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

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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.