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

描述(申请人提供)：尽管动脉支架是治疗冠状动脉和外周动脉疾病的一种非常有效的治疗方法，但它在临床上有很大的局限性。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血栓形成仍然是主要的限制因素。药物洗脱支架(DES)显著降低了血管内膜的反应。然而，DES洗脱的抗增殖剂延迟了再内皮化并损害了内皮功能。为了克服这些挑战，我们开发了一种新型的液态铸造一氧化氮(NO)洗脱生物可降解支架。这项建议的总体目标是在体内使用我们的特殊三球囊导管研究这种新型的无洗脱生物可降解支架。我们假设，与传统的支架平台相比，这项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聚合非洗脱液体支架的最佳条件~2)比较非洗脱液体支架与DES和裸金属支架(BMS)的血流动力学和生物相容性~3)评估与DES和BMS相比，非洗脱液体支架在减少再狭窄和支架血栓形成方面的有效性。我们的生物可降解聚柠檬酸二醇支架将产生一氧化氮，这是一种血管保护分子，将扩张新鲜血管成形的动脉，从而对抗弹性回缩，同时通过抑制新生内膜增生、血小板黏附和刺激内皮细胞生长来促进长期血管愈合。我们已经证明了我们的聚合物在体内的生物相容性，优化了我们的非洗脱聚合物用于体外光聚合，展示了足够和可定制的机械支架性能，成功地在体外将支架浇铸在猪动脉中，并与行业工程师一起开发和组装了多个原型三重球囊导管。现在是时候在活体动物模型中评估这项创新的支架技术了。这种支架技术有可能克服现有商用金属支架以及预制生物可降解支架的缺点。因此，这种新的创新疗法的发展将直接挑战现有的使用永久性金属支架治疗严重动脉粥样硬化的范例，并可能对患者的护理产生重大影响。

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.