To improve the blood compatibility and endothelialization simultaneously and to ensure the long-term effectiveness of the cardiovascular implants, we developed a surface modification method, enabling the coimmobilization of biomolecules to metal surfaces. In the present study, a heparin and fibronectin mixture (Hep/Fn) covalently immobilized on a titanium (Ti) substrate for biocompatibility was investigated. Different systems [N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and N-hydroxysuccinimide, electrostatic] were used for the formation of Hep/Fn layers. Atomic force microscopy (AFM) showed that the roughness of the silanized Ti surface decreased after the immobilization of Hep/Fn. Fourier transform infrared spectroscopy (FTIR), Toluidine Blue O (TBO) test, and immunochemistry assay showed that Hep/Fn mixture was successfully immobilized on Ti surface. Blood compatibility tests (hemolysis rate, APTT, platelet adhesion, fibrinogen conformational change) showed that the coimmobilized films of Hep/Fn mixture reduced blood hemolysis rate, prolonged blood coagulation time, reduced platelets activation and aggregation, and induced less fibrinogen conformational change compared with a bare Ti surface. Endothelial cell (EC) seeding showed more EC with better morphology on pH 4 samples than on pH 7 and EDC/NHS samples, which showed rounded and aggregated cells. Systematic evaluation showed that the pH 4 samples also had much better blood compatibility. All results suggest that the coimmobilized films of Hep/Fn can confer excellent antithrombotic properties and with good endothelialization. We envisage that this method will provide a potential and effective solution for the surface modification of cardiovascular implant materials.

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Recently, UV irradiation has been reported as a new approach to significantly improve the anticoagulant properties of titanium dioxide (TiO2) films by suppressing fibrinogen adsorption and platelet adhesion. This study focuses on how fibrinogen adsorption of and platelet adhesion to TiO2 films is affected by the duration of UV irradiation. Furthermore, this study intends to describe the link between the suppression effect and the changes in the TiO2 films nature caused by photogenerated reactive oxygen species (ROS). First, we performed UV irradiation in different atmospheres as model 1 to determine the effect of oxygen gas on the anticoagulant properties of TiO2 films. The results showed that the suppression of platelet adhesion induced by UV irradiation depended on the presence of oxygen gas, indicating that ROS were photogenerated, and the ROS-induced surface change was related to the improvement in the anticoagulant ability. Then, we fabricated three other types of TiO2 samples in air by varying the UV irradiation time: (1) model 2, comprising fully UV-irradiated TiO2 films, (2) model 3, comprising partially UV-irradiated TiO2 films, and (3) model 4, comprising fully UV-irradiated TiO2-Si micropatterns. The results indicated that UV irradiation affected the anticoagulant properties of TiO2 films in a time-dependent manner. UV irradiation on TiO2 films for short duration (e.g., 1 min) evidenced a suppression effect on fibrinogen adsorption and platelet adhesion, an effect that could not be the result of photoinduced superhydrophilicity, increased hydroxyl groups (-OH) number, or decomposition of the adsorbed hydrocarbon. When the UV irradiation time was longer, this suppression effect extended from the surface of the UV-irradiated TiO2 films to the surface of the adjacent masked TiO2 films and the nearby Si surface. This result supported that the suppression effect could be related to the changes in the nature of the TiO2 films that were caused by the photogenerated and diffused ROS. Further, this extension of the suppression effect to the Si surface indicated that the photogenerated ROS could be used to improve the anticoagulant properties of other materials. A prolonged UV irradiation time (e.g., 240 min) may enhance the fibrinogen adsorption of and platelet adhesion to TiO2 films, which could be related to the decomposition of the adsorbed hydrocarbon and the increase in the positive charge. However, when comparing the enhancement effect and the suppression effect, the results showed that the latter was the main one to influence fibrinogen adsorption of and platelet adhesion to TiO2 films. This study provides an important basis for understanding the behavior of UV-irradiated TiO2 films as anticoagulant materials.

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