Speaker
Description
"Introduction
Everyday thousands of people of all ages across the world are admitted to hospitals because of the severe injuries or malfunction of some vital organs [1]. Organ or tissue transplantation is a standard therapy to treat these patients. Irony of fact that many of these people will die due to the paucity of donor organs and high processing cost involved in organ transplantation [2]. To meet this global clinical need, tissue engineering has emerged to regenerate injured or diseased tissues and organs. Biomaterials serve as scaffolds to support cells as well as to guide them towards specific tissue construct [1]. Recently, hydrogels - a crosslinked three-dimensional (3D) polymeric network with elegant ability to mimic extracellular matrix functionalities - have evolved as a potential scaffold for controlling/guiding cell fate towards a specific tissue/organ [3]. However, it is still a critical engineering challenge to design clinically relevant hydrogel scaffolds in a congenial and sustainable approach. Herein, we develop a versatile, customizable, and scalable synthesis protocol of hydrogel scaffolds with physiologically relevant features for therapeutic applications.
Methodology
We successfully developed a green synthesis approach, maintaining an engineering mindset, to formulate a set of gelatin-based multicomponent hybrid hydrogels with 3D porous structural stability, tunable biomimetic mechanical properties, controllable degradability, electrical conductivity, efficient sterilizability, and biocompatibility [4]. The novel eco-friendly hydrogel synthesis protocol successively involved four steps: (i) liquid-phase crosslinking/grafting, (ii) unidirectional freezing, (iii) freeze-drying, and finally (iv) post-curing. Taking advantage of the reactivity of epoxide-end PEG (act as crosslinking agent) with available various functional groups of gelatin in aqueous environment, the crosslinked network of gelatin-PEG was attained, keeping a constant feed ratio of gelatin to PEG for all formulations.
Results
The developed synthesis strategy offered simplicity, versatility, customizability, sterilizability, biocompatibility and scalability - a combo of some important features favoring clinical translation of biomaterials. All hybrid hydrogels showed highly interconnected open porous structures suitable for tissue engineering applications. The hydrogels showed constituent-and concentration-dependent anisotropy. Mechanically, all hydrogels showed robust stability, J-shaped stress-strain curve, excellent shape recoverability, strong fatigue resistance and stress relaxing behavior. Biological experiment with human bone marrow mesenchymal stromal cells revealed that hydrogels were biocompatible, and their compositions and dynamic mechanical properties were suitable to support stem cell proliferation, as well as osteogenic and chondrogenic differentiation. Both variation in compositions and stress relaxation behavior of hydrogels were found to guide stem cells towards different level of matured osteogenesis and stable chondrogenesis.
Conclusion
The developed robust synthesis strategy offers preparation of next generation hydrogel scaffolds with tissue-like mechanics and morphologies, tunable degradation, greater customizability in composition and architecture, and biocompatibility for a wide range of tissue engineering applications, including nerve to bone tissue regeneration.
References
1. Sadtler, K. et al., Nat. Rev. Mater. 1.7, 1-17 (2016).
2. Giwa, S. et al., Nat. Biotechnol. 35.6, 530-542 (2017).
3. Khademhosseini, A. et al., Proc. Natl. Acad. Sci. USA 103.8, 2480-2487 (2006).
4. Dey, K. et al., Macromol. Biosci. 19(8), 2019: 1900099.
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