Restoring LV Function Post-MI Using Fibrin-Gel Based Engineered Myocardium

心血管疾病可导致心肌梗塞（MI）和随后的心力衰竭。有 目前有许多旨在预防或治疗MI后心力衰竭的疗法。只有心 移植替代梗死心肌以恢复心脏功能，但缺乏供体 心脏和心血管疾病的发病率继续上升。一个新的和创新的选择是使用 体外制造的“心脏补丁”用于体内植入。独立阶段提出的研究 该奖项旨在解决与这种心脏的功能和最终使用有关的2个关键问题 贴片：1）仿生培养环境对组织形态和功能的影响，以及2） 体外仿生工程心肌替代物对左心室功能恢复作用 心梗后本工作的总体假设是，在仿生培养中， 条件恢复MI后左心室功能优于基于细胞治疗的修复方法。的 塔夫茨大学的环境使我能够独特地解决这个假设，作为世界著名的 组织工程研究中心和分子心脏病研究所都位于附近。 这个环境将使我有机会增加我在组织方面已经相当丰富的背景 力学和组织工程方法与心脏解剖学和生理学在健康和疾病， 心脏外科技术在独立阶段，我的职业计划的延续包括 在细胞和组织培养技术以及生物反应器开发方面获得更多专业知识，同时学习新的 包括心脏外科技术和MI大鼠模型生理学评价等领域的技能。的 该项目的最终目标是利用这些技术直接比较心肌组织的功效， 在体外用目前基于细胞治疗的心脏修复方法进行工程改造， 心肌梗死后心室考虑到心脏病发病率的持续上升，这项研究尤其重要。 疾病这项研究的结果可能有助于阐明设计参数是至关重要的创造 功能性心肌体外工程，从而推进“心脏补片”的概念更接近现实

Cardiovascular disease can lead to myocardial infarction (Ml) and subsequent heart failure. There are currently a number of therapies aimed at preventing or treating heart failure post-MI. Only heart transplantation replaces infarcted myocardium to restore heart function, but there is a paucity of donor hearts and the incidence of cardiovascular disease continues to rise. A new and innovative option is the use of "heart patches" created in vitro for implantation in vivo. The research proposed in the independent phase of this award aims to address 2 critical issues pertaining to the function and eventual use of such heart patches: 1) the effect of a biomimetic culture environment on tissue morphology and function, and 2) the efficacy of myocardial equivalents biomimetically-engineered in vitro in restoring left ventricular function post-MI. The overall hypothesis of this work is that myocardium engineered in vitro in biomimetic culture conditions restores post-MI left ventricular function better than cell therapy-based methods of repair. The environment at the Tufts University uniquely positions me to address this hypothesis, as the world-renowned Tissue Engineering Research Center and Molecular Cardiology Research Institute are both located nearby. This environment will give me the opportunity to augment my already considerable background in tissue mechanics and tissue engineering methods with cardiac anatomy and physiology in health and disease and cardiac surgical techniques. The continuation of my career plan during the independent phase includes gaining more expertise in cell and tissue culture techniques and bioreactor development, while learning new skills in areas including cardiac surgical techniques and physiological evaluation in a rat model of Ml. The ultimate goal of the project is to leverage these skills to directly compare the efficacy of myocardial tissue engineered in vitro with current cell-therapy based methods of cardiac repair in restoring function to the left ventricle post-MI. This research is especially critical considering the continuing rise in incidence of heart disease. The results of this research may help elucidate design parameters that are critical to the creation of functional myocardium engineered in vitro and thus advance the concept of the "heart patch" closer to reality