Evaluation of the Efficacy of a Liquid Cast Drug-Eluting Biodegradable Stent

描述（由申请人提供）：尽管动脉支架是冠状动脉和外周动脉疾病的高效治疗方法，但其使用具有临床显著局限性。继发于新生内膜增生的支架再狭窄和动脉愈合延迟导致的支架内血栓形成仍然是主要限制。药物洗脱支架（DES）可显著降低新生内膜反应。然而，DES洗脱的抗增殖剂延迟再内皮化并损害内皮功能。为了克服这些挑战，我们开发了一种新型的液体浇铸一氧化氮（NO）洗脱可生物降解支架。本提案的总体目标是使用我们的专用三球囊导管在体内研究这种新型NO洗脱可生物降解支架。我们假设与传统支架平台相比，该技术将安全地减少支架再狭窄和血栓形成。因此，我们的具体目标是：1）确定使用我们的专用导管在猪髂动脉损伤模型中体内植入NO洗脱液体支架的最佳条件，2）评估NO洗脱液体支架与DES和裸金属支架（BMS）相比的血流动力学和生物相容性，3）评估NO洗脱液体支架的有效性。与DES和BMS相比，洗脱液体支架减少再狭窄和支架血栓形成。我们的可生物降解聚（柠檬酸二醇酯）支架将提供NO，一种血管保护分子，可舒张新鲜血管成形术的动脉，从而对抗弹性回缩，同时通过抑制新生内膜增生，血小板粘附和刺激内皮细胞生长促进长期血管愈合。我们已经证明了我们的聚合物在体内的生物相容性，优化了我们的NO洗脱聚合物的离体光聚合，证明了足够的和可定制的机械支架性能，成功地在猪动脉离体铸造支架，并与行业工程师一起开发和组装了多个原型三球囊导管。现在是时候在体内临床前动物模型中评估这种创新的支架技术了。这种支架技术有可能克服现有市售金属支架以及预成型可生物降解支架的缺点。因此，这种新颖和创新疗法的开发将直接挑战使用永久性金属支架治疗严重动脉粥样硬化的现有范例，并可能对患者护理产生重大影响。

DESCRIPTION (provided by applicant): Despite being a highly efficacious treatment for coronary and peripheral artery disease, the use of arterial stents has clinically significant limitations. Stent restenosis secondary to neointimal hyperplasia and stent thrombosis due to delayed arterial healing remain the primary limitations. The neointimal response has been dramatically reduced by drug-eluting stents (DES). However, the antiproliferative agents eluted by DES delay re-endothelialization and impair endothelial function. To overcome these challenges, we have developed a novel liquid cast nitric oxide (NO)-eluting biodegradable stent. The overall goal of this proposal is to study this novel NO-eluting biodegradable stent using our specialty triple-balloon catheter in vivo. We hypothesize that this technology will safely reduce stent restenosis and thrombosis compared to conventional stent platforms. Accordingly, our specific aims are to: 1) determine the optimal conditions to polymerize the NO-eluting liquid stent in vivo in a porcine iliac artery injury model using our specialty catheter~ 2) assess the hemodynamic and biologic compatibility of the NO-eluting liquid stent compared to DES and bare metal stents (BMS) ~ and 3) assess the efficacy of the NO-eluting liquid stent in reducing restenosis and stent thrombosis compared to DES and BMS. Our biodegradable poly (diol citrate) stent will deliver NO, a vasoprotective molecule that will vasodilate the freshly angioplastied artery thereby combating elastic recoil, and simultaneously promote long-term vascular healing by inhibiting neointimal hyperplasia, platelet adhesion, and stimulating endothelial cell growth. We have already demonstrated the biocompatibility of our polymer in vivo, optimized our NO-eluting polymer for photo-polymerization ex vivo, demonstrated sufficient and customizable mechanical stent properties, successfully cast stents in porcine arteries ex vivo, and developed and assembled multiple prototype triple balloon catheters with industry engineers. It is now time to evaluate this innovative stent technology in a preclinical animal model in vivo. This stent technology has the potential to overcome the shortcomings of existing commercially available metal stents as well as preformed biodegradable stents. Thus, development of this novel and innovative therapy will directly challenge the existing paradigm of using permanent metal stents to treat severe atherosclerosis and could have a large impact on patient care.