Biodegradability and Biocompatibility of a Shape Memory Polymer Wrap to Improve Saphenous Vein Graft Patency in Peripheral and Coronary Artery Bypass Grafting Surgeries

形状记忆聚合物包裹物的生物降解性和生物相容性可改善周围动脉和冠状动脉搭桥手术中隐静脉移植物的通畅性

• 批准号: 9909182
• 负责人: Timothy C Boire
• 金额: $ 29.99万
• 依托单位: VENOSTENT, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2021-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909182
• 关键词: Achievement; Acute; Address; Affect; American; Anastomosis - action; Anatomy; Angioplasty; Animal Model; Animals; Area; Arteries; Arteriovenous fistula; Attenuated; Award; Bilateral; Biodegradation; Biomechanics; Blood Circulation; Blood Vessels; Blood flow; Body Temperature; Bypass; Caliber; Cardiac; Cessation of life; Characteristics; Chronic; Coronary Artery Bypass; Custom; Data; Dependence; Devices; Distal; Ensure; Environment; Evaluation; Exhibits; Exposure to; Family suidae; Feedback; Financial Hardship; Geometry; Harvest; Health Care Costs; Hemodialysis; Histologic; Hyperplasia; Implant; In Vitro; Inflammatory Response; Influentials; Lead; Left; Lesion; Mechanics; Memory; Modeling; Molds; Operative Surgical Procedures; Organ Transplantation; Oryctolagus cuniculus; Patients; Pattern; Peripheral; Peripheral arterial disease; Physiologic pulse; Physiological; Polymers; Procedures; Research; Risk; Risk Assessment; Safety; Saphenous Vein; Second Look Surgery; Shapes; Sheep; Stents; Stress; Surface; Surgeon; Surgical sutures; Testing; Time; TimeLine; United States; Vein graft; Veins; Venous; artery occlusion; biomaterial compatibility; calcification; caprolactone; cytotoxicity; design; experience; experimental study; flexibility; graft failure; hemodynamics; hospital readmission; implantation; improved; improved outcome; in vivo; infection risk; manufacturing process; meetings; melting; mimetics; neovascularization; phase 2 testing; pressure; systemic toxicity; thrombogenesis; viscoelasticity

PROJECT SUMMARY/ABSTRACT Peripheral artery disease (PAD) affects nearly 12 million people in the United States. One of the most common surgical therapies is peripheral artery bypass grafting (PABG). Some patients are eligible for less invasive treatment options like angioplasty, but patients with calcified lesions are not. In patients that do receive PABG, approximately 20% fail within the first year and 50% within 5 years. This proposal focuses on improving outcomes in patients who require PABG. There are a couple major shortcomings in current PABG procedures: the quality of the anastomosis is highly dependent on surgeon experience, and vein grafts are not conditioned for the high pressure, high flow environment of the arterial circulation. This proposal evaluates a shape memory polymer (SMP) external vein wrap (SelfWrap) to address these shortcomings. SelfWrap is manufactured with a prescribed angle between the artery and vein branches which can support the sutures, possibly reducing dependence on quality of the sutures and surgical experience. More importantly, SelfWrap provides mechanical support to the vein upon its first exposure to arterial pressures. Mitigating wall tension in the vein graft can reduce neointimal hyperplasia (NH), thereby alleviating risk of graft failure. The shape memory characteristics of SelfWrap are a critical aspect that enables the device to form-fit to the patient-specific vascular anatomy and provide non-constrictive mechanical support, even as the artery and vein branches pulse throughout the cardiac cycle. Preliminary results collected in sheep when evaluating SelfWrap as a perivascular wrap on arteriovenous fistulas (AVF) used for hemodialysis access support these claims. At 28 days, AVFs treated with SelfWrap had significantly higher flow rates and larger vessel diameters than untreated AVFs. However, none of this is relevant towards commercializing SelfWrap if it has significant long-term degradation and/or leachables issues. For this reason, biodegradation, a risk assessment following leachables testing, and biocompatibility results from a 6-month implantation are evaluated in the present proposal. These tests will follow pre-award activities assessing cytotoxicity, acute systemic toxicity, and implantable biocompatibility at earlier timepoints. A Breakthrough Devices Designation decision from the FDA and a pre-submission meeting with the FDA to further inform our regulatory testing strategy will also be completed pre-award. In addition to the first aim, histological, hemodynamic, and biomechanical data will be collected in a rabbit model PABG model to further validate that the SelfWrap device performs well in the PABG environment, both anatomically and physiologically. Successful completion of the aims in this proposal will inform VenoStent, Inc. if there are any changes needed for SelfWrap’s manufacturing process or design prior to continuing onto other GLP biocompatibility tests, furthering manufacturing efforts, and testing in non-GLP and GLP large animal PABG models.

项目摘要/摘要 在美国，周围动脉疾病（PAD）影响了近1200万人。最常见的 手术疗法是外周动脉搭桥术（PABG）。有些患者有资格减少侵入性 诸如血管成形术等治疗方案，但且损伤的患者却没有。在接受PABG的患者中， 大约在第一年失败了20％，在5年内失败了50％。该建议重点是改善结果 在需要PABG的患者中。 当前的PABG程序存在两个主要缺点：吻合的质量很高 取决于外科医生的经验，静脉移植不适合高压，高流量 动脉循环的环境。该建议评估形状内存聚合物（SMP）外部静脉 包装（自我包装）来解决这些缺点。自面包装是在规定的角度制造的 可以支撑缝合线的动脉和静脉分支，可能会降低对缝线质量的依赖 和手术经验。更重要的是，Selfranap在第一个时为静脉提供机械支持 暴露于动脉压力。减轻静脉移植物中的壁张力可以减少新内膜增生（NH）， 从而减轻了移植失败的风险。自我包装的形状记忆特征是一个关键方面 使该设备能够与患者特异性的血管解剖结构形成，并提供非收缩的机械性 支持，即使动脉和静脉分支在整个心脏周期中脉搏。 在评估自我包装作为动静脉瘘的周期缠绕时，在绵羊中收集的初步结果 （AVF）用于血液透析访问支持这些主张。在28天，用自动处理治疗的AVF 与未处理的AVF相比，流速明显更高和更大的容器直径。 但是，如果有重大的长期降级，这些都不是与商业化自面的商业化相关的 和/或利用问题。因此，生物降解，杠杆测试后的风险评估以及 在本提案中评估了6个月植入的生物相容性结果。这些测试将遵循 预先评估细胞毒性，急性全身毒性和可植入生物相容性的活动 时间点。 FDA的突破设备指定决定，并与 FDA要进一步告知我们的监管测试策略，也将完成预授予。除了第一个目标， 组织学，血液动力学和生物力学数据将在兔模型模型中收集以进一步 验证自动包装设备在解剖和身体上的PABG环境中表现良好。 在此提案中成功完成目标将为您提供静脉注册，Inc.。如果需要任何更改 在继续进行其他GLP生物相容性测试之前，SelfWrap的制造过程或设计 在非GLP和GLP大型动物PABG模型中进行制造工作以及测试。