NOVEL SCAFFOLDS FOR BLADDER REPAIR

Biomimesys, Inc., San Mateo CA

Investigators

Abstract

DESCRIPTION (Adapted from the Applicant's Abstract): Objective: To develop bioactive, mechanically responsive scaffolds for bladder repair. Significance: Augmentation of bladder is an effective treatment modality for voiding disorders arising from a variety of etiologies. Materials are needed that would facilitate bladder reconstruction. Hypothesis: Grafting a collagen-derived cell binding peptide on a resorbable polymer scaffold will facilitate the adhesion, migration, and differentiation of cells. Background and Previous Work: Biomaterials are made be inert towards cells in order to forestall adverse reaction yet many biologically inactive materials elicit local fibrosis and other sequlae of inflammatory response. Previous work based on our discovery of a potent non-RGD cell binding domain in type I collagen showed that the incorporation of its synthetic peptide analogue P-15 in a variety of substrates promotes cell adhesion, migration, and differentiation both in vitro and in vivo. Specific Aims: 1) To synthesize resorbable polyester matrices containing P-15, 2) Examine the adhesion, migration, and colonization of matrices by urothelium, smooth muscle cells, and fibroblasts, 3) Examine the exprssion of matrix macromolecules 4) Examine the effect of growth factors TGF-beta, EGF, PDGF, KGF on colony formation and matrix macromolecule expression. In Phase II, the performance of the matrices will be evaluated in vivo in experimental animal models in preparation for testing in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE