NOVEL SCAFFOLDS FOR BLADDER REPAIR

描述(改编自申请者摘要)：目标：开发 用于膀胱修复的生物活性、机械响应支架。重要意义： 膀胱扩大术是治疗排尿的有效方法 由各种原因引起的疾病。需要的材料将是 促进膀胱重建。假设：移植胶原蛋白来源的细胞 可吸收聚合物支架上的结合肽将促进粘合， 细胞的迁移和分化。背景和以前的工作： 生物材料对细胞是惰性的，以防止有害的 反应然而许多生物活性物质会引起局部纤维化和 炎症反应的其他序列。之前的工作基于我们发现的 I型胶原中一个有效的非RGD细胞结合域表明， 其合成肽类似物P-15在多种底物上的掺入 在体外和体内促进细胞黏附、迁移和分化 活着。具体目标：1)合成含有以下成分的可吸收聚酯基质 P-15，2)检查基质的黏附、迁移和定植 尿路上皮、平滑肌细胞和成纤维细胞，3)检测 基质大分子4)检测生长因子转化生长因子β、表皮生长因子、 PDGF、KGF对集落形成和基质大分子表达的影响。在第二阶段， 这些基质的性能将在体内进行实验评估 准备在人体上进行试验的动物模型。 建议的商业应用：不可用

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