RESUMEN
Introducing antifouling property to biomaterial surfaces has been considered an effective method for preventing the failure of implanted devices. In order to achieve this, the immobilization of zwitterions on biomaterial surfaces has been proven to be an excellent way of improving anti-adhesive potency. In this study, poly(sulfobetaine-co-tyramine), a tyramine-conjugated sulfobetaine polymer, was synthesized and simply grafted onto the surface of polyurethane via a tyrosinase-mediated reaction. Surface characterization by water contact angle measurements, X-ray photoelectron spectroscopy and atomic force microscopy demonstrated that the zwitterionic polymer was successfully introduced onto the surface of polyurethane and remained stable for 7days. In vitro studies revealed that poly(sulfobetaine-co-tyramine)-coated surfaces dramatically reduced the adhesion of fibrinogen, platelets, fibroblasts, and S. aureus by over 90% in comparison with bare surfaces. These results proved that polyurethane surfaces grafted with poly(sulfobetaine-co-tyramine) via a tyrosinase-catalyzed reaction could be promising candidates for an implantable medical device with excellent bioinert abilities. STATEMENT OF SIGNIFICANCE: Antifouling surface modification is one of the key strategy to prevent the thrombus formation or infection which occurs on the surface of biomaterial after transplantation. Although there are many methods to modify the surface have been reported, necessity of simple modification technique still exists to apply for practical applications. The purpose of this study is to modify the biomaterial's surface by simply immobilizing antifouling zwitterion polymer via enzyme tyrosinase-mediated reaction which could modify versatile substrates in mild aqueous condition within fast time period. After modification, pSBTA grafted surface becomes resistant to various biological factors including proteins, cells, and bacterias. This approach appears to be a promising method to impart antifouling property on biomaterial surfaces.
Asunto(s)
Betaína/análogos & derivados , Incrustaciones Biológicas , Monofenol Monooxigenasa/metabolismo , Polímeros/química , Adsorción , Animales , Adhesión Bacteriana , Betaína/química , Materiales Biocompatibles Revestidos/química , Dihidroxifenilalanina/química , Fibrinógeno/metabolismo , Humanos , Masculino , Microscopía de Fuerza Atómica , Espectroscopía de Fotoelectrones , Adhesividad Plaquetaria , Espectroscopía de Protones por Resonancia Magnética , Ratas Sprague-Dawley , Espectrofotometría Ultravioleta , Staphylococcus aureus/citología , Tiramina/química , HumectabilidadRESUMEN
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.