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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB003978-02
Application #
6915572
Study Section
Special Emphasis Panel (ZRG1-BMBI (01))
Program Officer
Wang, Fei
Project Start
2004-08-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$173,278
Indirect Cost
Name
Rensselaer Polytechnic Institute
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
002430742
City
Troy
State
NY
Country
United States
Zip Code
12180
Rowe, Shaneen L; Stegemann, Jan P (2009) Microstructure and mechanics of collagen-fibrin matrices polymerized using ancrod snake venom enzyme. J Biomech Eng 131:061012
Hong, Helen; Stegemann, Jan P (2008) 2D and 3D collagen and fibrin biopolymers promote specific ECM and integrin gene expression by vascular smooth muscle cells. J Biomater Sci Polym Ed 19:1279-93
Rowe, Shaneen L; Lee, Sungyun; Stegemann, Jan P (2007) Influence of thrombin concentration on the mechanical and morphological properties of cell-seeded fibrin hydrogels. Acta Biomater 3:59-67
Stegemann, Jan P; Kaszuba, Stephanie N; Rowe, Shaneen L (2007) Review: advances in vascular tissue engineering using protein-based biomaterials. Tissue Eng 13:2601-13
Hong, Helen; McCullough, Caitlyn M; Stegemann, Jan P (2007) The role of ERK signaling in protein hydrogel remodeling by vascular smooth muscle cells. Biomaterials 28:3824-33
Rowe, Shaneen L; Stegemann, Jan P (2006) Interpenetrating collagen-fibrin composite matrices with varying protein contents and ratios. Biomacromolecules 7:2942-8