A Novel Polymeric Valve for Transcatheter Aortic Valve Replacement

项目总结：一种用于经导管主动脉瓣置换术的新型聚合物瓣膜 微创经导管主动脉瓣置换术（TAVR）已成为治疗 严重主动脉瓣狭窄（AS）无法手术患者的临床需求未得到满足。最近的纵向随访研究 然而，TAVR患者表示，该手术和相关技术可能导致严重不良反应， 事件目前的技术基于适用于TAVR的组织瓣膜，但不是专门为TAVR设计的。这些可能 在卷曲和展开过程中受到损伤，易受“骨样”钙化沉积影响， 有限的耐久性。我们的团队开发了一种新型阀门，专门用于解决 TAVR瓣膜在其生命周期中将遇到的挑战，从压握到展开和长期性能 在原地。它结合了（i）新的聚合物技术xSIBS，其结合了上级生物稳定性以及 优良的机械性能，和（ii）一种新的设计优化方法的小叶轮廓，以提高 血液动力学、耐久性和抗血栓性能。 我们的广泛目标是开发一种可行且耐用的TAVR瓣膜，为现有的TAVR瓣膜提供真实的替代方案。 生物假体主动脉瓣，并允许长期解决方案适用于更广泛的人群。这 I期STTR项目由斯托尼布鲁克大学和PolyNova心血管公司合作，旨在 将我们现有的新型聚合物人工心脏瓣膜转移到TAVR应用中，提供概念验证。这将 在四个目标中进行测试：目标1通过计算机模拟分析标准和患者的流体动力学性能- 特定解剖结构，量化其血栓形成潜力，并将其与市售瓣膜进行比较。Aim 2测试 体外流体动力学性能，使用标准和患者特异性解剖结构，并评估对 由于瓣膜卷曲而导致的聚合物。目的3通过血小板量化瓣膜的抗血栓性特征 在生理流动条件下活化。目的4评价耐久性性能和钙化 加速磨损试验条件下的敏感性。 上述目标的成功实现将导致主动脉瓣疾病治疗的突破， 提供负担得起的、长期的、微创的解决方案， 人口

Project Summary: A Novel Polymeric Valve for Transcatheter Aortic Valve Replacement Minimally invasive transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for the unmet clinical need of inoperable patients with severe aortic stenosis (AS). Recent longitudinal follow-up studies of TAVR patients however indicate that this procedure and associated technology may result in serious adverse events. Current technology is based on tissue valves adapted to, but not specifically designed for TAVR. Those may sustain damage during crimping as well as deployment, are susceptible to ‘bone-like’ calcific deposition, and suffer from limited durability. Our group has developed a novel valve that is specifically designed to tackle the numerous challenges that a TAVR valve will meet during its life cycle, from crimping to deployment and long term performance in situ. It incorporates (i) novel polymer technology, xSIBS, which combines superior bio-stability together with excellent mechanical properties, and (ii) a novel design optimization methodology of the leaflets profile for enhanced hemodynamic, durability, and thromboresistance performance. Our broad objective is to develop a viable and durable TAVR valve that will propose a real alternative to existing bioprosthetic aortic valves, and allow a long-term solution adequate for broader segment of the population. This Phase I STTR project, in a collaboration between Stony Brook University and PolyNova Cardiovascular Inc, aims to shift our existing novel polymeric prosthetic heart valve to a TAVR application, providing proof-of-concept. This will be tested in four aims: Aim 1 analyses the hydrodynamic performance in silico both in standard as well as in patient- specific anatomy, quantify its thrombogenic potential, and compares it to a commercially available valve. Aim 2 tests the hydrodynamic performance in vitro, using standard and patient-specific anatomy, and evaluates damage to the polymer as a result of valve crimping. Aim 3 quantifies the thromboresistance profile of the valve via platelet activation under physiological flow conditions. Aim 4 evaluates the durability performance and calcification susceptibility under accelerated wear testing conditions. Successful accomplishment of the above aims will lead to a breakthrough in the treatment of aortic valve diseases, providing an affordable, long-term, minimally invasive solution, enhancing the life of a much broader patient population.