Many reported hydrogels used in tissue engineering applications are fabricated from synthetic copolymers or cross-linked polymer composites, such as polyactide-poly(ethylene glycol), polyurethane-poly(ethylene oxide), and polylactide-co-glycolic acid-poly(ethylene glycol). Such printable scaffolds need to have either reversible sol-gel properties or rapid gelation times. In addition, when designing implantable materials for surgical applications such as osteochondral lesion repair, 5 the scaffolds should be compatible with modern surgical techniques like arthroscopy or bioprinting. Functional scaffolds for regenerative medical applications should possess a number of properties: they should have biophysical and mechanical properties that mimic the microenvironment of healthy tissue (typically the extracellular matrix) they should be a 3D porous network that promotes cell growth by allowing the transport of nutrients and metabolic waste in and out of the scaffold and they should have tunable biodegradability allowing the rate of scaffold degradation to match that of new tissue growth. 4 As such, there is an urgent need to develop implantable scaffolds to encapsulate cells and prevent their migration away from damaged tissue at the same time promoting the viability and the regeneration of the healthy cells, tissues, or organs. For example, Geng found that over 99% of mesenchymal stem cells injected into a mouse were nonfunctional after just 4 days. One significant reason for this is that the majority of transplanted stem cells quickly become nonfunctional after transplantation due to migration away from the damaged tissues or organs, loss of differentiation capability, and cell death. 3ĭespite their promise, progress in stem cell tissue engineering has been slow, and there have been few examples of successful clinical translation. Furthermore, many adult stem cells, particularly mesenchymal stem cells, have anti-inflammatory and anti-immunomodulatory properties which can further encourage healthy tissue regeneration. Transplanted stem cells experience cues from their in vivo microenvironment encouraging them to differentiate and regenerate damaged tissues and organs. Once harvested, the cells are expanded in vitro and transplanted into the affected region of the body. Harvesting can be either from the patient (autologous) or from a donor (allogenic). 2 These adult stem cells avoid the ethical concerns surrounding embryonic stem cells and can be harvested from healthy donor tissue. 1 Significant research has taken place investigating the applications of mesenchymal, hematopoietic, or neuronal stem cells in regenerative medicine. Therapies involving stem cell transplantation have the potential to revolutionize the treatment of some of the most socioeconomically devastating diseases and traumas in the world today including osteoarthritis, cardiac disease, stroke, Alzheimer's disease, the treatment of severe burns, and a range of cancers. Finally, the author outlines a selection of studies that elucidate molecular assembly mechanisms and biophysical properties of amyloid-like peptide nanofibrils and suggests how studies like these might lead to the ability to generate nanofibril scaffolds with bespoke properties for tissue engineering. The author also presents some fundamental knowledge gaps which are preventing the widespread translation of such scaffolds. The author highlights recent studies which have shown that these scaffolds can be used to promote cell and tissue regeneration both in vitro and in vivo. In this review, the author highlights a selection of important proof-of-principle papers that show how this class of self-assembled networks is highly suited to biomaterial scaffold development. Networks of amyloid-like nanofibrils assembled from short peptide sequences have the ability to form scaffolds that can encapsulate clinically relevant stem cells encouraging their attachment, growth, and differentiation into various lineages which can be used in tissue engineering applications to treat a range of diseases and traumas.
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