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

液体铸型药物洗脱生物可降解支架的功效评价

• 批准号: 8695111
• 负责人: Mazen Albaghdadi
• 金额: $ 5.89万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695111
• 关键词: Adhesions; Affect; American; Anatomy; Animal Model; Area; Arteries; Atherosclerosis; Balloon Angioplasty; Biocompatible Materials; Biomedical Engineering; Blood Platelets; Blood Vessels; Cardiology; Cardiovascular Diseases; Catheters; Citrates; Clinical; Coronary; Coronary Arteriosclerosis; Development; Disease; Drug Delivery Systems; Electrical Engineering; Endothelial Cells; Engineering; Environment; Family suidae; Fellowship; Foundations; Future; Glycols; Goals; Healed; Health; Hyperplasia; In Vitro; Individual; Industry; Inflammatory; Injury; Innovative Therapy; Intervention; Knowledge; Lead; Left; Liquid substance; Mechanics; Metals; Modeling; Nature; Nitric Oxide; Patient Care; Patients; Peripheral arterial disease; Pharmaceutical Preparations; Physicians; Polymers; Prevalence; Problem Solving; Property; Prosthesis; Public Health; Qualifying; Research; Research Proposals; Scientist; Secondary to; Solid; Stents; Surface; Surgeon; System; Technical Expertise; Technology; Testing; Therapeutic; Thrombosis; Time; Training; Translating; Translational Research; Work; antiproliferative agents; base; biomaterial compatibility; career; cell growth; clinically significant; combat; design; efficacy evaluation; healing; hemodynamics; iliac artery; improved; in vivo; innovation; medical specialties; multidisciplinary; novel; percutaneous coronary intervention; polymerization; post-doctoral training; pre-clinical; preclinical study; prototype; public health relevance; radiologist; response; restenosis; skills

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.

描述（由申请人提供）：尽管动脉支架是治疗冠状动脉和外周动脉疾病的高效方法，但动脉支架的使用在临床上具有显着的局限性。继发于新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。药物洗脱支架 (DES) 显着降低了新内膜反应。然而，DES 洗脱的抗增殖剂会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液态一氧化氮（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业三球囊导管在体内研究这种新型 NO 洗脱生物可降解支架。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聚合NO洗脱液体支架的最佳条件〜2）评估NO洗脱液体的血流动力学和生物相容性支架与 DES 和裸金属支架 (BMS) 相比 ~ 和 3) 评估与 DES 和 BMS 相比，NO 洗脱液体支架在减少再狭窄和支架血栓形成方面的功效。我们的可生物降解聚（柠檬酸二醇）支架将输送 NO，这是一种血管保护分子，可以使新血管成形的动脉血管舒张，从而对抗弹性回缩，同时通过抑制新内膜增生、血小板粘附和刺激内皮细胞生长来促进长期血管愈合。我们已经在体内证明了聚合物的生物相容性，优化了用于离体光聚合的NO洗脱聚合物，证明了足够的和可定制的机械支架性能，在离体猪动脉中成功铸造了支架，并开发和组装了多个原型三重球囊与行业工程师一起使用导管。现在是在临床前动物模型体内评估这种创新支架技术的时候了。该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。