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

NIH RePORTER · NIH · R43 · $287,899 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
10325908
Project number
1R43GM144011-01
Recipient
PROVENANCE GROUP, INC.
Principal Investigator
Genevieve M. Vidanes
Activity code
R43
Funding institute
NIH
Fiscal year
2021
Award amount
$287,899
Award type
1
Project period
2021-09-01 → 2023-08-31