NOVEL SCAFFOLDS FOR BLADDER REPAIR

描述（改编自申请人摘要）：目的：开发 用于膀胱修复的生物活性机械响应支架。重要性： 膀胱扩大术是治疗排尿困难的有效方法 由多种病因引起的疾病。所需的材料 促进膀胱重建。假设：移植胶原蛋白衍生的细胞 在可再吸收的聚合物支架上结合肽将促进粘附， 细胞的迁移和分化。背景和以前的工作： 生物材料被制成对细胞是惰性的，以防止不良反应。 然而，许多生物学上无活性的材料引起局部纤维化， 其他炎性反应。以前的工作是基于我们发现的 I型胶原蛋白中有效的非RGD细胞结合结构域表明， 将其合成肽类似物P-15掺入多种底物中 促进细胞粘附、迁移和分化， vivo.具体目的：1）合成可吸收聚酯基质， P-15，2）通过以下方法检查基质的粘附、迁移和定殖： 膀胱平滑肌细胞和成纤维细胞，3）检测 基质大分子4）检查生长因子TGF-β，EGF， PDGF、KGF对集落形成和基质大分子表达的影响。在第二阶段， 基质的性能将在实验中进行体内评价 为人体试验做准备的动物模型。 拟议商业应用：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