Novel drug-eluting sutures to prevent vascular graft anastomosis stenosis

新型药物洗脱缝合线预防血管移植吻合口狭窄

• 批准号: 10085517
• 负责人: Narutoshi Hibino
• 金额: $ 32.59万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10085517
• 关键词: Adopted; Anastomosis - action; Animal Model; Animals; Arteries; Blood Cell Count; Blood Vessels; Body Weight; Bypass; Caliber; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Characteristics; Childhood; Coronary; Devices; Dose; Drug Formulations; Electrospinning; Engineering; Ensure; Formulation; Functional disorder; Gel; Gold; Growth; Hemodialysis; Human; Hyperplasia; In Vitro; Incidence; Inflammation; Kidney; Lipids; Longevity; Metabolic; Methods; Modeling; Morbidity - disease rate; Morphology; Nylons; Obstruction; Operative Surgical Procedures; Organ; Organ Transplantation; Patients; Peripheral; Pharmaceutical Preparations; Physiologic arteriovenous anastomosis; Polymers; Polypropylenes; Procedures; Process; Prosthesis; Rattus; Sheep; Sirolimus; Site; Smooth Muscle Myocytes; Spleen; Stenosis; Stents; Surgical sutures; Technology; Tensile Strength; Testing; Therapeutic; Thinness; Time; Transplantation; Vascular Graft; Vascular Smooth Muscle; Veins; Venous; Wool; antiproliferative drugs; appropriate dose; biodegradable polymer; biomaterial compatibility; controlled release; dosage; drug efficacy; drug release kinetics; graft failure; healing; improved; liver function; manufacturing process; migration; nanofiber; novel; novel therapeutics; outcome forecast; prevent; reconstruction; repaired; restenosis; side effect; surgery outcome

Project Summary Millions of anastomoses, or surgical connections between arteries or veins, are performed in vascular, transplant, and reconstruction procedures in the US each year. Neointimal hyperplasia, or proliferation and migration of vascular smooth muscles cells into the vessel lumen space, develops immediately at the site of anastomosis due to the local damage caused by the surgical procedure. The resulting stenosis, or narrowing of the vessel after the anastomosis, is the main contributor to arterial, venous, arteriovenous, and prosthetic graft failure. Preventing anastomotic stenosis is the key to long-term efficacy of all types of vascular surgery, and will improve patient prognosis. The gold standard for anastomotic surgery is to use non-absorbable sutures, like nylon or polypropylene. We hypothesize that sutures can be produced that locally release anti-proliferative drugs at the site of anastomosis for several weeks or longer, thereby preventing neointimal overgrowth and stenosis without disrupting normal surgical workflow. Used during anastomosis procedure, the suture will provide sustained release of drugs for several weeks or longer to prevent neointimal overgrowth. We describe a novel electrospinning platform capable of producing both non-absorbable and absorbable drug- eluting sutures for vascular surgery: (i) nylon sutures that are wrapped in drug-eluting and degradable, polymer nanofibers, and (ii) fully absorbable, high-strength, drug-eluting, twisted polymer nanofiber sutures. We have loaded these sutures with rapamycin, which is a promising anti-proliferative drug that has been used in combination with stents for preventing in-stent restenosis. Our preliminary results demonstrate that nanofiber- coated nylon sutures provide sustained rapamycin release that decreases neointimal hyperplasia in a rat anastomosis model in a drug dose dependent fashion for several weeks. Here, we aim to further optimize our suture formulations for drug loading and drug release to prevent neointimal hyperplasia while maintaining anastomosis repair and minimizing systemic side effects. The sutures will be evaluated in our rat anastomosis model, and the most promising candidates will be tested in a large animal model that is considered to best recapitulate the human vasculature. If successful, our sutures could serve as a platform technology for preventing stenosis in any type of organ anastomosis.

项目摘要 数以百万计的动脉或静脉之间的手术连接，是在血管， 移植和重建手术在美国每年。新生内膜增生或增殖， 血管平滑肌细胞迁移到血管腔空间中，立即在 由于外科手术造成的局部损伤，导致的狭窄，或狭窄的 吻合后的血管是动脉、静脉、动静脉和人工血管的主要来源 失败预防吻合口狭窄是所有类型血管手术长期有效的关键， 将改善患者预后。吻合手术的金标准是使用不可吸收缝线， 比如尼龙或者聚丙烯。我们假设可以生产局部释放抗增殖药物的缝线， 在吻合部位使用药物数周或更长时间，从而防止新生内膜过度生长， 狭窄而不干扰正常的手术工作流程。在吻合术期间使用，缝线将 提供持续释放药物数周或更长时间，以防止新生内膜过度生长。 我们描述了一种新型的静电纺丝平台，能够生产不可吸收和可吸收的药物， 用于血管手术的洗脱缝合线：（i）包裹在药物洗脱和可降解聚合物中的尼龙缝合线 纳米纤维，和（ii）完全可吸收的、高强度的、药物洗脱的、扭曲的聚合物缝合线。我们有 在这些缝线中加入了雷帕霉素，这是一种很有前途的抗增殖药物， 与支架组合用于预防支架内再狭窄。我们的初步结果表明， 涂层尼龙缝线提供持续的雷帕霉素释放，减少大鼠的新生内膜增生 在吻合模型中以药物剂量依赖性方式持续数周。在这里，我们的目标是进一步优化我们的 用于药物装载和药物释放以防止新生内膜增生同时维持 吻合修复和最小化全身副作用。将在我们的大鼠吻合术中对缝线进行评价 模型，最有希望的候选人将在被认为是最好的大型动物模型中进行测试。 重现了人类的血管系统如果成功，我们的缝合线可以作为一种平台技术， 防止任何类型的器官吻合术中的狭窄。