ORIGIN OF CELLS THAT REPOPULATE RESORBABLE ECM SCAFFOLDS

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This application is in response to Program Announcement 99-024: Research on Tissue Engineering. The overall goal of our tissue engineering efforts is to develop safe and effective scaffolds that support the restoration of injured or damaged tissues. Specifically, the proposed research will investigate the interaction between acellular, resorbable scaffold/matrices and the cells which repopulate such scaffolds following implantation in mammalian hosts. The central hypothesis of this application is that scaffolds developed from naturally-occurring extracellular matrix (ECM) can recruit circulating progenitor cells which inhabit the scaffold, proliferate, and differentiate into site-specific functional tissues. Two controlled animal studies are proposed; each of which uses two separate mouse models that allow for selective identification of cells which originate in the bone marrow. These studies are designed to successfully accomplish three specific aims: (1) to determine the contribution of circulating progenitor cells to remodeled tissue when naturally-occurring ECMs are used as resorbable scaffolds for tissue repair; (2) to determine the source of endothelial cells which participate in neovascularization of ECM scaffolds; and (3) to determine the effect of adding ECM materials to porous synthetic polymer scaffolds upon neovascularization and the source of endothelial cells which contribute to remodeling. The origin (source) of cells which participate in ECM scaffold remodeling will be compared against the origin of cells which contribute to the remodeling of other acellular resorbable scaffolds; specifically Type I collagen, Alloderm , and poly(L- glycolic acid) (PLGA). Completion of these 3 specific aims will provide important and necessary information for the future intelligent design of scaffolds in a variety of tissue engineering applications; especially those applications where neovascularization is a critical determinant for success. The rationale for the proposed research is based upon extensive preliminary studies, recent findings in progenitor cell biology, an innovative animal model developed by one of the co- investigators, and will be conducted by an experienced interdisciplinary research team in a timely fashion.