ACTIVE PATCH THERAPY FOR ISCHEMIC MITRAL REGURGITATION

描述（由申请人提供）： 缺血性二尖瓣返流（MR）是心肌梗死的常见并发症，其晚期死亡率增加一倍。 它基本上是由受损的心脏壁的扭曲引起的，这会拉动二尖瓣小叶并限制其关闭的能力。 我们已经证明，通过外科手术或外部补片重塑心脏可以逆转这一过程;然而，这些方法覆盖了大部分心脏，需要心内直视手术。 我们建议探索两种创新的方法来实现这一目标，并为患者带来额外的益处：（1）通过自体成肌细胞移植到梗死壁中进行组织再生，通过变得更厚，可以抵抗变形并呈现更正常的形状，从而减轻二尖瓣小叶上的张力（具有微创实施潜力的方法）;以及（2）使用由基于聚合物的人造肌肉组成的外部贴片，以提供正常形状（较少MR）以及辅助心脏功能的收缩和放松的额外益处。人造肌肉的发展需要对替代材料和设计进行计算、体外和体内测试。 两种方法都将在建立的缺血性MR模型中进行测试，并进行适当的对照。 这些研究是合理的，有前途的结果与被动补丁，并需要探索性的工作，以开发功能补丁。 为了实现临床问题和开发技术的综合，该提案将汇集几个领域的专业知识：通过波士顿和巴黎实验室提供的三维超声心动图对动物模型中的二尖瓣进行定量分析;成肌细胞收获和心肌再生（Menasche教授）;开发创造人造肌肉的创新方法（麻省理工学院的Hunter教授）;以及心血管手术（Vlahakes博士和Menasche教授）。

DESCRIPTION (provided by applicant): Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction that doubles its late mortality. It is fundamentally caused by distortion of the damaged heart wall, which pulls on the mitral valve leaflets and restricts their ability to close. We have shown this process can be reversed by re-shaping the heart surgically or with an external patch; these approaches, however, immobilize a large portion of the heart and require open-heart surgery. We propose exploring two innovative ways to achieve this goal with additional benefits to the patient: (1) tissue regeneration by autologous myoblast transplantation into the infarcted wall, which, by becoming thicker, would resist deformation and assume a more normal shape that relieves the tension on the mitral leaflets (an approach with potential for minimally invasive implementation); and (2) using an external patch composed of polymer-based artificial muscle to provide both normal shape (less MR) and the additional benefits of contraction and relaxation to assist heart function. The artificial muscle development will require computational, in vitro and in vivo testing of alternative materials and designs. Both approaches will be tested in established models of ischemic MR with appropriate controls. These studies are justified by promising results with passive patches, and require exploratory work to develop functional patches. To achieve this synthesis of clinical problem and developmental techniques, this proposal will bring together expertise in several areas: quantitative analysis of the mitral valve in animal models by three-dimensional echocardiography, available in both Boston and Paris laboratories; myoblast harvesting and myocardial repopulation (Professor Menasche); developing innovative approaches to create artificial muscle (Professor Hunter at MIT); and cardiovascular surgery (Dr. Vlahakes and Prof. Menasche).