Abstract

Introduction: We previously identified LXW7, a specific integrin αvβ3 targeting ligand capable of selectively capturing endothelial progenitor cells (EPCs) and endothelial cells (ECs), and developed a parylene-based conformal coating technology to covalently bind LXW7 to prosthetic materials. LXW7-coated grafts have demonstrated successful capture of EPCs and ECs, which then promotes endothelialization of prosthetic materials. This study aims to assess the function of LXW7 coating on interposition polytetrafluoroethylene (ePTFE) graft thrombus formation and patency in a large animal model. Methods: 8 Yorkshire pigs underwent implantation of bilateral iliac artery interposition bypasses using control ePTFE grafts and LXW7-coated ePTFE grafts. Each animal served as its own control and the implanting surgeon and experimental team were blinded to treatment and evaluations. Computed Tomography Angiogram (CTA) immediately post-operatively, 3 weeks, and 6 weeks post-implantation. After final CTA, animals were sacrificed and grafts were harvested. The project proceeded following the approval of United States Air Force, David Grant Medical Center Institutional Animal Care & Use Committee. Results: 6 animals were included in final analysis, with 2 excluded due to complications during their surgical and post-operative course requiring euthanasia. Native artery diameter was 4.08mm for the control grafts and 4.17mm for LXW7-coated grafts (p=0.296). Post-procedure CTA demonstrated procedural success for all 6 pigs with no evidence of thrombus or stenosis. At 3 week imaging, all grafts remained patent. 6 week imaging, all LXW7-coated grafts were patent without evidence of thrombus or stenosis while 4 of the 6 control grafts were either fully or partially thrombosed. Repeated measures mixed effects analysis demonstrated significantly improved patency over time with LXW7 coated grafts (p<0.001). Conclusion: This is the first study investigating LXW7-coating on prosthetic vascular graft patency in a large animal model. We demonstrate significantly improved graft patency use of LXW7-coating, suggesting promise as an adjunct for prosthetic grafts in vascular bypass applications.

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