Ascorbate elastomer-coated ePTFE grafts inhibit neointimal hyperplasia and enhance vascular healing

Severe peripheral arterial disease (PAD) is often treated with surgical bypass grafting using autologous vein. When veins are unavailable, small-diameter expanded polytetrafluoroethylene (ePTFE) grafts are used but are associated with long-term poor performance. To address this, we developed poly(1,8-octanediol-co-citrate-co-ascorbate) (POCA) elastomer coatings for small-diameter ePTFE grafts that indirectly release nitric oxide <i>via</i> decomposition of circulating S-nitrosothiols (RSNO). Graft <i>in vivo</i> efficacy was assessed using a guinea pig aortic interposition model to evaluate neointimal formation. After 4 weeks, POCA-Grafts demonstrated significantly less occlusion compared to uncoated ePTFE grafts (16.8 % <i>versus</i> 29.7 %, p < 0.0005) and POC (poly(1,8-octanediol-co-citrate))-Grafts without ascorbate (16.8 % <i>versus</i> 19.9 %, p < 0.005). POCA-Grafts showed a 1.6-fold increase in endothelial cell coverage and significantly reduced leukocyte and macrophage infiltration compared to uncoated ePTFE grafts, particularly in female animals. These results suggest that the POCA coating enhances graft biocompatibility by promoting endothelialization and reducing inflammation, thereby inhibiting neointimal hyperplasia and improving graft patency. Overall, these results highlight the therapeutic potential of an ascorbate-functionalized poly(diol-co-citrate) elastomer for vascular applications and support future evaluation in large animal models.