【作者】 梁春永；

【导师】 杨贤金；

【作者基本信息】 天津大学 ， 材料学， 2008， 博士

【摘要】 钛及其合金因其优异性能已越来越多的被应用于临床医学。表面改性是目前解决合金在医学领域应用的主要障碍的有效途径,其原因主要有两个方面,其一是将植入材料进行表面图案化,以改变材料表面形貌和提高表面粗糙度,从而提高骨组织与植入材料的机械锁合力和结合强度;其二是在金属表面制备生物强化层或活性层,来改善材料的生物活性,以提高骨组织与材料的结合力,同时减少基体材料中有害离子的溶出,降低材料的生物毒性。本文采用飞秒激光和喷砂后酸蚀工艺在Ti及其合金表面加工不同显微图案结构。比较分析了不同图案化表面和生物活性层对生物相容性的影响,采用计算机技术模拟了HA在样品表面的生长过程,制定合理的人工关节和骨修复器表面生物活化层制备工艺。主要研究结果表明:喷砂工艺能有效提高样品的表面粗糙度。当砂粒尺寸为150目时,得到了既满足精度要求又具有较大生物活性的样品表面。喷砂后的样品先经草酸处理再进行硝酸氧化的方法能够既有效去除表面污染,又能获得良好的氧化层,从而提高基体的生物相容性。采用飞秒激光在NiTi合金及纯Ti为基的样品上加工不同周期结构图案。仿生生长HA的实验表明,在这种具有多级拓扑结构并具有Ti氧化层的表面,HA的生长速度要高于在喷砂酸蚀处理的表面。通过体外实验比较不同的图案化表面和有无类骨磷灰石Ti合金表面对成骨细胞生长数量和形态的影响。MTT测试表明,经飞秒激光及喷砂酸蚀表面图案化处理的试样上细胞增殖总数及增殖速率均大于未处理试样,且样品表面的图案结构有利于诱导细胞生长更多的伪足,使其按图案化结构定向攀附,从而提高细胞的贴附生长能力。Ti合金表面生长类骨磷灰石层能有效屏蔽有害离子的溶出,从而显著提高细胞增殖速率。与仅经图案化处理的样品相比,仿生生长HA活性层的样品诱导细胞分泌ALP的能力更强,有利于Ca²⁺的矿化沉积。根据第一性原理对溶液中各种离子在羟基化的TiO₂表面的沉积进行了模拟,分析羟基磷灰石的动态生长过程。结果表明,在反应的初始阶段,溶液中的PO43-首先与水反应生成H₂PO4-,H₂PO4-将诱导至羟基化的TiO₂表面。然后H₂PO4-离出的H+与TiO₂表面的OH-结合形成水分子进入溶液,从而引起溶液中PO43-的沉积。为保持溶液的电中性,沉积PO43-后的表面将吸附Ca²⁺,并诱导了Ca²⁺的沉积,计算结果表明,Ca²⁺将优先在PO43-与TiO₂表面形成的八面体间隙位置沉积。随着反应的不断进行,最终在TiO₂表面形成以化学方式结合的钙磷层。根据理论研究和前期试验结果,提出最终的在骨修复器件表面制备生物活化层的方案,采用自制设备在商用钛合金人工关节和骨修复器表面制备出均匀活性层,所处理的商用钛合金植入体尺寸精度符合植入要求。并进行了动物体内试验。体内试验表明,经喷砂加酸蚀预处理结合仿生化学法制备类骨磷灰石新工艺表面处理后的植入体,更有利于成骨细胞的生长矿化,加速骨的传导和生长过程,能够迅速与骨组织形成无缝隙的骨性结合。更多还原

【Abstract】 Ti and Ti alloys have been applied to clinical medicine for their excellent properties. Surface modification is an efficient method to eliminate the restriction in medical applications for Ti alloys. For the surface modification, two aspects should be considered: one is the patterned surface of implant, which can modify the surface appearance and roughness, then improve the mechanical locking force and boning strength between the osseous tissue and the implant; another is the preparation of active layer on the metal surface, which can improve the bioactivity of implant and the binding force, depress the release of noxious ionic, and decrese the cytotoxity of the materials.In the present work,femtosecond laser technology （FLT） and sand blasting followed by acid treatment treatment （SLA） were used to prepare the pattern surface of Ti and Ti alloys. The effects of pattern surface and bioactivity layer on biocompatibility were investigated by compartion analysis, and hydroxyaptite （HA） growing process on the specimen with various pattern surfaces was simulated. Furthermore uniform bioactivity layer was prepared on medical implants. The research results show that SLA can effectively improve the surface roughness of specimen. When the sand grain size is 150#, the specimen surface is satisfied for the accuracy requirement and exhibits good bioactivity. The oxalic acid by nitric acid oxidation treatment after sand blasting can eliminate the surface contamination. Meanwhile, the favorable oxide layer is formed, which can improve the biocompatibility.The pattens on the NiTi and Ti with different periodic structures were fabricated by FLT. The experiments show that the growthing rate of HA layer on the Ti oxide layer with multiplevel topology structure is faster than that on the surface treated by SLA.The vitro experiments were used to investigate the influence of Ti alloy surface with different pattern on the quantity and shape of osteoblast. The influence of Ti alloy surface with or without bone-like apatite was also studied using same method. MTT （3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide） reduction assay shows that the cell multiplication quantity and multiplication rate on the pattern surface subjected to FLT and SLA are greater than those on the untreated surface. Moreover, the pattern structure favor to induce the growth of cell pseudopod, which can speel directionally along the pattern microstucture. Therefore, the ability of cell anchorage growth is improved. The HA layer on the Ti alloy can depress the release of noxious ions, furthermore increase the rate of cell multiplication. As compared with the specimen only subjected to pattern treatment, the specimen with bionic growth HA layer has better ability for indcucing the alkaline phosphatase secretion, which is in favor of the mineralize precipitation of Ca²⁺.According to the first principles,the deposition processs of different ions in solution on the hydroxylating TiO₂ surface were simulated by a computer to analyze the HA dynamic growth process. The results show: the PO43- reacts with H₂O to form H₂PO4- group, and the H₂ PO4- group deposites on the hydroxylating TiO₂ surface at the initial stage. And then, the H+ in the H₂PO4- group separates out and combined with OH- on the TiO₂ surface to form H₂O. This would result in the acumulation of PO43- group in the solution. To keep the electroneutrality of solution, the alloy surface would absorb the Ca²⁺ to form the precipitation of Ca²⁺group. The results of computer simulation show that the Ca²⁺group deposits at the octahedral interstices sites of the PO43- group and TiO₂ surface. With further reaction, the calcium phosphorus layer with chemical combination mode would be form on the TiO₂ surface.According to the theroretical investingation and experimental results, the method to prepare bioactivity layer on medical implants （artificial joints and bone restoring body） was established, and the layer, which were prepared by special equipment, are homogenous. The dimensional accuracy of the implants subjected to treatment can meet the demand of implantations. The vivo-tests were also carried out. The results show that the implants subjected to the surface treatment combining the acid erosion after sandblasting and biomimetic chemistry growthing HA layer are favourable to the growth mineralization of osteoblast, which accelerates osseous conduction, bone growth and the formation of seamless synostosis with osseous tissue.更多还原