Fabrication of 3D Cardiac Patches for Myocardial Recovery

描述（由申请人提供）：心血管疾病影响着美国8000万人，是导致死亡的主要原因。当前治疗的显著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，其重点是发展生物替代品来恢复、维持或改善组织功能。生物工程三维心脏贴片可以在临床上用于心肌梗死部位，促进左心室收缩功能的增强。本研究的重点是3D心肌的制造，使用控制拉伸来支持组织发育，并测试心脏贴片增强梗死心肌功能的能力。拟议的研究分为三个部分。本研究的第一部分侧重于确定细胞培养条件，以最大限度地提高3D心脏贴片的功能性能。第二部分的重点是开发方案，以提供可控制的拉伸到3D心脏贴片，以进一步提高心脏贴片的功能性能。在本项目的第三部分，使用优化的细胞培养条件和拉伸条件制造的心脏贴片将被植入梗死心脏表面。心脏贴片增强衰竭心肌功能的能力将被研究，作为损伤后时间和贴片植入时间的函数。这项研究的成功完成将导致3D心脏贴片的发展，它将更接近正常哺乳动物心肌的功能，也将为心脏贴片在支持衰竭心肌功能恢复方面的潜在适用性提供见解。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Cardiovascular disorders remain a major medical challenge with an urgent need to develop novel therapeutic options. In this study, cardiac patches will be fabricated and tested as a platform to support the recovery of infracted hearts. Successful completion of this study will result in the development of platform technology and provide a novel treatment modality for heart failure patients, benefiting millions of patients around the world.