Fabrication of 3D Cardiac Patches for Myocardial Recovery

项目概要/摘要 心血管疾病影响美国8000万人，是死亡的主要原因。 当前治疗方法的重大局限性需要开发新的策略。心血管 组织工程是一个新兴的领域，其重点是开发生物替代物以恢复， 维持或改善组织功能。可以利用生物工程三维（3D）心脏贴片 临床上在心肌梗塞部位，促进左心室收缩功能的增加。这 这项研究的重点是制造3D心肌，使用受控拉伸来支持组织发育 以及测试心脏补片增强梗塞心肌功能的能力。 拟议的研究分为三个部分。本研究的第一部分主要是界定 细胞培养条件以最大化3D心脏补片的功能性能。第二部分是 专注于开发协议，为3D心脏贴片提供受控拉伸，以进一步 增加心脏补片的功能性能。在这个项目的第三部分， 使用优化的细胞培养条件制造并使用拉伸进行调节，将被植入 梗塞心脏的表面。心脏补片增强功能性能的能力 将研究心肌作为损伤后时间和补片植入时间的函数。 这项研究的成功完成将导致3D心脏贴片的开发， 功能更接近正常哺乳动物心肌，也将提供对潜在适用性的深入了解 心脏补片在支持衰竭心肌功能恢复中的作用。

PROJECT SUMMARY/ABSTRACT Cardiovascular disease affects 80 million people in the US and is the leading cause of death. Significant limitations of current treatments necessitate the development of novel strategies. Cardiovascular tissue engineering is an emerging field focused on the development of biological substitutes to restore, maintain, or improve tissue function. Bioengineered 3-dimensional (3D) cardiac patches can be utilized clinically at the site of a myocardial infarction, promoting increased left ventricular contractile function. This study is focused on the fabrication of 3D heart muscle, using controlled stretch to support tissue development and testing the ability of cardiac patches to augment the function of infarcted myocardium. The proposed study is divided into three components. The first part of this study is focused on defining cell culture conditions to maximize the functional performance of 3D cardiac patches. The second part is focused on developing protocols to deliver controlled stretch to the 3D cardiac patches, in order to further increase the functional performance of cardiac patches. In the third part of this project, cardiac patches fabricated using optimized cell culture conditions and conditioned using stretch, will be implanted on the surface of infarcted hearts. The ability of the cardiac patches to augment the functional performance of failing myocardium will be studied, as a function of post-injury time and patch implantation time. Successful completion of this study will result in the development of 3D cardiac patches which will be functional closer to normal mammalian heart muscle and will also provide insight into the potential applicability of the cardiac patches in supporting functional recovery of failing myocardium.