Auxetic Support Device for Chronic Myocardial Infarction

项目摘要 在美国，大约每40秒就有一人发生心肌梗死（MI）。虽然死亡率 由于急性心肌梗死在过去二十年中有所减少，长期后果和合并症 与慢性心肌梗死相关的风险增加。在许多情况下，MI后左心室（LV）重构表现为 LV结构和功能的进行性变化。这种重塑启动了一个退行性循环， 梗塞区域周围改变的心肌壁力学导致心脏进行机械补偿， 结果对梗塞区造成更大的压力。因此，左心室重构是大约 所有心力衰竭（HF）病例的70%，每年约有10万美国人死亡。当前治疗 慢性MI、HF和LV重塑的治疗包括药物治疗，如ACE抑制剂和β- 阻滞剂、外部机械心室辅助装置（VAD）或侵入性冠状动脉血运重建 程序.这些干预措施是高度侵入性和/或权宜之计，需要持续的局部 调节梗死部位的心肌力学。该提案利用了拉胀材料， 当被拉伸时，反直觉地变得更厚而不是更薄，以提供恢复泵送功能的手段 心脏的梗塞区域通过将拉胀心室支持装置（auxVSD）固定到扩张装置， 梗死组织，我计划利用目前浪费在非跳动梗死的能量来代替拉伸， 扩大一个辅助室间隔缺损，这反过来又会压迫心肌，导致射血 心脏收缩期的血液目标1将集中在潜在的拉胀结构的设计，制造和测试 和材料。机械模拟将用于识别具有有利的力学性能的拉胀结构。 这是由于拉胀效应引起的位移和力的组合。同时，物理模型将 制造用于体外机械测试，以告知模拟的真实世界可行性，并提供 关于auxVSD在体内动物模型中的预期性能的初步信息。在Aim中 2将在慢性MI和LV扩张的动物模型中测试auxVSD的功效，以证明 通过对心肌力学的动态调节，改善梗死后心功能 地区总的来说，这个项目的设计是翻译和高度交叉学科的性质。此外，委员会认为， 更好地理解与疾病发作和进展相关的组织和器官水平的变化， MI将通过先进的心脏成像来指导和验证这项研究。这些研究不仅提供 一个严格的多学科综合培训平台，包括生物医学设备设计，心脏机制， 疾病，计算建模和平移成像，但也将弹射的职业生涯，重点是 为心血管和相关疾病开发新的、技术驱动的治疗策略。

PROJECT SUMMARY Approximately every 40 seconds, someone will suffer a myocardial infarction (MI) in the US. While mortality due to acute MI has decreased over the past two decades, long-term consequences and comorbidities associated with chronic MI are increasing. In many cases, post-MI left ventricular (LV) remodeling manifests as progressive changes in LV structure and function. This remodeling initiates a degenerative cycle in which altered myocardial wall mechanics around the infarcted region cause the heart to mechanically compensate, resultantly placing still more strain on the infarct. Consequently, LV remodeling is the cause of approximately 70% of all heart failure (HF) cases, which kill approximately 100,000 Americans each year. Current treatments for chronic MI, HF, and LV remodeling include pharmacological treatments such as ACE-inhibitors and β- blockers, external mechanical ventricular assist devices (VADs), or invasive coronary revascularization procedures. These interventions are highly invasive and/or stopgap remedies, requiring continuous local modulation of the myocardial mechanics at the infarct. This proposal leverages auxetic materials, which counterintuitively get thicker rather than thin when stretched, to provide a means of restoring pumping function to the infarcted region of the heart. By fixing an auxetic ventricular support device (auxVSD) to the expanding, infarcted tissue, I plan to harness the energy currently wasted in the nonbeating infarct to instead stretch and expand an auxVSD, which would in turn stiffen and press against the myocardium, contributing to the ejection of blood during systole. Aim 1 will focus on the design, fabrication, and testing of potential auxetic structures and materials. Mechanical simulations will be used to identify auxetic structures that possess a favorable combination of displacement and force due to the auxetic effect. Concurrently, physical models will be fabricated for in vitro mechanical testing to inform the real-world feasibility of the simulations as well as provide preliminary information regarding the expected performance of an auxVSD in an in vivo animal model. In Aim 2 the efficacy of an auxVSD will be tested in an animal model of chronic MI and LV expansion to demonstrate its improvement of cardiac function through the dynamic modulation of myocardial mechanics in the infarcted region. Overall, this project design is both translational and highly-cross disciplinary in nature. Furthermore, improved understanding of the tissue- and organ-level changes associated with the onset and progression of MI will guide and validate this research through advanced cardiac imaging. These studies will not only provide a platform for rigorous multi-disciplinary integrated training in biomedical device design, mechanisms of cardiac disease, computational modeling, and translational imaging, but will also catapult a career that is focused on developing novel, technology-driven therapeutic strategies for cardiovascular and related diseases.