【作者】 刘颖；

【导师】 张二林；

【作者基本信息】 东北大学 ， 材料学， 2019， 硕士

【摘要】 生物医用钴基合金以其良好的耐磨性能、耐蚀性能以及优良的生物相容性而被广泛应用于生物医用领域,尤其是髋关节、膝关节等硬质生物体置换物。前期研究发现,铸态CoCrMo合金中加入少量的抗菌铜元素可以降低细菌感染风险。然而金属材料在植入后,服役于复杂的生理环境中,再加上人体行为活动,容易引起金属离子释放及材料磨损损伤等问题造成植入材料性质发生改变,导致植入失效。同时植入材料易与生物体发生反应造成宿主细胞功能损坏或死亡,对材料长期安全使用及人体健康造成严重威胁。本文选择铜元素作为抗菌剂,利用扫描电子显微镜研究了铜含量不同的抗菌CoCrMo-Cu合金的微观组织;利用电化学工作站和摩擦磨损试验机分析了合金在不同模拟体液环境中的耐蚀性能、耐磨性能及其互相作用;通过细胞形态观察及CCK-8检测研究了铜离子浓度以及含铜钴合金对成骨细胞的毒性作用并通过RT-PCR法研究了成骨相关基因(OCN,COL-I)的表达。主要研究结果如下:微观组织观察结果表明,在CoCrMo,CoCrMo-2Cu以及CoCrMo-4Cu三种铸态合金中均存在不规则状的碳化物和金属间化合物两种第二相,在CoCrMo-2Cu合金中,铜元素主要以固溶形式存在于基体中,而CoCrMo-4Cu合金在第二相与基体交界处有明显的富铜相存在。电化学实验结果表明,铜的加入会略微增大材料在模拟体液中的自腐蚀电流密度,降低合金的耐蚀性能,但三种合金间相差不大。耐磨实验结果表明,含铜钴合金的耐磨性能低于CoCrMo合金,在含有胎牛血清的细胞培养基中的三种合金的磨损率均明显降低。通过比较外加不同恒电位情况下合金的磨损体积可以发现,恒电位越大时,合金的总磨损体积越大,但由磨损造成的体积损失仍占主导作用,腐蚀造成的损失占次要作用。通过检测细胞毒性及成骨相关基因表达水平发现,当培养基中铜离子浓度处于1×10-4 mol/L～1×10-6 mol/L范围内,细胞呈菱形、长梭形铺展于培养板中,生长状态良好,当铜离子浓度达到1×10-3 mol/L时,细胞呈圆球状,漂浮于培养基中,细胞全部死亡。低浓度的铜离子对细胞成骨基因表达有促进作用,其中以铜离子浓度为1×10-6 mol/L最为明显。与空白对照组相比,三种钴合金表面的细胞生长状态良好,细胞相对增值率均能达到85%以上,且成骨细胞OCN与COL-I基因表达量均能达到80%以上,表明合金具有良好的细胞相容性。更多还原

【Abstract】 Biomedical cobalt-based alloys are widely used in the biomedical field due to their good wear resistance,corrosion resistance and excellent biocompatibility,especially for hard organism replacements such as joints and dentures.Previous studies have found that the addition of a small amount of antibacterial copper in the as-cast CoCrMo alloy could reduce the risk of bacterial infection during replacement surgery.However,due to the complex physiological environment coupled with artificial behavioral movements,the metal material implanted would cause metal ion released,material wear damaged and other problems,which can result in changing the implant material properties,or even implantation failure.Furthermore,implanted materials are easy to react with the body,causing cytotoxicity,and seriously threatening the long-term safe use of implanted materials and human health.In this paper,Cu element was selected as an antibacterial agent.The effect of copper addition and its content on the microstructure of antibacterial CoCrMo-Cu alloy was investigated by scanning electron microscopy.The corrosion and wear properties of the alloys were studied by electrochemical workstation and wear tester.The toxicity of copper ions and alloys to MC3T3-E1 was analyzed by morphological observation and CCK-8 method.The expression of osteogenic related genes(OCN,COL-I)was studied by Real-Time PCR.The main results are summarized as follows:Microstructure observation results showed that two kinds of second phase distributions of carbides and intermetallic compounds with obvious irregular shapes in CoCrMo,CoCrMo-2Cu and CoCrMo-4Cu alloys.In CoCrMo-2Cu alloys,copper mainly existed in the matrix in the form of solid solution while the CoCrMo-4Cu alloy had a distinct copper-rich phase at the junction of the second phase and the matrix.The results of corrosion resistance showed that the addition of copper element could slightly increase the self-corrosive current density of materials in simulated solution and reduce the corrosion resistance of the alloy,but the difference was not significant.The results of wear resistance test showed that the wear resistance of alloys with Cu added was lower than CoCrMo alloy.In addition,the wear rate of the alloy in the cell culture medium containing fetal bovine serum was significantly reduced.Compared with the wear rates of alloys with different potentiostatic,it could be found that the larger the potentiostatic was,the higher the total wear volume of the alloys would be,but the volume loss caused by wear still played a dominant role,and the loss caused by corrosion played a secondary role.By detecting the cytotoxicity and osteogenesis related gene expression level,it was found that when the copper ions concentration in the range of 1×10-4 mol/L～1×10-6 mol/L,the cells spreaded out in the culture plate in a rhombic and long spindle shape.They grew well.When the concentration of copper ion reached 1×10-3 Hol/L,all the cells died and floated in the cell culture medium in a spherical shape Besides,the concentration of copper ions at low concentration promoted the expression of osteogenic genes in cells,with 1×10-6 mol/L being the most obvious.Compared with the blank control group,the cells on the surface of the CoCrMo-Cu alloys grew well,and the relative growth rate of the cells reached more than 85%,and the expression of OCN and COL-I genes reached more than 80%,which indicated that the alloys had good cell compatibility.更多还原