical skin wound model in diabetic mice. The scanning electron microscopy image showed that the keratin...
"Introduction: Severe skin lesions can be life-threatening conditions, especially in burnt patients. We recently described the UGRSKIN model of bioartificial human skin generated by tissue engineering as an ATMP1. Although preliminary clinical results are promising, the biofabrication procedure requires long periods of time due to the need of obtaining abundant keratinocyte cell populations...
Biodegradable magnesium alloys are promising candidates for temporary fracture fixation devices in orthopedics; nevertheless, its fast degradation rate at the initial stage after implantation remains as one of the main challenges to be resolved. ZrO2-based coatings to reduce the degradation rate of the Mg-implants are an attractive solution since they show high biocompatibility and stability....
"Introduction. Through guided differentiation, human-induced pluripotent stem cells (hiPSCs) offer a reliable and unlimited source of hepatocytes that are certainly proving themselves useful in numerous tissue engineering and personalized medicine applications. However, concerns persist regarding the lack of functional maturity and long-term maintenance in culture of hiPSC-derived hepatocytes...
Introduction: The use of nerve autografts remains as the gold standard method for critical nerve repair. However, due to their well-known disadvantage new nerve grafts are still needed. In this sense, decellularized peripheral nerve-derived extracellular matrices (ECMs) have emerged as a promising alternative, but these processes may affect the structure, composition and biomechanical...
Introduction Mesenchymal stem/ stromal cells (MSCs) represent one of the most extensively investigated adult stem cell populations due to their pro-regenerative activity observed following their application into injured tissues. Diabetes mellitus type 2 (T2D) is a serious civilization disease occurring frequently in western societies. The prolonged high glucose level in blood may cause damage...
Introduction
Recently, researchers have found increasing evidence that along with other mechanical cues of the cellular microenvironment, viscosity also has an influence on stem cell fate. However, it is barely studied how cells sense the viscosity of microenvironment. In this study, we explored the effect of viscosity of culture medium on osteogenic differentiation of human bone...
"Introduction: Spider silk (SPSI) as one of nature’s most fascinating materials has attracted vivid attention due to its remarkable performance in tissue regenerative applications by supporting nerve growth and nerve regeneration. Particularly for supporting the regeneration of large nerve defects, the biomaterial has proven to be incomparably successful. The material’s variability and the...
"Introduction: Cyclophilins are peptidyl-prolyl isomerases that regulate several biological processes. Importantly, cyclophilin-A promotes the remodelling of extracellular matrix (ECM) proteins by activating matrix metalloproteinases and is implicated in the correct folding of collagen fibres. Cyclophilin inhibition has shown beneficial therapeutic effects at various stages of liver disease,...
Introduction
Bone loss due to various infections, aging, tumors or genetic disorders is worldwide problem; moreover, not all defects can be regenerated by using today’s technologies. For this reason scientists construct artificial bone scaffolds which could provide new bone treatment strategy. Scaffolds surface biodecoration highly enhances their integration and allows to control damaged...
Introduction:
One of the main methods to investigate cellular function, including stem cell differentiation, pathological state, and drug responsiveness, is by analysing deposition of extracellular matrix (ECM). Current methods such as Western blot, mass spectroscopy, or immunostaining, either require the removal of cells and processing of the ECM prior to analysis, or only allow for the...
Introduction:
Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) play an important role in cell physiology, cell-cell communication, and immunomodulation. EVs are promising for regenerative medicine1, but their therapeutic effect in vivo is reduced due to their rapid clearance and short half-life2.
Injectable hydrogels emerged as great bioactive compound carriers due to...
"Introduction
Adipose-derived mesenchymal stem cells (hADMSCs) are a promising resource for regenerative medicine. They can be harvested directly from the patient with moderately invasive procedures and re-implanted without eliciting immune response. To date, several clinical trials are active in phase II-III, but new technologies are needed to make these therapies more efficient. In...
"Introduction. In the context of tissue engineering for regenerative medicine, the electrospinning technique consolidated itself as a valuable approach to fabricate tailored scaffolds. While its versatility lies in the possibility of controlling the process parameters, ambient parameters, and the properties related to the solvent system, the choice of the polymeric component itself results...
"*Purpose/Objectives: Scaffolds with a tissue-like characteristics and suitable physical properties are critical for tissue engineering and regeneration. 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) were commonly used for biomaterials because of their high biocompatibility and stability in the host tissue. Herein, we report porous poly(HEMA-co-MMA) scaffold for tissue...
Polysaccharide-based hydrogels have been developed in the fabrication of multifunctional microenvironments for tissue fabrication. In this study, two opposite charged polysaccharides including chitosan and hyaluronic acid conjugated with phenol moieties (PH) (CH-PH &HA-PH respectively were mixed at different ratios and utilized to enzymatic cross-linking in the presence of H2O2 as an...
Biocomposites made of poly(propylene carbonate) (PPC), a carbon dioxide (CO2) derived polymer, and a renewable polysaccharide are promising materials for several applications such as biomaterials and packaging. However, most of PPC-based biocomposites exhibit low mechanical and optical properties due to the inherent incompatibility between PPC and most other polymers. In this work, a novel...
Introduction: The management of long bone critical-size defects leading to nonunion remains a major clinical orthopaedic challenge. Mesenchymal stem cell (MSC)-based therapies are promising strategies for bone healing of critical-size defects. Preliminary studies suggested that implantation of Interleukin-4 (IL-4) overexpressing MSCs within a gelatin microribbon (µRB) scaffold during the early...
Computer modelling is applied to a wide range of engineering applications to predict the outcome of a physical system. In bioengineering, additive manufacturing (AM) technologies and computer modelling can be placed side by side to fabricate tissue engineering (TE) scaffolds and to study their behaviour under certain circumstances (e.g., the effect of shape, size, and porosity on mechanical...
Simultaneous flexibility, strength and toughness are exceptional characteristics of soft biological tissues which do not exist in man-made materials. Soft tissue-engineered meshes (sTEMs) should exhibit tissue-like mechanics and geometries for better performance and fit. However, the majority of current clinical meshes for soft tissue regeneration are conventional fabrics made by knitting or...
INTRODUCTION
In recent years, regenerative medicine is becoming more and more important, especially the field related to stem cell transplantations. In the body, the physiological niche microenvironment of stem cells (SCs), characterized by a unique combination of biomechanical, biochemical and biophysical properties, is a challenging research key. In this context, the micro-scaffold...
Introduction
Microfluidic cultivation platforms significantly improve the supply of tissue models in vitro. However, a key challenge is the sufficient distribution of oxygen and nutrients within a 3D construct. Here we demonstrate the use of collagen hollow filaments as a functional unit for the generation of a vascular structure in tissue engineering applications.
Methodology
The hollow...
Introduction:
The human bone marrow (BM) is home to Hematopoietic Stem Cells (HSCs) and Bone Marrow Stromal Cells (hBMSCs) which are known to contain skeletal stem cell populations. Whereas the HSC compartment is well characterized, the identity and function of the hBMSC populations remain obscure and requires thorough investigation. A better understanding of the BM and the accommodated cells...
Introduction
Large infection spreading rates combined with increasing microbial resistance to antibiotics remain one of the biggest healthcare challenges. In this context, biomaterials based on natural biopolymers with antibacterial properties have recently come to the fore as potential candidate vehicles as both preventative measures and treatments of severe infections. In this study,...
Introduction: The reconstruction of the abdominal wall after abdominal surgery [NN1] results in the loss of tissue biomechanical properties and the occurrence of surgical site infections (SSI). Current available solutions (i.e. implantation of surgical meshes) can restore the abdominal tissue wall biomechanics although inducing significant clinical complications. Bioengineered spider silk...
Introduction: Immobilization of cell adhesive proteins on the scaffold surface has become a widely reported method for improving the interaction between scaffold and cells [1]. Immobilization is performed using various methods based on chemical binding or physical interaction between biomolecules and polymer. Benefits, as well as weak points of both ways, are under discussion in the literature...
"Introduction
Tissue engineering employs a variety of different cell friendly platforms capable of supporting and enhancing cell growth and proliferation [1]. Bone and endothelial tissue interaction is closely connected since bone formation depends on vascularization [2]. This work reports on the fabrication of microspheres as biocompatible carriers for the controlled delivery of the growth...
Introduction
Poly(vinyl alcohol) (PVA) may be used in 3D printing as a sacrificial material in the formation of tissue engineering constructs with complicated architectures. Our research aims to combine 3D printing scaffold fabrication based on PVA as a sacrificial material with enzymatic mineralization and chemical crosslinking of hydrogels, which are done by incorporating specific chemicals...
Introduction
Bone tissue is a vascularized, highly specialized, and hierarchically organized tissue. Nowadays, Tissue Engineering is challenging to recapitulate the structural complexity of physiological bone extracellular matrix (ECM), and biomaterials have been widely investigated [1]. Herein, methacrylated gelatin (GelMA) was largely involved since physico-chemical and mechanical...
Introduction: Damage of the sclerocorneal limbus may lead to limbal stem cell deficiency (LSCD), loss of corneal transparency, and blindness. Keratoplasty is the standard treatment for corneal transplantation disorders, but it is contraindicated in cases with LSCD or limbal damage1, which are very difficult to manage. Generation of a biological substitute of the sclerocorneal limbus could...
Articular cartilage has a poor capacity for self-repair, consequently, defects are one of the major causes of immobility and poor quality of life for millions of individuals worldwide. Damage to articular cartilage can be caused by trauma, ageing, genetic factors and degenerative diseases such as osteoarthritis and is often irreversible without surgical intervention. The current clinically...
Introduction. Osteosarcoma is the most common type of bone cancer diagnosed especially in children and young adults1. A combination of chemotherapy, radiotherapy and surgery is commonly used to treat this type of cancer2,3. In detail, chemotherapy is based on the use of molecules targeting the high cancer cell proliferation metabolism such as Platinum-based drugs that binds nuclear DNA upon...
Hydrogels derived from extracellular matrices (ECM-gels) have been described with promising features to promote tissue regeneration, since they preserve several components of native tissues. However, their weak mechanical properties impair ECM-gels use in load-bearing applications. Previously, we have shown that the incorporation of oxidized forms of graphene, one of the strongest materials in...
Cartilage is a non-vascular connective tissue composed of specialized cells – chondrocytes. The lack of blood vessels results in limited cartilage self-regeneration capabilities. While various options are available to treat osteoarthritis, no current method can restore the mechanical function of the original hyaline cartilage. Therefore, herein we address, hyaline cartilage regeneration issue...
Wounding affects us all, yet the mechanisms of healing are still a partial mystery. In particular the events immediately unfolding when a tissue is wounded are difficult to capture, and are thus understudied und incompletely understood. Studying wounding responses in ex vivo skin is an elegant strategy to explore immediate wounding responses. Using ex vivo skin from both human and pig has...
"Introduction: Minimally-invasive prenatal interventions which aim to ameliorate fetal developmental defects have become a clinical reality and are currently performed for a variety of life-threatening complications. However, in up to 30% of the cases, the intervention translates into preterm birth and its associated negative consequences. The puncture created in the fetal membranes (FMs)...
Although oral formulations of anticancer chemotherapies are clinically available, the therapeutic action relies on drug absorption, being inevitably accompanied with systemic side effects. It is thus desirable to develop oral therapy systems for the local treatment of colon cancers featured with highly selective delivery and minimized systemic drug absorption. The present study demonstrates...
The emergence of human induced stem cells (hiPSCs) circumvents the ethical controversy of human embryonic pluripotent stem cells(hPSCs), introducing great feasibility in stem cell research. There are various methods to trigger the cellular reprogramming process, including viruses, plasmids, episomal plasmids, RNAs, proteins, and small molecules. mRNA-based reprogramming has up to 4% efficiency...
INTRODUCTION. Articular cartilage has excellent biomechanical properties, but due its avascular nature and the low proliferation capacity of mature chondrocytes, the regeneration process usually produces fibrocartilage scars, with worse biomechanical properties. For this reason, articular cartilage traumatic injuries and degenerative pathology are frequent causes of pain and...
"During the last decade, bioprinting technology has gradually made tremendous progress in manufacturing complex cell-laden hydrogel-based constructs especially for advanced 3D in vitro models. However, most models still lack full complexity. The combination of multiple state-of-the-art printing processes is currently expected to make up for this shortcoming and to improve the outcome after...
Introduction: Emerging as one of the major causes of disability and death, respiratory diseases affect millions of people worldwide.
To date, despite numerous efforts and clinical attempts, there are no effective treatments to repair long-segment defects, and a standard procedure is still missing.
Among the ventured clinical applications, Tissue Engineering (TE) approaches hold the potential...
Mesenchymal stromal cells (MSCs) possess immunomodulatory abilities that make them a promising candidate for the treatment of immune-mediated diseases, particularly those with an autoimmune component. We have recently shown that preconditioning human bone marrow (BM) MSCs with Vadadustat – hypoxia mimicking agent, may constitute a valuable approach to improve the therapeutic properties of...
Symposium: Cell-rich constructs for tissue engineering.
Introduction: The development of in-vitro model of skeletal muscle regeneration is extremely challenging. Human Bone Marrow-derived Mesenchymal Stem Cell (hBM-MSCs) and human Myoblast co-culture with growth factor supplementation has been described for in vitro myogenic commitment [1-2]; among them, b-Fibroblast Growth Factor (b-FGF) was...
Mesenchymal stem cells (MSCs) represent a promising tool for tissue engineering and regenerative medicine. However, their procurement often requires invasive medical procedures. Urine-derived stem cells (UDSCs) display similar properties to MSCs, and their sampling and further processing are non-invasive for donors. The goal of this study was to analyze their morphology and selected biologic...
Introduction
Nanofibrous materials have the potential to be used in medicine, the most mentioned areas being topical applications, e.g., skin wound healing. Promising materials are biopolymers such as hyaluronic acid (HA), which is a part of the extracellular matrix and plays an important role in the inflammatory and granulating phase of wound healing. Nevertheless, HA is highly hydrophilic...
Introduction: Tissue engineering approaches appear highly promising for the regeneration of injured bone tissues. This strategy combine three essential components such as: scaffolds, mesenchymal stem cells (MSCs) and growth factors and is based on the culture of stem or progenitor cells on scaffolds in order to generate new bone by osteoinductive cue. Recently bioengineering has been focused...
"
Bone is one of the most important composite building materials, which is the main component of the human skeleton [1]. It is estimated that the total number of fractures in the European Union will increase from 2.7 million in 2017 to 3.3 million in 2030. The resulting annual costs associated with fractures are expected to increase by 27%. Furthermore, as the population ages, this figure is...
"Intracellular delivery of advanced biological and supramolecular agents holds great potential for fundamental and translational biomedical research, but it is staggeringly complex due to the natural biological barriers that have evolved to protect the cell. A plethora of viral, chemical, and physical approaches have been developed to facilitate delivery of biomolecules into different cell...
Hydrogel materials are widely used in medicine and tissue engineering due to their similarity to the natural tissues of the human body. They are well known for their high biocompatibility and swelling - the ability to absorb large amounts of water. These properties determine the possibility of the use of hydrogels in the regeneration of cartilage tissue. In order to enhance regeneration...
Title: HYDROGELS FOR 3D EXTRUSION PRINTING OF GRADIENT SCAFFOLDS
Rency Geevarghese1, Joanna Żur-Pińska1, Małgorzata Włodarczyk-Biegun1,2 *
1Biofabrication and Bio-Instructive Materials, Biotechnology Center, The Silesian University of Technology, B. Krzywoustego 8, 44-100 Gliwice, Poland.
2Polymer Science, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747...
Introduction
The skin, as the outermost barrier of the body, is exposed to threats from the external environment including injuries, oxidative stress and UV irradiation. Therefore, efficient systems of repair and antioxidant protection of damaged skin that are achieved by an extraordinary mechanism involving the interaction of cells, cytokines and growth factors are vital for survival. In the...
Introduction: Tendon injuries represent a significant personal and socioeconomical burden whose medical treatments remain insufficient to restore normal functionality. Tendon healing is often impaired, contributing for the lesion severity, risk of re-ruptures and ultimately tendon dysfunction[1]. Persistent inflammatory cues have been associated to the development of tendon pathologies, and to...
Introduction: In the last decade, the interest in understanding perinatal tissues, including the human umbilical cord, have exponentially increased due to the plasticity, differentiation, and immune modulatory properties of these tissues1,2. Advances in the comprehension of the biology of human umbilical cord and their cells, will contribute to establish their potential use in tissue...
[Introduction] Fibroblasts are the major cells that consist of connective tissues in animal tissues and are known as the main extracellular matrix (ECM) production cells to maintain the tissue physical properties. Although they are cells that are famous and frequently found in our body, their biological mechanisms, especially the differences from other similar fibroblastic cells are still...
Introduction
Implant related infections result from persistent bacteria adhering to the biomaterial surface before, during, or after surgery, enabling colonization and biofilm formation on the implant [1]. On average, 4% to 10% of implant surfaces are estimated to be contaminated with bacteria, however, the infection rate can be as high as 30% in intensive care units in developed countries,...
Introduction: 2D pnictogens, including bismuthene, have recently emerged as new members of the ever-increasing 2D family thanks to their exceptional electronic, topological, thermoelectronic, and optical properties.
Here we present a 2D bismuthene synthesized from the 3D bulk bismuth involving a surfactant-assisted chemical reduction method to improve its magnetic properties...
"INTRODUCTION: Diabetic foot ulcer is a common chronic inflammatory condition associated with individuals with type II diabetes. It is characterized by delayed or absence of wound healing eventually leading to gangrene formation necessitating limb amputation. Despite current management and treatment strategies, one in three wounds fails to heal. Hence, there is a pressing need to develop novel...
Injuries to peripheral nerves is a common health problem, often resulting in sensory and motor dysfunction in respective parts of the body. One of the most important facilitators of the regeneration process are Schwann cells (SCs), which basement membrane is chiefly comprised of laminin. Extracellular vesicles (EVs) are considered playing an important role in the intercellular communication...
Alginate, a natural linear polysaccharide polymer, extracted from brown seaweed, is extensively applied due to its biocompatibility, all- aqueous ease of handling and relatively low costs. Alginate easily forms a hydrogel when crosslinked with a bivalent ion, as calcium. However, Alginate hydrogel holds low mechanical properties and it is cell-inert. To overcome these drawbacks and to improve...
Statement of purpose:
Zinc (Zn) has been proposed as a novel biodegradable metal thanks to its essential physiological and biological roles and its promising in vivo degradation rate [1, 2]. Compared to Mg alloys and Fe alloys, the degradation behaviour of Zn alloys is more likely in line with clinical demand. One of the main factors limiting the extensive clinical application of Zn and its...
Introduction: Development of bioartificial substitutes of the human oral mucosa and palate is strictly dependent on the availability of human keratinocyte cells cultured from small tissue biopsies1. Although cell culture methods have been improved over the last years, epithelial cells typically show low proliferation rates and cell culture protocols should be improved for an efficient use in...
Microbial keratitis is a devastating vision-threatening ocular disease requiring immediate broad spectrum antimicrobial treatment to prevent scarring, corneal perforation, and/or endophthalmitis. In the progression stages, to reduce the burden on the immune system, keratoplasty is applied. Temporary patches usually are used until the microbial activity is over in order to preserve tissue...
"The dopaminergic system is vital for the control of both motor control (nigrostriatal pathway, A9 dopaminergic neurons), and reward (mesocorticolimbic pathway, A10 dopaminergic neurons). Both pathways are associated with different types of diseases: the nigrostriatal pathway is most commonly associated with Parkinson’s disease, whereas the mesocorticolimbic pathway becomes dysregulated in...
"Introduction. Worldwide cancer remains the second-most common cause of death; among bone cancers, Osteosarcoma (OS) is the most common type diagnosed especially in children and young adults1. The lack of specificity for the Cancer Stem Cells (CSCs) subpopulation has been recently identified as the main limitation in conventional therapies2. Moreover, the traditional two-dimensional (2D) in...
INTRODUCTION: Osteoblasts (OBs) and osteoclasts (OCs) interaction have an important role in bone remodeling [1]. Thus, coculture with both bone cells (OB-OC) is needed to achieve a better understanding of the material-cell interaction and the impact on Mg degradation for its potential use as a biomedical material. The aim of this study was to analyze the surface morphology and dynamic changes...
Introduction,
Clinically, reconstruction of a nerve gap can be performed with a nerve graft (carrying the risk of donor site morbidity) or with nerve guidance conduits (NGC), which are only applicable for small nerve defects. Both options are associated with poor outcomes for patients. Failure of current NGC to support regeneration across large defects (> 3cm) are thought due to a lack of...
Introduction: As a reliable alternative to autografts, decellularized peripheral nerve allografts (DPNAs) maintain the complex natural structure of native nerves minimizing the immune response. However, there is currently a lack of decellularization methods for peripheral nerve that remove cells minimizing any adverse effect in extracellular matrix (ECM) that overcoming the autograft results....
In previous decades, biomedical research has focused on the development of biomimetic and biocompatible materials, that do not cause any adverse reactions in the human body [1]. Synthetic materials are already widely used, but usually lack the necessary bioactive cues to promote a specific cellular response. Also, the degradation of these materials can cause toxic side effects....
Introduction
Mesenchymal stem cells (MSCs) are self-renewing, non-specialized, multipotent cells with great potential to differentiate into various tissue cells. Due to their secretion activity, migration, adhesion and homing abilities, MSCs are currently highly investigated stem cells and the one most commonly used in regenerative medicine. The use of adult MSC is still challenging, since a...
Introduction:
Dysregulation of glycosylation and metabolism are associated with pathological inflammation across various biological tissues1. Research into this dysregulation in the cornea has indicated that inflammation can induce changes in the structure and composition of corneal glycans2. An improved understanding of these alterations and the metabolic pathways leading to glycan synthesis...
Introduction. Interleukin 10 (IL-10) is anti-inflammatory cytokine that plays central regulatory role in immune-mediated inflammation caused by viral infection. The purpose of this work was to study the action of IL10 on the efficiency of cell therapy in a mouse model of influenza pneumonia.
Methodology. We used an experimental model of influenza pneumonia obtained by intranasal infection of...
Multipotent mesenchymal stromal cells (MSC) represent a promising therapeutic tool for tendon regeneration. They are capable of tenogenic differentiation, which is one of the mechanisms contributing to the regenerative effect of MSC after transplantation into tendon lesions and is furthermore required for tissue engineering approaches. Tenogenic differentiation is most typically induced by...
Type 1 diabetes (T1D) is an autoimmune disease that leads to the destruction of pancreatic islets, resulting in the deficiency of insulin secretion. The current treatment is a daily insulin injection regimen, which negatively affects the quality of life for T1D patients and is difficult to manage over an entire lifespan. Therefore, an alternative treatment – islet transplantation within...
Three-dimensional organoid culture offers great promise for precision medicine in cancer. In this study, we describe label-free imaging procedures including Fluorescence Lifetime Imaging Microscopy (FLIM) and Raman microscopy allowing in situ cellular analysis and metabolic monitoring of drug treatment efficacy. Primary tumor as well as urine specimens were utilized to assemble a biobank of...
Suspension-type cells, which do not require scaffold adhesion during their culture, is commonly regarded as cells derived from blood cells. In bio-pharmaceutical researches, antibody-production cells are also another major cell known as suspension-type cells. However, by the recent tissue engineering advancements, more and more types of suspension-type cells are required for cell therapy....
"Introduction
Huntington’s disease (HD) is a progressive neurodegenerative disorder with autosomal-dominant heritability characterized by the aggregation of mutant huntingtin (mHTT) protein. HD is described by the region-specific neuronal degeneration of medium spiny neurons (MSNs) in the striatum, elevated Ca2+ signaling, and dendritic spine pathology. However, the pathway connecting...
Introduction: Vitamin C (ascorbic acid) is a potent antioxidant and a crucial co-factor of many enzymes, including Fe2+ and alpha-ketoglutarate dependent dioxygenases such as TET (ten-eleven-translocation) proteins involved in active DNA demethylation. TET enzymes (TET1, TET2 and TET3) are able to oxidize 5-methylcytosine to 5-hydroxymethylcytosine and subsequently to 5-formylcytosine and...
Bone is constantly exposed to a range of macro-scale loading which creates a complex mechanical microenvironment for its resident cells. One such mechanical stress generated is hydrostatic pressure (HP) which plays an important role in cell function and fate determination. Although HP is a constant mechanical cue for bone resident cells, little is known about the effect of this external...
Purpose: To investigate the effect of Losartan on articular chondrocyte hypertrophy in a monolayer culture under chemically induced hypoxia with CoCl2.
Materials & Methods: The 2nd passage of human knee chondrocytes was used to determine the cell viability in response to the treatment with Losartan or CoCl2 in the following concentrations 10-4 – 10-12 M. Chondrocytes were seeded in a...
"Introduction:
Tissue engineering has the purpose to find a resolutive treatment for unsolved pathologies, as tendon disorders, taking advantage of cell-free approaches [1]. Since tendinopathies have been related to persisting inflammation state, the application of immune regenerative strategies is getting attention by exploiting the immunomodulatory potential of stem cells and their...
The growing interest in finding the best way to strengthen Mg alloys has recently focused on the development of Mg-Y-Zn alloys with long-period stacking ordered (LPSO) structures [1]. The microstructure of Mg-Y-Zn containing LPSO structures formed during plastic deformation was found to be beneficial in terms of mechanical properties [2]. The goal of this work is to investigate the role of...
Introduction: Biomechanical features and osteogenic properties of magnesium implants make them suitable for orthopedic applications. [1] Commonly used in vivo methods to investigate tissue response, such as histology and gene expression of peri-implant tissue, are terminal procedures that give a limited temporal and spacial view on the organism response to the implant. [2] Thus, systemic...
Introduction. Bone is the second most commonly transplanted tissue. The problems with allografts and xenografts as substitute for original tissue are associated with the graft loosing, inflammation and osteolysis or the death of bone tissue, which only adds to the existing damages [1,2]. In order to solve these shortcomings, tissue engineering have suggested a number of potential therapeutic...
"Introduction: Bottom-up developmental engineering is showing promising results in skeletal tissue engineering1. In this approach, microtissues are formed from periosteal cells, the main contributors in the formation of the cartilaginous fracture callus. These microtissues can be chondrogenically differentiated towards hypertrophy resulting in a cartilaginous template in vitro which can be...
Material-Assisted Bioengineering Strategies for Osteochondral Defect Repair
Constance Lesage, Marianne Lafont, Pierre Guihard, Pierre Weiss, Jérôme Guicheux, Vianney Delplace
*Theses authors contributed equally to this work
Key words: osteochondral defect, cartilage, subchondral bone, regenerative medicine, biomaterials, cell therapy, biologics
The osteochondral (OC) unit,...
Introduction: Pancreatic cancer has the lowest survival rate among the common cancers, mainly due to its symptom-free progression and the advanced stage of the disease at the time of diagnosis. The response to current treatment strategies is low, mainly due to the extensive desmoplasia and fibrotic extracellular matrix (ECM), which acts as a barrier against efficient drug delivery.
One...
The technology of 3D printing of bionic organs gives an opportunity to solve the problems of classical transplantology, such as the shortage of organs, complications of immunosuppression or rejection. After printing, the bionic pancreas requires an optimal environment conditioning the process of its maturation, which consists in the colonization of the produced vessels with endothelial cells...
"Introduction
It has been shown for many connective tissue types that substrate orientation can control collagen and ECM deposition. This has been used to engineer tissues with aligned fibril structures such as tendon. In cortical bone, collagen is organised into a lamellar structure with highly aligned collagen sheets packed into a “twisted plywood” configuration, however, reproducing this...
"Hydrogels are considered as very promising materials to be used as scaffolds in tissue engineering. Their relatively tunable mechanical properties make them particularly suitable for different tissues including vascular ones. It is well known that, during the regeneration phase, the mechanical properties of the scaffolds can play a relevant role in cellular growth and adhesion.
When...
3D bioprinting is a promising technology to fabricate complex tissue replacements layer by layer through the deposition of cells and biomaterials in a predefined path. It allows us to fabricate complicated geometries that are impossible to obtain through conventional manufacturing methods [1]. Before printing, a computational design for the intended tissue construct needs to be generated...
Introduction:
The in vitro differentiation of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to chondrocytes is mainly driven by the exogeneous administration of transforming growth factor β (TGF-β)[1]. Multiaxial load-induced activation of TGF-β1 (TGF-β1), which is secreted by the cells in a latent form has been shown to drive chondrogenesis[2]. In the present work, we apply a...
Melt electrowriting (MEW) has been demonstrated as one of the few biofabrication modalities capable of forming extremely thin micron-sheets for tissue engineering applications (TE). This advantage has been applied to produce planar scaffolds that mimic the tissue in patient-specific anatomical structures e.g., bone and cartilage. Despite the progress in the field, there is a need for further...
Large bone defects remain a clinical challenge to be solved via emerging 3D scaffolds. For effective treatments, the bone scaffold should satisfy competing mechanical, biological, and chemical functions presenting a challenging design problem. Besides mainstream experimental studies, computational efforts exist in literature presenting scaffold designs with primarily optimized geometries...
Introduction
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for malignant blood diseases. However, long-term results are limited by the high morbidity and mortality associated with the development of graft versus host disease (GVHD). The use of mesenchymal stem cells (MSCs) has emerged as a safe and effective therapeutic option for GVHD due to its...
Mesenchymal stromal cells (MSCs) have shown great promise in experimental traumatic brain injury (TBI), conferring protection mainly through the release of bioactive factors (secretome). In vitro models, mimicking the in vivo condition in a simpler but representative environment may be fundamental to investigate secretome mechanisms of action. Nonetheless, TBI research lacks relevant 3D in...
Introduction
The secretion of therapeutic factors and extracellular vesicles (EVs) by mesenchymal stromal cells (MSCs) gained much interest for their benefits in the regenerative medicine field. Indeed, the in vitro multipotency of these cells and the secretion of both angiogenic and immunomodulatory factors suggest a role in tissue repair and regeneration. However, during culture in...
INTRODUCTION
Despite big efforts and capital invested, drug commercialization is severely hampered by high attrition rates impacting all development phases. Cardiac-side effects are the fourth cause of post-marketing drug withdrawal and stand behind almost 30% during the pre-marketing phase. With the blame on current testing systems, the generation of affordable and more representative...
"Introduction: Musculoskeletal diseases include more than 150 pathologies and have been reported to affect 1.71 billion people worldwide (1). Among the different conditions described, the number of cases of chronic tendinopathy and tendon/ligament injuries has reportedly increased, mainly due to the rise of life expectancy in many countries (2). The currently used therapeutic tools mainly...
The interface between bones and connective tissues, i.e. cartilage, ligament and tendon, is characterized by changes in cell phenotype and matrix composition and organization. These changes result in graded mechanical properties that allow the transmission of load without creating stress concentrations. In some interface regions, differences in mechanical properties, such as stiffness, can...
Proper, consistent and correct biomechanical characterization is very important for 3D bioprinted scaffolds. Conventional approach foresees pre-selection of the material model and fitting experimental data to quantify properties in time and spatial scales. For injectable biomaterials the interaction of the biomaterial and the system as well as various dissipative phenomena (often uncontrolled)...
Idiopathic pulmonary fibrosis (IPF) is a degenerative and fatal disease, characterised by scarring of lung parenchyma and loss of respiratory function. Globally, this disease affects approximately three million people, and carries a typical life expectancy of 3-4 years at the point of diagnosis [1]. IPF is now considered to arise as a result of chronic damage to the alveolar epithelium,...
Introduction: YAP/TAZ complex is considered to be the main player in the mechanotransduction process. It shuttles between cell nuclei and cytoplasm depending on the stiffness of the growth substrate, dimensionality and cell shape. Stem cells in their natural environment, called niche, grow in three dimensional soft tissue but in standard in vitro culture are maintained mostly on flat stiff...
"Unresolved inflammatory responses in chronic disorders such as diabetes, cancer, cardiovascular diseases, among others, often drive the onset of non-healing wounds. Endothelial cells (EC), the population of cells lining the inner layer of blood vessels, become dysfunctional under the pathophysiological context of chronic disorders and undergo endothelial-to-mesenchymal transition (EndMT),...
"Introduction
Acute kidney injury (AKI) is an independent risk factor for end-stage renal disease (ESRD) and death and is characterized by a sudden failure of renal function. The standard approach to treat AKI is mostly supportive in nature. Stem cell therapy is a promising approach in regenerative medicine and has shown to work through multiple mechanisms to effect tissue repair. Mesenchymal...
So far, most organ and tissue damage resulting from genetic defects or trauma is treated with either pharmacologically or surgically. This is performed through the use of appropriate drugs or, in more severe cases, organ transplantation. However, over the past few years, biomaterials have increasingly gained importance in materials science with great hopes for solving tissue and organ healing...
Introduction
Skeletal muscle (SM) tissue engineering aims to achieve a mature SM tissue in vitro, by combining precursor cells, suitable substrates and the right stimuli to facilitate cell growth and differentiation into the desired phenotype. In this field, polymeric thin films are attractive due to their small thickness (from hundreds of nm to some μm), flexibility, adhesiveness,...
The use of xeno-free (animal origin-free) hydrogels to support the growth of cells significantly increased in the recent years. The advantage of these materials in comparison with animal derivates is the reproducibility of structural, mechanical and biological properties and, additionally, overcoming of potential immunological complications and disease transmission in vivo. Many novel...
INTRODUCTION: Millions of bone reconstruction operations are conducted every year. A promising alternative to autologous bone grafts are customized bone scaffolds. Biofunctional custom implants fills the defect in the tissue and carry mechanical loads. The presence of groups with hydrophilic properties (e.g., -OH) on biomaterial surface is preferred. For this reason, the modification of the...
"Hydrogels are among the most desired biomaterials due to their ability to mimic the native extracellular matrix (ECM) of tissues, cytocompatibility, multifunctionality, tunable gelation, and resilient mechanical properties 1,2. Hydrogels hold the particularity of being responsive to different stimuli (e.g., stress, temperature, pH, and light), which makes them suitable to be applied the...
Combining upconversion nanoparticles (UCNPs) and UV-sensitive polymers to form a drug delivery system (DDS) is a promising strategy to circumvent drawbacks of direct UV excitation in clinical applications. This study tuned up core-shell UCNPs with shell thickness of 6 nm and emission wavelength falling in the ultraviolet region at 350 nm under near-infrared (NIR) light irradiation at 980 nm....
Introduction: Electroactive smart materials are increasingly being used for tissue regenerative applications. Piezoelectric polymers, such as poly(vinylidene fluoride) (PVDF), are one type of electroactive materials that generate electrical potential fluctuations simply by applying mechanical pressure to the material, without the need for additional power sources. The use of piezoelectric PVDF...
Introduction: In the last two decades research has been focused on the development of biologically-derived matrices for reconstructive medicine[1]. Decellularized tissues from a xenogeneic donor represent a growth-friendly environment for cells of different species, including human, lacking most of the immunogenic components[2]. Decellularized porcine liver resembles the human counterpart and...
Introduction: Tissue decellularization methods allow obtaining new sources of biological scaffolds obtained from natural tissues and organs1,2. Although decellularized scaffolds can be useful, it is well known that their regenerative potential is significantly improved after recellularization. In the present work, we evaluated the potential of several cell sources to recellularize a xenograft...
"Introduction
Nowadays, soft tissue damage are typically replaced by grafts from other body parts. However, tissue grafting can be problematic due to the need for several surgical procedures or lack of sufficient tissue material. Recently, hydrogels have emerge as an alternative treatment for tissue regeneration. Specifically guanosine-based hydrogels show unique self-assembly properties...
Introduction: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare autosomal inherited skin blistering disorder caused by mutations in the type VII collagen gene (COL7A1). The large size of COL7A1 is a big delivery challenge for both viral and non-viral vectors and seriously hindered the development of therapeutic gene replacement therapy for RDEB. Our group has developed a series of...
In skin research, 2D monolayer in vitro models provide only limited fields of application as they do not sufficiently mimic physiological properties. Since in the spirit of 3R’s (Replacement, Reduction, and Refinement) animal models are to be avoided, new approaches like 3D skin equivalents (SE) are needed to close the in vitro/in vivo gap. Cell culture inserts to produce SE are commercially...
Glioblastoma (GBM) is the most common (60-70% of primary brain tumours) and the most malignant of the glial tumours. Although current therapies remain palliative, they have been proved to prolong overall survival. The effectiveness of temozolomide (TMZ) chemotherapy is limited by the serious systemic and dose-related side effects. Therefore, the primary goal of the presented studies was the...
"Prostate cancer is the most life-threatening cancer for men with high incident and mortality rates, accounting for 1.4 million cases worldwide in 2020 with around 52,000 new cases in the UK every year. The progression and malignancy of prostate cancer have been linked with enhanced fatty acid utilisation that may be driven by the need of the cancer cells for energy to support growth and...
Interleukin 7 (IL-7) is an immune cytokine that plays a critical role in the maturation and homeostasis of T and B-lymphocytes. The absence of IL-7 significantly affects the proliferation of early lymphoid progenitor cells and leads to the development of severe combined immunodeficiency syndrome. To date, there are active studies of recombinant IL-7 as a means of restoring the immune system of...
Tissue engineering as a field may benefit from progressively implementing and spreading the use of standards, conceived to support the repeatability, replicability and efficient comparing of research results among experts in the field worldwide. Considering that scaffolds play a fundamental role in many tissue engineering strategies, it would be interesting to count with an internationally...
Natural scaffolds derived from living tissue have been used in clinical applications. They provide similar architecture and composition to the target tissue and can be remodelled as desired. However, they still have some drawbacks as there is a risk of disease transmission and may require additional surgery. Therefore, extracellular matrix (ECM) based biohybrid scaffolds have been developed...
Introduction: Cell culturing of human cells used in oral mucosa and cornea tissue engineering can be optimized by using three-dimensional cell culture platforms1. In general, these systems comprise an extracellular matrix where cells can be cultured in a 3D spatial microenvironment able to simulate the physiological conditions in which cells are found in vivo, including cell-cell and...
Background: The treatment of bone defects, in maxillofacial surgery and orthopedics, represents a major public health challenge. Autologous graft remains the "gold standard" treatment, but the availability of grafts is limited. Bioactive materials, such as silicate-based bioactive glass (Bioglass®), are among the bone substitutes the most widely used as alternatives, for their osteogenic...
INTRODUCTION
Mesenchymal stem cells have contributed to the continuous progress of tissue engineering and regenerative medicine. Among different mesenchymal stem origins, the ones derived from adipose tissue possess many advantages including the ease of tissue harvesting, self-renewal potential and rapid population doubling time. Adipose derived stem cells (ADSC) have multipotent ability and...
INTRODUCTION: Mesenchymal stem cells (MSCs) are able to differentiate into osteogenic lineage and promote bone regeneration. However, direct cells transplantation into damaged tissue is not efficient to cover large bone defects. This problem could be solved by biocompatible scaffold support. Therefore, bone tissue engineering constructs based on a biomaterial scaffold, MSCs and osteogenic...
"Introduction:
Stem cells-based therapy has emerged as a new strategy within the field of regenerative medicine, proving its effectiveness in tendon regeneration [1]. Amongst the stem cell sources, Adipose-Derived Stem Cells (ADSCs) can differentiate towards the tenogenic lineage and modulate the inflammatory environment [2]. However, the mechanisms through which ADSCs promote tendon healing...
OXIDATIVE STRESS RESPONSE IN ADIPOSE-DERIVED MESENCHYMAL STEM/STROMAL CELLS
Tawakalitu Okikiola Waheed, Olga Hahn, Kaarthik Sridharan, Nina Gehm, Caroline Moerke, Kirsten Peters
Introduction: Adipose tissue-derived mesenchymal stem/stromal cells (adMSC) are shown to support wound healing due to their regenerative and immunomodulatory capacities. However, cell survival in the specific...
Structurally patterned materials offer various options for guided cell behavior. Cell behaviour can be guided by patterning spatially discretized biochemical, topological or mechanical properties or combinations thereof. Patterned materials allow to integrate multiple characteristics in single materials, resembling an anisotropy found in endogenous tissue regeneration. Previous studies using...
Introduction
Osteoporosis is a disease that interferes with bone homeostasis making the bone weak and susceptible to fractures. One of the areas affected is the pelvis, whose fractures force the patients to undergo invasive surgeries and long bed recovery.
Here, we aim at fabricating an electrospun composite scaffold based on PEOT/PBT and loaded with particles to promote bone regeneration as...
2D (two-dimensional) monolayers of Caco-2 cells, on Transwell inserts, have been widely employed to assess drug permeability and absorption of drugs across the intestine. However, 3D (three-dimensional) in vitro tissue models are more physiological relevant as they can simulate interactions with the extracellular matrix and, therefore, better recapitulate the complex in vivo intestinal tissue...
Supercritical CO2 (SCCO2) technology was used to eliminate the cells, fat and non-collagenous materials while preserving a native collagen scaffold as a biomedical device for bone defects. We used porcine matrix bones with 3D CAD/CAM carving to reconstruct a personalized, wide range and complex-shaped bone. In oral cancer patients upto 30–50% of need mandibulectomy and autologous fibula...
Along with the continuous development of civilization and the intensive technological progress, the diseases of civilization are becoming a growing problem. The most common diseases of civilization include cardiovascular diseases, cancer and osteoporosis [1]. According to the International Osteoporosis Foundation, the problem of osteoporosis affects approx. 200 million people. Osteoporosis is...
"Introduction
Adipose-derived stem cell (ASC) are increasingly recognized as a vital tool for cell-based therapy. Hypoxic pre-conditioning of ASCs provides thier functional enhancement and makes the cells more attractive for translational science. Recently, ASCs from livestock animals have gained increased attention due to their promising role in developing regenerative medicine protocols...
Introduction. Glioblastoma is a very aggressive type of cancer with a very poor life expectancy for patients and breast cancer often metastasizes into the liver, lungs, brain, and, in 70% of cases, to bones[1,2]. Chemotherapy is largely used to treat cancer and it is based on the use of molecules targeting the high cancer cell proliferation metabolism[3]. Platinum (Pt) and three of its...
"Introduction
Guided tissue regeneration (GTR) is a surgical procedure that specifically aims to regenerate soft and hard periodontal tissues when they are irreversibly destructed. GTR requires special porous barrier membranes, preferentially degradable, capable of preventing soft tissue infiltration into the bone defect and simultaneously supporting bone regeneration. The aim of this study...
Introduction
Poly(alkylene citrate)s – (PACs) are widely studied as candidates to produce temporary medical devices such as blood vessel prostheses, wound dressings, drug delivery systems, scaffolds, and matrices for tissue engineering. The advantages of PACs are susceptibility to hydrolytic degradation and the possibility of modification with free radical scavengers, which are known to tune...
Although fibrosis is a natural process with a protective function in the body, it can lead to progressive disease and eventual loss of organ function. This pathology can affect different tissues, ranging from skin to the heart; indeed, lung fibrosis has been observed in COVID-19 patients. The proposed root causes of fibrosis are injury, infection and chronic inflammation, which leads to...
INTRODUCTION
Tendinopathy (also called tendinitis or tendinosis) is a tendon disorder resulting from repetitive motion in the affected area or during athletic activity.It is related to pain and swelling in the affected area, with decreasing mechanical strength and movement. [1] With the rapid growth of an aging population, there is an increasing incidence of chronic tendinopathy.Current...
Introduction: The growing requirements for tissue engineering results in the design of new materials, including polymer composites with various modifying phases. In addition, active substances can modify the properties of materials, and thus the human body's response. For this purpose, polymer-ceramic composites with various mesoporous glass (MBGs) modifying phases were designed. Numerous...
We proposed a new formation for fibrous mat fabrication from derivatives of polyvinyl alcohol (PVA) and gelatin (Gela) through horseradish peroxidase mediated crosslinking which provides sustain release of methylprednisolone (MP) as a therapeutic approach for SCI regeneration. The polymeric solution of PVA and Gela conjugated with phenolic moieties (PVAPh & GelaPh respectively) containing...
Introduction:
The pain and gradually progressing limitation of mobility are the main burdens of osteoarthritis (OA). Each year, an increasing number of people are affected by the OA. Meanwhile, despite the efforts of many scientific groups, the successful regeneration of cartilage tissue remains an unresolved issue. Amongst many therapeutic strategies, those involving hydrogels are one of the...
From 2020's WHO data, Ischemic heart disease is already the world's leading cause of death, and it also brings a high burden to the world. Nowadays, almost all clinical therapies based on supportive therapies, not is curative therapies, which cannot regenerate myocardial tissue. If using heart transplantation, there has not been resolved yet that donated hearts will be little supply and the...
[Introduction]
Breast cancer is one of the major lethal diseases. Surgery has been widely used to treat breast cancer. But surgery cannot resect all cancer cells in some cases, which may result in cancer recurrence. Recently, photothermal therapy, which is based on photothermal ablation of cancer cells, has been developed as a promising cancer therapeutic strategy. Until now, various...
"INTRODUCTION
Preterm birth one of the biggest complications in Obstetrics and is the case of life-long morbidities or even mortality of newborns. With advances in fetal therapy, the occurrence of operation-induced failures of fetal membranes (FM) ending in preterm birth is increasing. Responsible for this adverse outcome are the created defects in the FM that do not spontaneously heal....
Introduction: Numerous clinical trials in which MSC cells were used have lead to different results, not always as positive as expected. According to our hypothesis MSC can be replaced in some therapies by active factors they produce. Therefore, we decided to replace the primary MSC cultures with immortalized line derived from human adipose tissue (HATMSC1) to produce biologically active...
"Introduction: Chronic wounds represent a major burden in human society, and their prevalence is expected to increase due to the upward trend of an aging population, incidence of diabetes, and obesity. In Europe, one out of five hospitalized patients suffers from a pressure ulcer. Moreover, the costs associated with its extensive care treatments are high; about 25 billion dollars are spent...
"Introduction. Impairment of extracellular matrix (ECM) remodeling is observed in tumour microenvironment or fibrosis and results in excessive collagen production and/or its decreased degradation by metalloproteinases (MMPs). Due to its pivotal role in tissue architectures and functions, ECM components and the proteins that regulate ECM remodeling are thus promising therapeutic targets for...
Introduction: Synthetic hydrogels are a promising strategy to reproduce the 3D microenvironment of bone tissue. However, most of them lack the required bioactivity to actively influence cell fate. To this end, biochemical cues, such as integrin-binding molecules combined with growth factor derived sequences, may be installed on hydrogels to mimic bone extracellular matrix (ECM) [1-2], thus...
Introduction: Mesenchymal stromal cells (MSCs) have the potential to respond to injury and aid in repair and regeneration of damaged tissues. Bone marrow and adipose tissue are the major sources of MSCs for clinical applications. Previous studies in animal models suggested that the regenerative activity of aged stem cells/MSCs can be enhanced by exposure to biomimetic microenvironments. The...
3D printing, or spatial printing, is a modern, low-cost alternative to earlier manufacturing technologies. It involves printing layer upon layer of an object designed in an appropriate digital file. As inks in 3D printers are used various filaments, most often polymeric, in solid form, which are melted in the printer head. However, the medical industry is increasingly using hydrogels as inks...
Human bone marrow mesenchymal stromal cells (hBMSC) combined with biomaterials are currently used clinically for bone repair, but their bone formation kinetics are heterogeneous. The development of optimized pro-regenerative therapies requires a rigorous understanding of the molecular progression of regeneration. Here we report the divergent molecular events that drive hBMSCs toward fibrosis...
Introduction
Mammalian bone growth in length occurred through the process of enochondral bone formation through sequential chains of chondrocytes proliferation and differentiation at the growth plate (GP) 1. The endochondral ossification (EO) process is highly regulated to ensure normal post natal bone development at the epiphyseal growth plate (EGP) 2. The cascade of events during ED is...
Introduction. The long-term expected outcome after a hernia mesh repair is to create a framework in the prolapsed area that facilitates the development of mechanically robust, vascularized new tissue formations. Hernias of the anterior abdominal wall and vaginal prolapse are common and traditional suture repairs are associated with high rates of recurrence. Similarly, permanent meshes, while...
Tissue engineering significantly requires fresh approaches to achieve hierarchy of the targeted tissues in 3D forms where the feature size is not limited by diffusion. We are investigating interconnected toroidal tissue sheets made of MSCs co-cultured fibroblasts or ECs and utilizing them as building blocks for the required tissue architectures. A simple 3D printed PLA mould having the...
Tissue engineering faces a major challenge in providing novel, functional materials that will meet the requirements of tissue engineering. These properties can be provided by tricalcium phosphate-based bioceramics (TCP). The combination of a ceramic matrix with polymers creates great opportunities to improve the physicochemical and biological properties of the obtained composites....
The quality of life of millions of patients has been improved by the development materials for regenerative medicine such as total knee joint prostheses, cardiovascular stents, orthopaedic implants, as well scaffolds for tissues regenerative. The global regenerative medicine market size is expected to reach USD 57.08 billion by 2027, growing at a CAGR of 11.27% over the forecast period.
In...
Chitosan is a well-known polymer widely used in tissue engineering and regenerative medicine. It is biocompatible, biodegradable, non-toxic, has antibacterial and osteoconductive properties. It is perfect for the production of implantable materials, including porous scaffolds. Unfortunately, as with most natural polymers, chitosan structures exhibit poor mechanical properties, low durability,...
Injured neural tissue after the intracerebral hemorrhage (ICH) stroke has limited endogenous regeneration because of inflammation and cell apoptosis. The brain cavity and neural scar tissue caused by the hematoma often lead to a permanent behavior disability. Biomaterials can serve as temporary supporting matrices and promote brain tissue regeneration. A chitosan-based self-healing hydrogel...
Introduction:
The surgical repair of nerve transection injuries remains a challenging task and often results in unsatisfactory functional recovery. If a direct coaptation is not possible, the current gold-standard is the use of an autograft. However, the availability of autologous nerve tissue is limited and the harvest of a donor nerve entails functional loss and possible donor site...
Introduction
The rapid integration in the bone tissue and the prevention of bacterial infection are key for the success of the implant. In this regard, a silver (Ag) doped thermochemical treatment that generates an Ag-doped calcium titanate layer on titanium (Ti) surface was previously developed by our group in order to improve the bone-bonding ability and provide antibacterial activity 1....
Functional 3D tissue models are a potentially valuable tool to provide more transferable test results regarding basic research, drug development or other applications than classic 2D cell culture. The biggest bottleneck in the generation of functional 3D tissue models is the incorporation of a reproducible and perfusable vascularization, which on the one side mimics the in vivo hierarchy...
Introduction
Gravity is one of the four fundamental forces that govern the universe and that we experience in daily life without realizing it.
The absence of mechano-stimulation caused by the lack or reduced presence of gravity (microgravity) has been widely studied since the beginning of the space age. This condition creates various cascade reactions in human, resulting in a profound...
Recent regenerative medicine is highly focused on therapies that can effectively treat intravertebral disc (IVD) degeneration. Because of its high efficiency, tissue engineering is a promising alternative therapy for cartilage defects and IVD is one of its main targets. Here we report on the fabrication of injectable electrospun microscaffolds (MS) containing a small chondrogenic agent:...
Derivation of Hepatocytes from stem cells have been established through various protocols including growth factors (GF) and small molecules (SM) among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of cocktail of growth factors and also requires long duration for differentiation, thus limiting its potential clinical applications....
There is a current concept of minimal invasive treatment strategies. A thermoresponsive injectable bone substitute can be moulded into the irregular shape of a bone cavity and can get hardened after application, thus limiting the requirements of complicated surgeries. The injectable bone substitute provides an alternative treatment for those patients who require hard tissue regeneration when...
Introduction:
Modular tissue engineering exploits the 3D self-assembly of cells and building blocks to create larger tissue constructs with higher complexity and resolution.[1] However, current modular tissue engineering strategies have near-exclusively relied on static, non-responsive, micromaterials,[2] whereas functionality of native tissues is dictated by their inherently dynamic...
"Introduction:
Recovery after tendon injuries remains a challenge for the orthopaedics to be solved due to the frequently poor clinical outcomes (1,2). To date, the cellular implications as well as the structural changes in tendinopathy are not fully known, especially concerning the link between inflammation and the early stages of tendinopathy (3). The aim of this research was to assess the...
INTRODUCTION: The question of efficient preservation of cells, especially Mesenchymal stem cells (MSC) becomes more and more urgent due to the impetuous development of cell therapy in clinics. There are two main problems in the improvement of mixtures used for cells cryopreservation. First is the application of DMSO as cryoprotectant, which is known to cause different side effects, and the...
"
Cell-based tissue engineering is promising to create living functional tissue. The implanted cellular construct should be evenly distributed cells in the scaffold, maintain high cellular viability as well as mechanical properties in order to actively participate in the regenerative process. Cell-laden filament-like hydrogels have advantageous for tissue engineering and regeneration...
Introduction
Tissue engineering entails the combination of mechanical, chemical and biological components to process materials that can be engineered towards artificial tissue structures in order to mimic the natural microenvironment of cells; the extracellular matrix (ECM), which provides cells with structural support as well as biochemical, biophysical, and mechanical cues. Biomaterials...
Introduction
Mesenchymal stem cells (MSCs) are widely used in the fields of cell therapy and tissue engineering, due to their wide spectrum of differentiation potential, immunomodulation function and ongoing oxidative stress (OS) reduction. OS impact is often overlooked in these research fields, even though, it is not only responsible for the induction and development of many ailments, e.g.,...
INTRODUCTION
Idiopathic pulmonary fibrosis (IPF) is a lung disease characterized by excessive remodelling of the extracellular matrix (ECM), where fibroblasts are one of the main producers of ECM components. Our aim is to understand how lung fibroblasts respond to mechanical cues in a healthy or diseased ECM composition. We have created an ex vivo model to mechanically stimulate fibroblasts...
INTRODUCTION: There is a growing interest in biomimetic materials which are capable of recapitulating the native extra-cellular environment and drive/guide cell behaviour. Hyaluronan (HA) and fibrin (FB) are two natural extracellular components that each play a pivotal role in modulating cellular behaviour, such as proliferation, migration and differentiation. Cells are capable of sensing...
Heart valve diseases have become one of the main causes for mortality worldwide. To increase the life expectancy of these patients, surgical replacements using mechanical or biological heart valve implants are most commonly used. However, mechanical implants entail the lifelong intake of anticoagulation medication and biological implants exhibit a limited lifetime of 10-20 years. In addition,...
"Introduction
As one of the most outstanding technology, cardiac patches hold the potential to restore cardiac function clinically. Many biomaterials used to fabricate cardiac patches have emerged during the last decade. Synthetic polymers can be tailored on a molecular level to fit any requirement that should be met to function as an integral part of a beating heart.
A facile method was...
One of the biggest challenges in the field of tumour engineering is providing cells with a proper environment mimicking physiological conditions of cancer from the biomechanical point of view. Hard tissue cancers, such as osteosarcoma, are no exception, especially taking into account the complexity of the bone microenvironment. The golden standard is the use of human-derived tissue-engineered...
Introduction: Living tissue is a very complex biological construct made of cells, signaling molecules and multiple extracellular matrix (ECM) components. Each of these elements is equally important to keep the homeostatic balance of tissue and to control the functions of organs. This heterogeneity of living tissues makes their engineering in laboratory conditions challenging 1. Biocompatible...
The lack of bioactivity of poly(N-isopropylacrylamide) (PNIPAM) restricts the use in cell-containing systems to the support as thermoresponsive adhesive substratum with no effect on cell differentiation. In this study, layer-by-layer assembly of polyelectrolytes, allows the combination of PNIPAM-grafted-chitosan (PNIPAM-Chi) with bioactive heparin (Hep) to fabricate PNIPAM−modified...
Introduction:
Medication-related osteonecrosis of the jaw (MRONJ) is an adverse effect of bisphosphonate therapy which is characterised by the loss of overlying soft tissue and exposure of necrotic bone in the oral cavity1, affecting the quality of life of patients2. The lack of effective treatment approaches3 leads to the development of alternative therapies including platelet-rich fibrin...
Introduction
The atrioventricular block constitutes a common congenital disease among pediatric patients. Nowadays the treatment requires repetitive operations for the placement and replacement of technical pacemakers influencing the life quality of young children. In our project, we developed a tissue engineered solution with the aim to avoid the technical pacemakers and therefore the...
Keloids are abnormal scar tissue characterized by excessive proliferation of fibroblast and overabundance of collagen. The keloids often occur on earlobes, shoulders, back of the neck and the chest. To date, the therapeutic treatment of hypertrophic scar includes corticosteroid injection, laser therapy, cryotherapy, radiotherapy, and surgical scar revision. However, none of the above methods...
Holoclone-, meroclone- and paraclone-like colonies were identified in in vitro cultures of normal epithelial cells. In the present study we tested whether cytokeratin 14 (ck14) and sonic hedgehog (shh) expression profiles are correlated with three buccal epithelial clone types. Buccal epithelial cells were isolated from porcine buccal tissues obtained from 9 donors. Cells were seeded into...
Introduction: The enhancement of mesenchymal stem cells (MSC) therapeutic potential is considered an important scientific task. Though it was demonstrated, that pre-conditioning with interferon-γ (IFNγ) is able to enhance the MSC immunomodulatory properties, no current data is known from literature about the effects of interferon-α (IFNα) on MSC. The aim of the present study was to evaluate...
Introduction: As a tissue engineering approach, synthetic and natural polymer composites are explored to create tissue scaffolds that provide requirements such as biocompatibility, biomimetic interface, mechanical properties close to native tissue, and promotion of cell attachment and differentiation. Blends of natural and synthetic electrospun fibers can provide excellent combinations to...
"Introduction: Spinal cord injury (SCI) is a condition that has caused disability worldwide. However, progress in the development of effective therapies to treat SCI-associated neuropathologies has been slow so far. In particular, a few days after injury, a scar made of two components, an outer glial scar and an inner fibrotic scar composed of extracellular matrix (ECM) proteins, is formed and...
"Introduction: The brain organoids derived from human-induced Pluripotent Stem Cells (iPSC) provide a tool to model and study human brain development and its pathology. Up to date reports regarding the role of mitochondrial biogenesis (MB) in cell-type specification during in vitro human cortical development are not available. By inducing mitochondrial biogenesis at different developmental...
The usage of artificial materials for tissue engineering is well-known. Their use as a vascular prosthesis is being considered more often. One of the most promising materials for use for applications in the cardiovascular system is polyurethane which has a good bio- and hemocompatibility as well as appropriate mechanical properties. However, researchers are still looking for methods to improve...
INTRODUCTION
The inorganic phase of bone contains various bioinorganic compounds, apart from calcium, phosphate and carbonate, such as zinc, copper, magnesium, sodium, strontium and many others. These elements have been shown to affect bone mineral features, such as crystallinity, mechanical properties, and degradation. Among these compounds, zinc is an essential element of various enzymes...
"Marine-based novel biomolecules are an emerging set of metabolites for the development of next-generation biomaterials, drugs, and pharmaceutical in vitro platforms [1]. Marine-derived drugs have the potential capacity against different sorts of cancers and isolation of marine-derived natural products has been in the center of attention in developing anticancer drugs because of their strong...
Introduction
Cardiovascular disease (CVD) is a general term for a group of disorders of the heart and blood vessels. According to statistical data of World Health Organization (WHO), CVD is one of the most prevalent disease and the leading cause of death globally in recent years. Therefore, it is justified to search for new, effective therapeutic methods such as stem cell therapy and tissue...
Introduction:
One of the most common labor disturbances is the reduction of prenatal blood flow which results in reduction of oxygen level in neonatal brain. This in turn can lead in long term to the development of drug-resistant epilepsy. Main therapy in the case of epilepsy is administration of sedative drugs which alleviate degree of seizures but also decline the child’s cognitive...
INTRODUCTION
The meniscus is vital for biomechanical and anatomical purposes in the knee, which is frequently injured. Among the diverse biomaterials used for 3D-bioprinting in meniscus regeneration research, silk fibroin (SF) derived from mulberry Bombyx mori (BM) silkworm is extensively studied. Its main drawbacks are the challenge to print it without another material and its lack of the...
The term "cellular senescence" refers to an irreversible cell cycle arrest that can be caused by a variety of stressors and is accompanied by an accumulation of damage, changes in cell shape and secretory profile, and epigenetic abnormalities in primary cells. There is an accumulation of senescent cells in development, aging and tissue regeneration; all of which are conditions with increased...
Introduction:
Petridish-based 2-dimensional (2D) cell culture models are currently used as the first step to test the efficacy of anticancer drugs, but they don’t accurately mimic tumor biology and microenvironment. Moving to 3D models, one of the major concerns is how to assess the drug efficacy. Cell viability is an essential parameter to be monitored to measure cell growth and to assess...
"Introduction
Non-small cell lung cancer (NSCLC) is a widespread tumor classified in heterogeneous subtypes according to the cell of origin and molecular features (1). Disease progression is linked to complex microenvironment, which includes several cell types, matrix components (2) and pervasive angiogenesis (3). Traditional 2D culture fails at resuming the complexity of in-vivo model,...
Chronic rotator cuff tears (RCTs) are one of the most common injuries of shoulder pain. Despite the recent advances in surgical techniques and improved clinical outcomes of arthroscopically repaired rotator cuffs (RCs), complete functional recovery—without retear—of the RC tendon through tendon-to-bone interface (TBI) regeneration remains a key clinical goal to be achieved. Inspired by the...
"INTRODUCTION: Regenerating large tissues requires an intimate supply of the host vascular network, a slow process leading to low viability of the regenerating cells. A solution to this obstacle is the generation of prevascularized tissue engineered constructs. Since Endothelial (ECs) and Mural (MCs) cells, such as smooth muscle cells (SMCs), and pericytes (PCs), are the cellular components of...
Introduction: The cornea which is avascular and transparent tissue is the outer layer of the eye, accepting optical stimuli, and transferring electrochemical signals to the brain. Moreover, the cornea performed a key role in physical barriers against external risks. However, the tissue can be easily damaged and get the disease due to anatomical location. To test irritancy harmful chemicals,...
INTRODUCTION: Light-assisted additive bio-manufacturing has emerged as a powerful tool for custom fabrication of structurally complex 3D tissue models from stem cells.[1-2] Existing in vitro bone models, however, often lack terminally differentiated bone cells named osteocytes which are crucial for bone homeostasis and functional adaptation in response to mechanical loads. Here, we report...
"Introduction. Photodynamic therapy (PDT), an anti-cancer therapeutic approach based on the selective activation by light of photosensitive molecules called ""photosensitizers"" 1, is promising in the context of bladder cancer treatment. This is due to the accessibility of the tumors in the bladder cavity for both instillation of photosensitizer and light irradiation 2. A main drawback of...
There is a growing interest in fabrication of bioinks which on one hand biocompatible and on the other hand possess mechanical properties which would allow to fabricate stable constructs capable to survive for a long time after transplantation. Although choosing appropriate material is essential for bioprinting, there is however, another, equally important issue extensively studied nowadays –...
Alzheimer disease (AD) is the most common cause of dementia and constitutes a major socioeconomic burden. As the underlying cause of AD remains unknown, the clinical need for disease modifying therapies is ever more pressing. Due to the low turnover of neural tissues and the extensive neurodegeneration associated with AD, regenerative medicine therapies are a promising strategy for the...
Chronic kidney diseases (CKD) is the twelfth leading cause of death worldwide, where patients present a gradual loss/impairment in kidney function, leading to end-stage renal disease (ESD). People suffering from ESD have limited life-saving temporal renal replacements options, such as the kidney dialysis, while donor organ transplantation is still the current gold standard, generally hampered...
There are currently over 1.85 million breast implants performed per annum globally at a total value of $2.76 billion with the NHS alone spending £52.5 million. Over 400,000 women per annum need to undergo invasive breast removal surgery due to cancer and suffer tissue loss. Synthetic breast reconstruction, often done at the same time, can also pose significant issues such as scarring and...
Generally, articular cartilage disorder at the junction mainly results from constantly repeated dynamic tension/compression effects with aging time. Piezoelectric materials can deliver variable electric signals analogous to native tissues such as bone and cartilage associated with extracellular matrix (ECM) materials. Thus, there is a high need of degradable piezoelectric scaffold, which...
"Introduction: Promoting and stabilizing microvascularization in engineered tissues and organs is still challenging for the available bioengineering technologies. Extracellular matrix (ECM)-based hydrogels have been extensively employed in microvascularization strategies thanks to their soft mechanics and native-like structure. Nonetheless, their bioactivity and physico-mechanical properties...
Despite key limitations such as host bone supply and quality, donor site morbidity, and immunogenicity, autologous and allograft bone are still considered the clinical standard of care for bone repair [1]. In addition, biomaterials for bone regeneration should be not only biocompatible and osteoconductive, but also osteoinductive [1, 2]. Developing a biomaterial that comprises all the key...
Introduction
Currently, human skin equivalents (HSEs), used as 3D in vitro models, are a particularly attractive intermediate step between conventional cultures and in vivo experimentation. Our group is focused on the development of non-viral gene therapies, based on hyperbranched poly (β-amino esters) (HPAEs), for Recessive Dystrophic Epidermolysis Bullosa (RDEB). Traditionally, RDEB-HSEs...
We have studied synthesis and properties of ultrathin hydrogel coatings with a synthetic extracellular matrix (ECM) analogue: a chimeric peptide comprising a collagen-like peptide block Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- and the fibronectin RGD block -Arg-Gly-Asp-Ser-Pro-Gly (hereafter CLP-RGD) [1]. For ultrathin hydrogel functionalized with the peptide, we employed...
"Introduction
Wound healing is a complex process that involves numerous cell types, cytokines, chemokines, growth factors and extracellular matrix (ECM) components, which work synergistically to achieve healing1,2. When the healing process fails to proceed through the four physiological phases, the wound is referred to as a chronic wound1,2,4,5. Chronic wounds are a significant global...
As the global elderly population increases year by year, the demand for dental implants also increases significantly, Titanium (Ti) is widely used in dental implants due to its good mechanical properties, biocompatibility and corrosion resistance. However, titanium implant surfaces are biologically inert, it won’t react with cells actively and the implant may failed. The success of dental...
Introduction:
Bladder cancer is the 10th most common cancer worldwide. About 20% of bladder cancers are muscle-invasive and are indication for a radical cystectomy. The use of ileal segment is a standard method for urinary diversion after bladder removal. Use of this method extend surgical procedure and lead to numerous metabolic complications. To overcome these side effects, tissue...
The generation of human induced pluripotent stem cell (hiPSC)-derived kidney organoids have facilitated novel insights into renal developmental processes and have the potential to provide personalised treatment strategies for patients with end-stage renal disease. Traditional protocols for the directed differentiation of hiPSC-derived kidney organoids have predominantly focused on biochemical...
Introduction
Bone grafting is among the most frequent forms of transplantation, utilized to manage a variety of bone defect cases. Enriching synthetic bone substitutes with immune-interacting properties can be a strategy to improve their performance. The host’s response to e.g. microbial components can result in both a positive or negative effect on bone formation. As an immunomodulatory...
In vitro models of biological barriers (e.g., lung epithelium, intestinal epithelium) provide an important benchmark for studying the physiopathological processes (e.g., nutrient and metabolite exchange, interactions with external virus or bacteria) involved in the development of several diseases (e.g., respiratory tract infections, carcinomas). These models represent a reliable platform for a...
"Introduction
Anatomically-correct models of human skin are highly desired by both biomedical sciences and industry. Organotypic skin cultures, termed full-thickness skin equivalents, including fibroblasts and keratinocytes, thus forming dermis and epidermis are in use. However, a more detailed model of the skin is difficult to set up due to its cellular heterogeneity, complex vascular...
INTRODUCTION
Bioprinting is gaining an ever-increasing research interest thanks to its promising new applications in the field of tissue engineering. The main issue regarding this biofabrication technique is the engineering of suitable bioinks, accommodating both the requirements for fabrication and for cell culture and signalling. Versatile platform bioinks, with easily tailorable...
"Burned skin wound treatment is one of the most expensive burdens on healthcare systems worldwide. The severity and extension of burn trauma could elevate the rate of hospitalization, and patients with burn wounds are especially vulnerable to infections. Burn injuries are very challenging to manage since it causes loss of the integrity of large portions of the skin, leading to major disability...
