ObjectiveImplantation of an endovascular device disrupts the homeostatic CD31:CD31 interactions among quiescent endothelial cells, platelets, and circulating leukocytes. The aim of this study was to design an endothelial-mimetic coating of nitinol and cobalt-chromium (CoCr) surfaces and stents using synthetic CD31 peptides, to promote device endothelialization and pacific integration within the arterial wall. MethodsPeptides mimicking the domains 1 and 2 of CD31 were synthetized and immobilized onto experimental nitinol and cobalt chromium (CoCr) surfaces using a three-step dip-coating, mussel-inspired protocol using copper-free click chemistry. Human aortic endothelial cells (HAEC, Lonza) phenotype and endothelialization assessment using parallel scratch tests were carried out using five synthetic CD31 peptides coated on 4.8 mm nitinol and CoCr flat disks, and were compared to control disks. The CD31 peptide exhibiting the best results in vitro was then immobilized on clinical-grade 3 x 40 mm self-expanding nitinol and 2.5 x 20 mm balloon-expandable CoCr stents (Sino Medical Sciences Technology Inc., Tianjin, China). Such devices were implanted in native arteries of White New Zealand rabbits, and compared to control uncoated bare-metal stents (BMS) and drug-eluting stents (DES) 7 and 30 days after implantation using resin cross-sections and scanning electron microscopy (n = 2-3 / group / time point). ResultsMembrane-distal CD31 domains 1 and 2 peptides exhibited a distinct capability to foster a healthy endothelial phenotype and to promote endothelialization in vitro. By day 7 post-implantation, CD31 nitinol and CoCr stents were evenly covered by wholesome endothelial cells, devoid of thrombo-inflammatory signs, in contrast to both BMS and DES. Such results were consistent until day 30. ConclusionMembrane-distal CD31 biomimetic peptides seem to effectively camouflage the device surface, preventing local reactions and promoting rapid and seamless endovascular integration.