Research On Antithrombogenic And Endothelialization Of Ti-(Ta)-O Film

The biomaterials and artificial implanted prostheses or replacements are widely used in clinical cardiovascular disease treatment. However, the biocompatibility issue of the present implanted materials keep a key problem. The developments of new attractive biomaterials thus become a current major area of scientific research. In this work, titanium oxide films with doping of tantalum (Ti-(Ta)-O film) were synthesized and optimized to meet proper microstructure and characteristics, and to obtain good physical and chemical properties, fine mechanical properties, and better biocompatibility.Unbalanced magnetron sputtering was adopted to fabricate the two different series of Ti-Ta-O film to meet the challenge of enhanced properties. The composition, structure, surface morphology, and thickness of the films were investigated using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Atom force microscopy (AFM), Raman analysis, X-ray fluorescence analysis, and alpha-step profilometry, respectively. The physical and chemical properties of the Ti-Ta-O films were measured using contacting angle methods, Hall effect measurement system, and UV- spectrophotography etc. The mechanical properties of films were evaluated by microhardness measuremment and wear resistibility testing. The blood compatibility and tissue compatibility with endothelial cell of Ti-(Ta)-O films were emphatically investigated by in vitro testing system and in vivo implanted animal experiment, including platelet adhesion test, the evaluation of biological behavior of cultured human umbilical vein endothelial cells (HUVEC), investigation of the vascular stent and valve coated by Ti-(Ta)-O film by implanting into the ventral aorta of the rabbit and right auricle of the dog, respectively. The study further attempted experimentally to modify the films surface by biochemical method for improving the endothelialization of Ti-(Ta)-O film surafce. Morever, The preliminary mechanism based on the relationship between the characteristics of materials and biological properties of films was further discussed.The micro- characteristics analysis of Ti-Ta-O films showed that the film was consist of several different titanium oxide phase except tantalum oxide. The tantalum content of films were different with from the designed sputtering target. The surface morphology of different Ti-Ta-O films were dissimilar owing to the different Ta density, and the high Ta content film surface was smoother.The results of physical and chemical properties measurement of Ti-Ta-O films revealed that, the wettability, the surface energy, the interfacial tension, and the electrical resistance of Ti-Ta-O films were changed due to the doping of Ta element. However, the semiconductivity with n type of the films was uninfluenced by Ta content, and the band gap of Ti-Ta-O films was invariably 3.2 eV. In addition, the study results disclosed that the mechanical properties of Ti-Ta-O films could be improved with proper Ta element content in films.A number of blood compatibility investigation results displayed that the optimized Ti-Ta-O film with appropriate characteristics and proper Ta content possessed excellent hemocompatibility. No obvious hemolytic reaction, platelet activation and coagulation factors activation were existed onto optimized Ti-Ta-O film surface contacting with blood. At the same time, the results of measured clotting time and of adhered protein amount indicated that the antithrombogenic ability of optimized Ti-(Ta)-O film was much better than that of low temperature isotropic pyrolytic carbon (LTIC). Morever, the thromboresistance of above films was still good while implanted the animal body.The evaluation results of endothelial cells (ECs) cultured onto film surface enunciated that the biological behavior of ECs on different Ti-(Ta)-O film surface was significant different. The biological behaviors of ECs were greatly effected by structure, composite and surface morphology of the films. The adherence, growth and proliferation of ECs are very excellent onto Ti-(Ta)-O film surface with crystalline, proper ratio of oxide to titanium, appropriate Ta content and suitable surface roughness. Furthermore, the in vivo investigation results further testified that the endothelial cells could growth with a normal shape of monolayer and slabstone collocation onto Ti-(Ta)-O film surface implanted the animal body for 5 months. The ECs on film surface could be key factors contributing to the hemocompatibility.It is believed that seeding with endothelial cells on vascular prostheses may overcome thrombus problem because of non-thrombogenic properties of the cells in nature state in contacting with blood. Therefore endothelialization of cardiovascular devices surface has been regard as an important mean to obtain good antithrombogenic biofunctionality surface. The results of the biochemical modification of Ti-(Ta)-O film surface suggested that the immobilization of biomacromolecule could enhance endothelial cell adhesion.The materials characteristics such as micro- characteristics, surface energy, critical surface tension, and semiconductivity play important roles for its good biocompatibility. The study indicated that Ti-(Ta)-O film surface with proper characteristics was helpful for blood compatibility and seeding endothelial cells, which supplied a natural biocompatible substrate.As a result, the optimized Ti-(Ta)-O film exhibit good mechanical properties, good blood compatibility exceeding that of LTIC, and attractive tissue compatibility with endothelial cell. So, this research suggest that the biocompatible Ti-(Ta)-O film is potentially useful in commercial biomedical applications such as artificial heart valves and stents.