Fabrication of 3D Cardiac Patches for Myocardial Recovery

描述(申请人提供)：心血管疾病在美国影响着8000万人，是导致死亡的主要原因。当前治疗方法的重大局限性要求开发新的策略。心血管组织工程是一个新兴的领域，致力于开发生物替代品来恢复、维持或改善组织功能。生物工程三维(3D)心脏补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。本研究的重点是构建三维心肌，利用受控拉伸来支持组织发育，并测试心脏补片增强梗死心肌功能的能力。拟议的研究分为三个部分。本研究的第一部分集中于定义细胞培养条件，以最大限度地发挥3D心脏补片的功能性能。第二部分集中于开发给3D心脏补片提供受控拉伸的方案，以进一步提高心脏补片的功能性能。在该项目的第三部分，利用优化的细胞培养条件构建的心脏补片将被植入梗死心脏的表面。心脏补片增强衰竭心肌功能的能力将作为损伤后时间和补片植入时间的函数进行研究。这项研究的成功完成将导致3D心脏补片的开发，这种补片的功能将更接近正常哺乳动物的心肌，还将为心脏补片在支持衰竭心肌功能恢复方面的潜在适用性提供洞察。 公共卫生相关性：心血管疾病仍然是一个重大的医学挑战，迫切需要开发新的治疗方案。在这项研究中，将制作心脏补片并进行测试，作为支持受损心脏恢复的平台。这项研究的成功完成将导致平台技术的发展，并为心力衰竭患者提供一种新的治疗模式，使全球数百万患者受益。

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.