Multifunctional surfaces through synergistic effects of heparin and nitric oxide release for a highly efficient treatment of blood-contacting devices

Abstract

Thrombosis and inflammation after implantation remain unsolved problems associated with various medical devices with blood-contacting applications. In this study, we develop a multifunctional biomaterial with enhanced hemocompatibility and anti-inflammatory effects by combining the anticoagulant activity of heparin with the vasodilatory and anti-inflammatory properties of nitric oxide (NO). The co-immobilization of these two key molecules with distinct therapeutic effects is achieved by simultaneous conjugation of heparin (HT) and copper nanoparticles (Cu NPs), an NO-generating catalyst, via a simple tyrosinase (Tyr)-mediated reaction. The resulting immobilized surface showed long-term, stable and adjustable NO release for 14 days. Importantly, the makeup of the material endows the surface with the ability to promote endothelialization and to inhibit coagulation, platelet activation and smooth muscle cell proliferation. In addition, the HT/Cu NP co-immobilized surface enhanced macrophage polarization towards the M2 phenotype in vitro, which can reduce the inflammatory response and improve the adaptation of implants in vivo. This study demonstrated a simple but efficient method of developing a multifunctional surface for blood-contacting devices.

Keywords: Anti-inflammation; Antithrombosis; Blood-contacting devices; Heparin; Nitric oxide; Tyrosinase.