Recombinant Expression of Human Type 1 Collagen for Tissue Engineering and Biomaterials

Abstract Collagen forms a highly organized, three-dimensional network that facilitates cell attachment, migration, proliferation and differentiation. Strength, persistence and biocompatibility are the inherent properties of collagens that make them well suited as scaffolds in tissue engineering efforts for repair and reconstruction of tissue, bone, and skin. Currently, the primary source of these collagens is animal derived, which causes concerns (reliability, safety, inconsistency, etc). While recombinant production of human collagens promises the most likely solution, the state of art protein production technologies suffer inefficiencies in the production of full length, functional collagens. As such, there’s a recognizable gap between the demand for recombinant collagens and the supply thereof. Provenance has devised a unique strategy for overcoming the limitations of these recombinant protein production systems. We propose to use our novel platform to efficiently synthesize full length human type I collagens with the required post translational modifications at high titers. We will demonstrate the recombinant human type I collagen resembles its native counterpart. We propose to generate highly productive strains expressing full length human type I collagen, that shows the appropriate prolyl hydroxylation, and optimize their production processes at different scales (shake flasks, bioreactors). Ultimately, the approach described here should lead to a cost effective production strategy for recombinant human type I collagen, and alleviate the severe limitations in the availability of this collagen for tissue engineering, and as biomaterials in other biomedical applications. In addition, the availability of an inexpensive source of human type I collagen should allow researchers to expand the role of collagen as a biomaterial for tissue engineering applications. Successful completion of the work proposed in this Phase I proposal can open avenues towards tailoring properties of collagens, a long term goal to impart new functionalities which in turn can lead to novel applications in therapeutic and biomedical applications.Public Health Relevance (also called Project Narrative) There is a significant and urgent need to devise a strategy for procuring recombinant human type I collagen to meet the rising demand for its use as biomaterial in tissue engineering spaces. This proposal aims to establish a methodology to produce fully functional human type I collagen cost effectively. Successful completion of the work proposed in this Phase I SBIR should lay a foundation towards commercial production of human type I collagen at price points that facilitate market adoption into tissue engineering applications more widely than is currently feasible.