Effects of Cyclic Peptide LXW7 Coating on Short-term Vascular Graft Patency Using a Porcine (Sus scrofa) Model

Abstract

We previously identified LXW7, a specific integrin αvβ3 targeting ligand capable of selectively capturing endothelial progenitor cells and endothelial cells, and developed a parylene-based conformal coating technology to covalently present LXW7 to prosthetic materials. In previous in vitro and in vivo studies, LXW7-coated grafts have demonstrated successful capture of endothelial progenitor cells and endothelial cells, which then promotes re-endothelialization of these prosthetic materials. This study aims to assess the function of LXW7 coating on interposition expanded polytetrafluoroethylene (ePTFE) graft thrombus formation and patency in a large animal model. Eight female Yorkshire pigs underwent transperitoneal implantation of bilateral iliac artery interposition bypasses using control plain ePTFE grafts (inner diameter 6 mm) 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. The animals underwent computed tomography angiography (CTA) immediately postoperatively and at 3 and 6 weeks postimplantation. After final CTA imaging, animals were sacrificed and interposition grafts were harvested for histological evaluation. The project proceeded following the approval of United States Air Force, David Grant Medical Center Institutional Animal Care and Use Committee. Six animals were included in final analysis, with two excluded due to complications during their surgical and postoperative course requiring euthanasia. Average native artery diameter was 4.08 mm for the control grafts and 4.17 mm for LXW7-coated grafts (P = .296). Average clamp time was similar between groups (60 minutes for the control grafts vs 52 minutes on the LXW7-coated grafts; P = .291). The immediate postprocedure CTA demonstrated procedural success for all six pigs with no evidence of thrombus or stenosis. At the 3-week imaging, all grafts remained patent. At the 6-week imaging, all six LXW7-coated grafts were patent without evidence of thrombus or stenosis while four of the six control grafts were either fully or partially thrombosed. Repeated measures mixed effects analysis demonstrated significantly improved patency over time with LXW7 coated grafts (P < .001) (Figure). This is the first study using CTA to investigate the impact of LXW7 coating on prosthetic vascular graft patency in a clinically relevant large animal model. The findings demonstrate significantly improved graft patency over time with use of LXW7 coating, suggesting promise as a potential adjunct to clinical outcomes with prosthetic grafts in vascular bypass applications.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)