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.

项目总结/摘要 外周动脉疾病（PAD）影响美国近1200万人。最常见的一 外科治疗是外周动脉旁路移植术（PABG）。有些患者适合进行侵入性较低的 治疗选择，如血管成形术，但钙化病变的患者没有。在接受PABG的患者中， 大约20%在第一年内失败，50%在5年内失败。该提案侧重于改善成果 需要PABG的患者。 目前的PABG手术存在几个主要缺点：吻合的质量非常低， 这取决于外科医生的经验，并且静脉移植物不适合高压、高流量 动脉循环的环境。该提案评估了形状记忆聚合物（SMP）外部静脉 wrap（SelfWrap）来解决这些缺点。SelfWrap是以规定的角度制造的， 可以支撑缝线的动脉和静脉分支，可能减少对缝线质量的依赖 和手术经验更重要的是，SelfWrap在第一次使用时为静脉提供机械支撑， 暴露于动脉压。减轻静脉移植物中的壁张力可以减少新生内膜增生（NH）， 从而减轻移植失败的风险。SelfWrap的形状记忆特性是一个关键方面， 使该装置能够与患者特定的血管解剖结构形状配合， 支持，即使在整个心动周期中动脉和静脉分支搏动。 评价SelfWrap作为动静脉瘘血管周围包裹物时在绵羊中收集的初步结果 (AVF)用于血液透析通路支持这些声明。在第28天，使用SelfWrap治疗的AVF 与未经治疗的AVF相比，流速显著更高，血管直径更大。 然而，如果SelfWrap具有显著的长期降解，则这些都与SelfWrap的商业化无关 和/或可替换的问题。出于这个原因，生物降解，可降解物测试后的风险评估， 在本提案中评价了6个月植入的生物相容性结果。这些测试将遵循 在早期评估细胞毒性、急性全身毒性和植入式生物相容性的授予前活动 时间点。FDA的突破性器械认定决定以及与 FDA进一步告知我们的监管测试策略也将在授标前完成。除了第一个目标， 将在兔模型PABG模型中收集组织学、血液动力学和生物力学数据，以进一步 确认SelfWrap器械在PABG环境中的解剖学和生理学性能良好。 成功完成本提案中的目标将通知VenoStent，Inc.。如果需要进行任何更改， SelfWrap的制造工艺或设计在继续进行其他GLP生物相容性试验之前， 制造工作，以及在非GLP和GLP大型动物PABG模型中的试验。