Cell Adhesion and Guidance Motifs for Cardiac Grafts

描述(申请人提供)：该项目的长期目标是开发一种组织工程心脏移植物，用于先天性和获得性心脏损伤的外科修复。这项研究的最终目的是开发一种结构良好、机电功能良好的TCG，在活体大鼠心肌梗死(ML)模型中获得明显的机械益处。这一终点目标将首先通过量化蛋白质修饰的聚癸二酸甘油(PGS)弹性支架的有效性来实现，该支架具有面向细胞的3-D开放孔结构(细胞引导基序；CGM)，以促进心肌细胞(CM)的黏附、存活和排列。其次，将评估体外双轴机械刺激在促进适合植入的机电功能TCG组织方面的效果。具体目标是：1.微加工细胞导向模体(CGM)弹性支架。2.定量测定CM在蛋白质修饰的CGM-PGS支架上的黏附、存活和排列情况。3.定量测定体外双轴牵张对TCG机电功能的影响。4.大鼠心肌梗死动物模型的TCG活体研究。

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).