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...
"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...