Recombinant expression of human type 1 collagen for tissue engineering and biomaterials

This $863,697 Project Grant from the National Institutes of Health's National Institute of General Medical Sciences will support Provenance Group Inc.'s efforts to efficiently synthesize full-length human Type I collagen with appropriate post-translational modifications at high yields. The company will demonstrate that the recombinant collagen resembles its native counterpart and generate highly productive strains expressing full-length human Type I collagen showing appropriate prolyl hydroxylation. Provenance Group will optimize production processes at different scales from shake flasks to bioreactors. This work aims to establish a cost-effective production strategy for recombinant human Type I collagen to address limitations in its availability for tissue engineering and biomaterials applications. If successful, it could open avenues for tailoring collagen properties and developing novel therapeutic and biomedical uses. The funding falls under the Biomedical Research and Research Training program (CFDA 93.859), which supports basic research increasing understanding of biological processes and laying foundations for advances in disease diagnosis, treatment and prevention.

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.