Tyrosinase-Mediated Surface Coimmobilization of Heparin and Silver Nanoparticles for Antithrombotic and Antimicrobial Activities

Thrombus and infections are the most common causes for the failure of medical devices, leading to higher hospitalization costs and, in some cases, patient morbidity. It is, therefore, necessary to develop novel strategies to prevent thrombosis and infection caused by medical devices. Herein, we report a simple and a highly efficient strategy to impart antithrombotic and antimicrobial properties to substrates, by simultaneously immobilizing heparin and in situ-synthesized silver nanoparticles (Ag NPs) via a tyrosinase-catalyzed reaction. This consists of tyrosinase-oxidized phenolic groups of a heparin derivative (heparin-grafted tyramine, HT) to catechol groups, followed by immobilizing heparin and inducing the in situ Ag NP formation onto poly(urethane) (PU) substrates. The successful immobilization of both heparin and in situ Ag NPs on the substrates was confirmed by analyses of water contact angles, XPS, SEM, and AFM. The sustained silver release and the surface stability were observed for 30 days. Importantly, the antithrombotic potential of the immobilized surfaces was demonstrated by a reduction in fibrinogen absorption, platelet adhesion, and prolonged blood clotting time. Additionally, the modified PU substrates also exhibited remarkable antibacterial properties against both Gram-positive and Gram-negative bacteria. The results of this work suggest a useful, effective, and time-saving method to improve simultaneous antithrombotic and antibacterial performances of a variety of substrate materials for medical devices.