Poly(2-methoxyethyl acrylate) analog coatings enhance long-term endothelialization and support blood-compatible healing of vascular grafts in nonhuman primate models

Complete tissue healing of a vascular graft is characterized by absolute endothelialization of the luminal surface. Although endothelial cells frequently appear at anastomotic sites, they are rarely detected on the luminal surface even years after implantation. This issue is pronounced in small-diameter grafts where endothelialization is crucial for long-term patency. Various approaches, such as tissue-engineered autologous vessels, have been explored to promote early endothelialization, but commercialization remains limited owing to cost and complexity. We evaluated the effects of alternative poly(2-methoxyethyl acrylate) (PMEA, QA) and the related polymers poly(3-methoxypropyl acrylate) (PMC3A, QB), poly(2-(2-ethoxyethoxy)ethyl methacrylate) (PEt2MA, QC), and poly(6-methoxyhexyl acrylate) (PMC6A, QD) materials in vitro on platelet adhesion under dynamic conditions and human umbilical vein endothelial cell (HUVEC) attachment under static conditions. All these materials had antiplatelet properties and promoted endothelial cell attachment and proliferation. We coated them onto vascular grafts and then implanted them in monkeys in vivo. Significant thrombus formation was undetectable at 4 weeks, which was consistent with the findings in vitro. The endothelial coverage of polymer QC was notably >90% at 26 and 52 weeks, which strongly correlated with the HUVEC attachment results in vitro. These polymers also healed tissues more effectively than the control material (Gelweave®). These findings underscore the predictive value of in vitro dynamic assays for in vivo graft performance and the promise of PMEA analog coatings as candidates for next-generation vascular grafts with improved long-term biocompatibility.