Development of a Hybrid Dynamic Stent

描述(申请人提供)：尽管药物洗脱支架已经成功地降低了冠状动脉应用中的再狭窄率，但它们在外周应用中还没有被证明是有效的。有证据表明，再狭窄是由机械因素驱动的，支架置入会影响动脉周围的机械环境。更周到地考虑支架设计对机械环境的影响，可以最大限度地减少支架置入的不良影响。例如，支架的几何形状可以进行优化，以最大限度地减少对动脉壁施加的应力，阻止支架植入过程中产生的内膜瓣，抑制血小板聚集，促进再内皮化，最大限度地减少通过支架区域的血流干扰，并最大限度地减少支架与动脉壁之间的顺应性不匹配。值得注意的是，从设计的角度来看，上述的一些顾虑会导致相互竞争的利益，例如，最适合于最小化壁应力和促进再内皮化的几何形状最不适合保留内膜瓣和抑制血小板聚集。幸运的是，这些担忧在支架置入后的不同时间段最为显著。CorInnova正在开发一种支架技术，该技术可以随着时间的推移改变几何和机械性能，以便在最重要的时间内针对给定的问题对设计进行优化。请注意，药物洗脱支架通常装载有抗增殖药物，旨在调和支架植入过程本身的不良后果。这些后果本质上主要是机械性的。CorInnova的方法是通过对机械环境破坏性较小的设计特征将这些不利后果降至最低，从而减少对补偿性药物的需求。这项申请的总体目标是建立一种金属/聚合物混合支架的概念验证，用于治疗药物洗脱支架失败的周围血管疾病。我们将通过设计和测试两种技术的组合来解决这个问题，部分可降解支架和血流动力学良好的支架，作为一种单一的设计，共同克服外围支架的突出问题。因此，这项建议的主要重点是评估我们独特的支架设计的临床和工程基础，为相关动物模型的临床前测试做准备。 公共卫生相关性：这项应用的总体目标是检查金属/聚合物复合支架治疗外周血管疾病的疗效。使用支架治疗闭塞性外周血管疾病，特别是在下肢，涉及冠状动脉应用中未曾见过的挑战，这导致了更高的临床失败率。因此，这项建议的主要重点是评估我们独特的支架设计的临床和工程基础，为相关动物模型的临床前测试做准备。

DESCRIPTION (provided by applicant): Though drug-eluting stents have successfully reduced restenosis rates in coronary applications, they have not proven as effective in peripheral applications. There is evidence that suggests that restenosis is driven by mechanical factors and that stent placement affects the mechanical environment about the artery. The adverse effects of stent placement can be minimized with more thoughtful consideration of the influence that the stent design has on the mechanical environment. For example, stent geometry can be optimized to minimize the stresses imposed in the artery wall, hold back intimal flaps that result from the stenting process, inhibit platelet aggregation, promote re-endothelialization, minimize flow disturbances through the stented region and minimize the mismatch in compliance between the stent and artery wall. It is important to note that some of the aforementioned concerns result in competing interests from the design perspective, e.g. the geometries that are best suited to minimize wall stresses and promote re-endothelialization are least suited to retain intimal flaps and inhibit platelet aggregation. Fortunately, these concerns are most significant along different time frames post-stent deployment. CorInnova is developing a stent technology that changes geometry and mechanical properties with time such that the design can be optimized for a given concern during the time that said concern is most significant. Note that drug-eluting stents are typically loaded with anti-proliferative medications that are designed to reconcile adverse consequences of the stenting process itself. These consequences are primarily mechanical in nature. CorInnova's approach is to minimize these adverse consequences via design features that are less devastating to the mechanical environment and thereby reduce the need for compensatory medication. The overall goal of this application is to establish proof-of-concept for a hybrid metal/polymer stent for the treatment of peripheral vascular disease where drug-eluting stents have failed. We will address this problem by designing and testing a combination of two technologies, a partially degradable stent and hemodynamically favorable stent, as a single design that collectively overcomes outstanding problems in peripheral stenting. As such, the primary focus of this proposal is to evaluate the clinical and engineering foundation of our unique stent designs to prepare for pre-clinical testing in a relevant animal model. PUBLIC HEALTH RELEVANCE: The overall goal of this application is to examine the efficacy of a hybrid metal/polymer stent for the treatment of peripheral vascular disease. Treatment of occlusive peripheral vascular disease with stents, particularly in the lower limbs, involves challenges not seen in coronary applications that have led to much higher clinical failure rates. As such, the primary focus of this proposal is to evaluate the clinical and engineering foundation of our unique stent designs to prepare for pre-clinical testing in a relevant animal model.