Spatiotemporally Controlled Keratin Biomaterial Delivery System for Functional Tissue Regeneration Phase II

Skeletal muscle injury is a significant challenge to warfighters due to the severity of the injuries often caused by Improvised Explosive Devices. Currently, there are few viable clinical treatment options for these types of injuries. Keratin hydrogels offer a solution to these challenges as carriers of cells and growth factors. Human epithelial keratins are the major structural proteins in cells and form a cytoplasmic network of intermediate filaments. Human hair keratins are genetically similar to epithelial keratins and their intrinsic characteristics make them unique candidates for biomaterial-based carriers of growth factors and cells. In the Phase I project, we showed that keratin hydrogels provide sustained release of growth factors and maintain cell viability in vivo. This Phase II proposal will build on these findings and move toward a product that facilitates skeletal muscle regeneration. The Phase II objectives are to optimize formulations of keratin for delivery of cells and supporting growth factors (FGF and IGF-1), to test the safety and immunogenicity of these formulations, and to assess the functional muscle recovery in two rodent models of muscle loss. Completion of the Phase II objectives will yield a keratin hydrogel formulation optimized for in vivo regeneration of injured skeletal muscle.