Multifunctional tunable elastin-like recombinamer-based hydrogels customized for neovascularisation and dynamic cell niche construction purposes

Abstract

Tissue engineering and regenerative medicine applications require nowadays the development of advanced medical devices, customized for a specific application. The common goal of those used in soft tissue regeneration is to support the neovascularisation of the applied scaffolds to ensure the functionality of newly formed tissue. DNA recombinant technology allows to meet these aims as it has been used to design and synthesize smart materials with strict control over their composition, and consequently, over their physio-chemical features. In this work we applied this recently developed molecular biology tool to produce elastin-like recombinamers (ELRs), synthetic polypeptides inspired in the structure of natural elastin. They have been granted specific bioactivities controlled by intrinsic mechanisms of the body. These characteristics are biodegradability through sensitivity to cleavage by ubiquitously expressed enzymes, pro-angiogenic behaviour thank to an indirect recruitment of growth factors and controlled thermodynamics. The produced ELRs have been either crosslinked by physical interactions or chemically modified in order to form stable covalently-crosslinked hydrogels. The mechanical features, cytocompatibility and efficiency in the context of the bioactivity implemented have been tested. The results are promising. Remarkably, preliminary in vitro cell culture studies and in vivo animal studies have shown the materials do support the desirable neovascularisation and suggest they have a great potential for their future translational path.