There is an unquestionable need for improved scaffolds if vascular substitutes are to be produced and used clinically in reparative procedures. Fully biological polymer scaffolds have the advantage that cells are able to recognize and bind to them, and ultimately to remodel and/or replace them with new matrix. The innovative approach used in this project is to combine collagen and fibrin to develop a new class of composite scaffolds that directly address one of the main shortcomings of current biopolymer matrices: the lack of adequate mechanical strength. Our hypothesis is that the combination of collagen and fibrin in a laminate architecture and/or as an interpenetrating double polymer network will provide superior mechanical properties, compared to either material alone. In addition, we hypothesize that the biochemical effects of fibrin on vascular smooth muscle cells (SMC) in these collagen-fibrin constructs will induce cell proliferation and matrix deposition that will further improve construct properties. These hypotheses will be tested by completing the following Specific Aims: 1) Construct and mechanically characterize layered composite and mixed composite structures of collagen and fibrin, and 2) Determine the effect of collagen-fibrin composites on SMC proliferation, matrix synthesis and phenotype-specific protein expression. The concentration, ratio and layering configuration of collagen and fibrin will be used to optimize mechanical properties. In addition, a better understanding of cell-matrix interactions and their effects on SMC function will allow the scaffold composition to be tailored to encourage the development of robust tissues. We will thus characterize the physical and biochemical functionality of the matrices produced, with the objective of combining this information to yield a novel type of fully biological composite material that can withstand the forces of the vascular system, while supporting appropriate cell function and tissue remodeling.
