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Atherosclerotic vascular disease, in the form of coronary artery and peripheral vascular disease, remains the leading cause of mortality in the United States.[1] For many patients, suitable vein autografts are not available.[2] Synthetic grafts made from Dacron (polyethylene terephthalate) or expanded polytetrafluoroethylene (ePTFE) are mostly used in large-diameter (> 6 mm inner diameter) blood-vessel applications. However, their use in small-diameter blood vessels has been fraught with poor patency due to early graft occlusion from thrombosis.[3, 4] Surface-modification protocols mostly target ePTFE vascular grafts, the current standard-of-care, as their innate surface is thrombogenic and their intrinsic hydrophobicity can limit endothelium formation.[3, 5–8] Modifications to improve the thromboresistance of the graft have focused on the coating or immobilization of biomacromolecules or nondegradable polymers to promote endothelialization of the graft’s lumen.[6, 9–19] However, concerns regarding changes to the graft’s compliance, host responses to the coating material, transmission of pathogens, high costs, and long-term patency still remain.[3, 20] To date, no one has investigated the use of synthetic biodegradable polymers as a means to tissue-engineer a functional endothelium on ePTFE grafts. We demonstrate that the biodegradable elastomer poly (1, 8-octanediol citrate)(POC) can confer improved biocompatibility characteristics on ePTFE vascular grafts without affecting graft compliance. The approach ultimately aims to improve early thromboresistance and perhaps inhibit neointimal hyperplasia by promoting POC-mediated …