In the development of tissue engineering strategies to replace, remodel, regenerate, or support damaged tissue, the development of bioinspired biomaterials that recapitulate the physicochemical characteristics of the extracellular matrix has received increased attention. Given the compositional heterogeneity and tissue-to-tissue variation of the extracellular matrix, the design, choice of polymer, crosslinking, and nature of the resulting biomaterials are normally depended on intended application. Generally, these biomaterials are usually made of degradable or nondegradable biomaterials that can be used as cell or drug carriers. In recent years, efforts to endow reciprocal biomaterial-cell interaction properties in scaffolds have inspired controlled synthesis, derivatization, and functionalization of the polymers used. In this regard, elastin-like recombinant proteins have generated interest and continue to be developed further owing to their modular design at a molecular level. In this review, the authors provide a summary of key extracellular matrix features relevant to biomaterials design and discuss current approaches in the development of extracellular matrix-inspired elastin-like recombinant protein based biomaterials.
The growing number of patients requiring liver transplantation for chronic liver disease cannot be currently met due to a shortage in donor tissue. As such, alternative tissue engineering approaches combining the use of acellular biological scaffolds and different cell populations (hepatic or progenitor) are being explored to augment the demand for functional organs. Our goal was to produce a clinically relevant sized scaffold from a sustainable source within 24 hours, whilst preserving the extra cellular matrix (ECM) to facilitate cell repopulation at a later stage. Whole porcine livers underwent perfusion de-cellularisation via the hepatic artery and hepatic portal vein using a combination of saponin, sodium deoxycholate (SOC) and deionised water washes resulting in an acellular scaffold with an intact vasculature and preserved ECM. Molecular and immuno-histochemical analysis (collagen I and IV and laminin) showed complete removal of any DNA material, together with excellent retention of glycosaminoglycans and collagen. FTIR analysis showed both absence of nuclear material and removal of any detergent residue, which was successfully achieved after additional ethanol gradient washes.Samples of the de-cellularised scaffold were assessed for cytotoxicity by seeding with porcine adipose derived mesenchymal stem cells in vitro, these cells over a 10 day period showed attachment and proliferation. Perfusion of the vascular tree with contrast media followed by CT imaging showed an intact vascular network. In vivo implantation of whole intact non-seeded livers, into a porcine model (as auxiliary graft) showed uniform perfusion macroscopically and histologically. Using this method, it is possible to create an acellular, clinically sized, liver scaffold with intact vasculature in less than 24 hours.
Porous biomaterials are of significant interest in a variety of biomedical applications as they enable the diffusion of nutrients and gases as well as the removal of metabolic waste from implants. Pores also provide 3D spaces for cell compartmentalization and the development of complex structures such as vasculature and the extracellular matrix. Given the variation in the extracellular matrix composition across and within different tissues, it is necessary to tailor the physicochemical characteristics of biomaterials and or surfaces thereof for optimal bespoke applications. In this regard, different synthetic and natural polymers have seen increased usage in the development of biomaterials and surface coatings; among them, elastin-like polypeptides and their recombinant derivatives have received increased advocacy. The modular assembly of these molecules, which can be controlled at a molecular level, presents a flexible platform for the endowment of bespoke biomaterial properties. In this review, various elastin-like recombinamer–based porous biomaterials for both soft and hard tissue applications are discussed and their current and future applications evaluated.
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