Cell Adhesion and Guidance Motifs for Cardiac Grafts

心脏移植物的细胞粘附和引导基序

• 批准号: 7231452
• 负责人: GEORGE C ENGELMAYR
• 金额: $ 4.6万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231452
• 关键词: 3-Dimensional; Adhesions; Adhesives; Adsorption; Angiopoietin-1; Biochemical; Biological Assay; Bioreactors; Cardiac Myocytes; Cell Adhesion; Cells; Cellular Structures; Connexin 43; Creatine Kinase; DNA; Devices; Echocardiography; Elastomers; Electromagnetics; End Point; Exhibits; Extracellular Matrix; F-Actin; Fellowship; Heart; Heart Transplantation; Histology; Immunohistochemistry; In Vitro; Incubated; Individual; Label; Laser Scanning Confocal Microscopy; Lesion; Measures; Mechanical Stimulation; Mechanics; Membrane Proteins; Metabolism; Methods; Modeling; Myocardial Infarction; Myosin Heavy Chains; Names; Natural regeneration; Neonatal; Operative Surgical Procedures; Peptides; Process; Property; Proteins; Protocols documentation; Rate; Rattus; Research; Rodent Model; Scanning Electron Microscopy; Standards of Weights and Measures; Stretching; Surface; Surgical sutures; Testing; Time; Tissue Engineering; Troponin; Ventricular Function; Western Blotting; caspase-3; density; design; elastomeric; implantation; improved; in vivo; intercellular communication; left coronary artery; light scattering; lithography; poly(glycerol-sebacate); repaired; response; scaffold

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).

描述（由申请人提供）：该项目的长期目标是开发一种组织工程心脏移植物（TECG），用于先天性和后天性心脏病变的手术修复。本文提出的研究的最终目标是开发一种结构组织良好且具有机电功能的TECG，其在心肌梗塞(M1)的体内大鼠模型中产生明显的机械益处。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这一终点目标，该支架表现出细胞定向 3-D 开孔结构（细胞引导基序；CGM）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合植入的机电功能 TECG 组织方面的功效。具体目标是： 1. 微制造具有细胞引导基序（CGM）的弹性支架。 2. 量化蛋白质修饰的 CGM-PGS 支架上的 CM 粘附、存活和排列。 3. 量化 TECG 响应体外双轴拉伸的机电功能。 4.心肌梗塞(M1)啮齿动物模型中TECG的体内研究。