Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs

We first identified thrombomodulin (TM) and endothelial nitric oxide (NO) synthase as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Then, recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug were immobilized on the surface of the vascular grafts. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts. Importantly, we found that the combination of TM and NO also promoted endothelialization, whereas it reduced adverse intimal hyperplasia, which is critical for the maintenance of vascular homeostasis, as confirmed in rat and pig models.