Cell Adhesion and Guidance Motifs for Cardiac Grafts

描述（由申请人提供）：本项目的长期目标是开发一种组织工程心脏移植物（TECG），用于先天性和获得性心脏病变的手术修复。本文提出的研究的终点目标是开发在心肌梗塞（MI）的体内大鼠模型中引起可证实的机械益处的结构良好组织的和机电功能的TECG。这一终点目标将通过首先量化蛋白质修饰的聚（癸二酸甘油酯）（PGS）弹性体支架的功效来实现，该支架表现出细胞定向的3-D开孔结构（细胞引导基序; CGM），以促进心肌细胞（CM）粘附、存活和对齐。其次，将评估体外双轴机械刺激在促进适于植入的机电功能TECG的组织化方面的功效。具体目标是：1.具有细胞引导基序（CGM）的微制造弹性支架。2.量化CM粘附、存活和在蛋白质修饰的CGM-PGS支架上的对齐。3.量化TECG响应于体外双轴拉伸的机电功能。4.心肌梗塞（MI）啮齿动物模型中TECG的体内研究。

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop a tissue engineered cardiac graft (TECG) for use in the surgical repair of congenital and acquired lesions of the heart. The end-point objective of the research proposed herein is to develop a structurally well-organized and electromechanically functional TECG eliciting demonstrable mechanical benefits in an in vivo rat model of myocardial infarction (Ml). This end-point objective will be approached by first quantifying the efficacy of protein-modified, poly(glycerol sebacate) (PGS) elastomeric scaffolds exhibiting cell-orienting 3-D open pore structures (cellular guidance motifs; CGM) to promote cardiomyocyte (CM) adhesion, survival, and alignment. Secondly, the efficacy of in vitro biaxial mechanical stimulation in promoting the organization of electromechanically functional TECG suitable for implantation will be assessed. The specific aims are: 1. Microfabricate elastomeric scaffolds with cellular guidance motifs (CGM). 2. Quantify CM adhesion, survival, and alignment on protein-modified CGM-PGS scaffolds. 3. Quantify TECG electromechanical function in response to in vitro biaxial stretch. 4. In vivo studies of TECG in a rodent model of myocardial infarction (Ml).