【作者】 逯平；

【导师】 许鑫华；

【作者基本信息】 天津大学 ， 材料学， 2009， 博士

【摘要】 镁合金因其优良的机械性能和生物可吸收性,被认为是潜在的血管支架材料,然而高的腐蚀速率限制了镁合金的医学应用,降解速率过快会使支架的机械力学性能下降;较高浓度的腐蚀产物人体产生毒副作用;同时腐蚀产物的脱落易堵塞血管,形成血栓,腐蚀速度过快会导致支架的再狭窄,因此提高镁合金耐腐蚀至关重要。本文在镁合金表面制备具有防腐与药物释放双重可控性能的复合涂层,研究其耐腐蚀性能、药物释放行为及生物相容性。本文采用微弧氧化(MAO)并封孔的方法在WE42及AZ81镁合金表面制备耐腐蚀性陶瓷膜,通过控制微弧氧化电流密度来控制MAO膜的耐腐蚀性大小;采用聚左旋乳酸(PLLA)及化学镀膜封孔MAO膜表面的微孔与裂纹。SEM表明复合膜致密规则且无表面缺陷,有效填充了微弧氧化表面裂纹,XRD及EDS表征膜层相成分及元素组成,电化学实验及浸泡实验表明MAO封孔后镁合金耐腐蚀阻抗提高,镁离子释放速率下降;血液相容性实验表明MAO/PLLA改性后的镁合金具有较低的溶血率及较好的抗凝血性,细胞毒性级别均为1级,且未产生急性与亚急性中毒,表明样品具有良好的生物相容性。为了减少支架植入后的再狭窄,在支架耐腐蚀性涂层表面制备药物控释膜。采用生物相容性好的PLGA(PTX)作为药物释放膜,采用交联明胶及空白PLGA作为药物控释层。药物释放膜的差示扫描(DSC)与红外光谱(FTIR)分析表明紫杉醇(PTX)以分子状态分散于聚乳酸乙醇酸共聚物(PLGA)中,提高明胶交联度及LA:GA配比可以减少药物突释,使药物保持持续缓慢更长时间的释放,而增加PEG含量与PEG相对分子质量则提高药物释放率,因此达到对药物的控制释放。采用交联明胶/PLGA载药微球复合膜封孔微弧氧化膜,SEM与AFM表明载药微球光滑致密无粘连;这层复合膜不仅可以封孔MAO膜表面的微孔与裂纹提高镁合金的腐蚀阻抗,同时携带PLGA(PTX)载药微球,而且降低了膜层数目,提高明胶交联度,药物突释明显减少药物释放率降低,且镁合金的腐蚀阻抗提高,因此达到镁合金支架防腐与药物释放双重可控。更多还原

【Abstract】 Magnesium alloys may potentially be applied as vascular stent materials due to their good mechanical properties and bioabsorbility. However, the high corrosion rate hinders its clinical application. Due to the rapid biodegradation of the magnesium alloy stents, the mechanical properties of the stents would be lost and high concentration of the corrosion products would produce toxic side effects on the human body. In addition, the corrosion products will block the vessels and form the thrombosis. High corrosion rate could cause in-stent restenosis, so it is very important to improve the anticorrosion resistance of the magnesium alloy stents. In this paper, a composite film which could double controlled anticorrosion and drug release behavior was fabricated on the magnesium alloy WE42 and AZ81 which were used as vascular stent materials and the anticorrosion resistance、drug release behavior and biocompatibility were demonstrated.In this research, an anticorrosion ceramic film was fabricated on the surface of magnesium alloy WE42 and AZ81 by micro-arc oxidation (MAO) and sealing method. The anticorrosion resistance could be controlled by the adjustment of the current density. The Poly-L-Lactide acid(PLLA) and electroless nickel plating was used to seal the microholes and microcracks on the surface of the MAO coating. X-ray powder diffraction (XRD) and energy spectrum analysis (EDS) could anal size the phase composition and elements of the MAO coating. Electrochemical measurements and the immersion tests showed the anticorrosion resistance of the WE42 modified with composite coating increased and the release rate of magnesium ions decreased. Hemocompatibility tests showed that the magnesium alloy after MAO/PLLA modified had lower hemolysis rate and good anticoagulant properties. The rank of the cytotoxic levels was one, and the acute toxicity and subacute toxicity not were happen. It showed the samples had good biocompatibility.In order to decrease the in-stent restenosis rate, drug controlled release films were fabricated on the surface of the anticorrosion coating of the stents. Biocompatibility PLGA(PTX) film was used as drug release film and the top crosslinked gelatin and blank PLGA film was used to control the drug release rate. Differential scanning calorimetry (DSC) test and Fourier transformation infrared rays (FTIR) showed the paclitaxel(PTX) was dispersed well in a molecular dispersive state in poly(DL-lactide-co-glycolide) (PLGA) matrix. When the cross linked degree of the gelatin increased, the drug release could keep sustained-release for a longer time with no significant the burst release. When the content and the molecular weight of the PEG increased, the drug release rate could be controlled.Cross linked gelatin(PLGA NPs) composite coating was used to seal the MAO coating. SEM and atomic force microscopy (AFM) showed that the nanoparticles(NPs) was smooth and compact with no aggregation or adhesion. This composite coating could not only improve the corrosion resistance by sealing the microcracks and microholes on the surface of the MAO coating, but also release drug by carrying PLGA(PTX) nanoparticles. Otherwise, this composite film could decrease the numbers of the films. The result showed that when the cross linked degree of the gelatin increased that the drug release rate would decrease with no significant burst releases. Also, when the cross linked degree of the gelatin increased, the anticorrosion resistance would increase. All these results showed the magnesium alloy could double control the anticorrosion and drug release by surface modification.更多还原