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）：尽管对冠状动脉和周围动脉疾病进行了高效的治疗方法，但动脉支架的使用在临床上具有显着的局限性。支架再狭窄继发于新的增生和支架血栓形成因动脉愈合而导致的支架血栓形成仍然是主要局限性。通过药物洗脱支架（DES）大大降低了新的反应。然而，通过DES延迟重新皮层化和损害内皮功能洗脱的抗增殖剂。为了克服这些挑战，我们已经开发了一种新型的液体铸氧化氧化氧化氮（NO），可以利用可生物降解的支架。该提案的总体目标是使用我们在体内的特种三球导管研究这种新颖的无生物降解支架。我们假设与传统支架平台相比，这项技术将安全减少支架再狭窄和血栓形成。因此，我们的具体目的是：1）确定使用我们的专业导管〜2）评估无液态液体的血液动力学和生物学兼容性的最佳条件，以在牛仔动脉损伤模型中在体内进行聚合的最佳条件。支架血栓形成与DES和BMS相比。我们的可生物降解的聚（柠檬酸二醇）支架将不提供否，这是一种血管保护分子，可使新鲜血管碎裂的动脉造成血管造成的分子，从而抗击弹性后坐力，并通过抑制新内在的复杂性，血小板粘附和刺激性细胞生长，同时促进长期的血管愈合。 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.现在是时候在体内的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的市售金属支架以及预先形成的可生物降解支架的缺点。因此，这种新颖的创新疗法的发展将直接挑战使用永久金属支架治疗严重动脉粥样硬化的现有范式，并可能对患者护理产生很大的影响。