基于共价固定高密度透明质酸构建具有抗菌抗凝血双功能的表面

Construction of Surface with Anticoagulant and Antibacterial Functions via a Covalent Immobilization of Hyaluronic Acid with High Density

表面血栓生成和细菌感染是导致体外血液循环装置及留置器械等血液接触类器材失效的重要原因,表面接枝生物活性分子是赋予材料表面抗血栓及抗菌性能的重要手段。然而,现有的抗菌抗凝血双功能改性方法通常基于复杂的改性策略并难以良好地整合抗菌抗凝血的效能,如普遍使用的含银抗菌策略对血液抗凝并不友好。因此,利用简单接枝生物分子同时提高血液接触材料的抗菌抗凝血性能具有很大的挑战和意义。本研究将透明质酸(HA)分子高密度地接枝在氨基化表面,利用透明质酸的高度水合能力和除污特性,赋予了材料表面有效的抗菌与抗凝血功能。本策略首先将聚烯丙胺(PAa)在碱性条件下以席夫碱反应和迈克尔加成方式接枝在聚多巴胺(PDA)涂层表面,从而构建出富氨基涂层(PADA)。进一步通过酰胺化反应将HA共价固定在PADA表面,得到功能化涂层(HA-PADA)。衰减全反射傅里叶变换红外光谱(ATR-FTIR)和X射线光电子能谱(XPS)结果证实成功制备了HA-PADA涂层。体外纤维蛋白原和血小板的粘附激活实验以及抗菌实验的结果验证了HA-PADA涂层可以显著抑制凝血和细菌粘附。因此,该方法构建的具有高HA密度且稳定的HA-PADA双功能涂层对于提高血液接触类器材表面的血液相容性和抗菌性能具有很好的参考意义。

Thrombosis and infections are the two major clinical complications that lead to the failure of blood-contacting biomaterials,such as in vitro blood circulation and indwelling devices.Grafting of bio-functional molecules is one of the important methods for surface modification of biomaterials.However,existing methods to solve these two complications are often based on complex modification strategies and a series of adverse reactions,for example,the commonly used silver-containing antibacterial strategy exhibits undesired hemocompatibility.Therefore,improving the antibacterial and anticoagulant properties of blood-contacting materials by simply grafting biomolecules is challenging and significant.In this study,poly(allylamine)(PAa)modified poly(dopamine)(PDA)through Schiff alkali reaction and Michael addition in alkaline condition to construct a rich-amine coating(PADA).HA was covalently immobilized to PADA based on amine coupling.The functional coating(HA-PADA)obtained both anticoagulant and antibacterial properties due to the water binding capacity and antifouling property of HA.The successful preparation of the HA-PADA coating was confirmed by attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR)and X-ray photoelectron spectroscopy(XPS).The results of the adhesion and activation of fibrinogen and platelets and the antibacterial test on the surfaces confirmed that the HA-PADA coatings can significantly inhibit coagulation and bacterial adhesion.We anticipate that the dual-functional HA-PADA coating strategy with stable and ultra-high HA density would be a milestone in the development of surface engineering,especially to that of blood-contacting biomedical devices.