新型含铜抗菌钛合金的制备与性能研究

发布时间：2018-09-18 17:33

【摘要】：钛合金具有良好的生物相容性、综合力学性能、机械加工性能和耐腐蚀性能,是理想的生物医用材料,被广泛用作口腔和骨科的植入材料。传统的医用钛合金属于生物惰性材料,主要起支撑作用,植入人体后容易引发细菌感染,诱发炎症反应,这种感染会反复发作,难以控制。因此,如何控制植入物术后感染是困扰医务人员的一个棘手问题,越来越受到关注。针对上述感染问题,如何保证其力学性能和耐蚀性能的前提下,使得传统广泛应用于骨科和齿科中的Ti-6Al-4V具有高效、广谱和持续的抗菌功能,并具有可靠的生物安全性,是本论文工作的主要研究目标。基于此设计思想,本研究在Ti-6Al-4V中添加适量具有抗菌功能的Cu元素,采用合适的铸、锻工艺及热处理工艺对原有合金进行优化,设计和开发出一类新型的含Cu抗菌钛合金。通过分析不同Cu含量的铸态钛合金的显微组织、力学性能、抗菌性能和耐腐蚀性能等,确定了Ti-6Al-4V-XCu的最佳Cu的添加量设计为5%。利用GLEEBLE3800热模拟试验机研究了Ti-6Al-4V-5Cu的热变形加工性能,结果显示,合金流变应力随着应变速率的升高和温度的降低而增大。经过微小的形变量,合金流变应力达到峰值后发生持续软化现象。Ti-6Al-4V-5Cu的热加工图失稳区较小,当变形温度为900-1050。C,应变速率为0.001-0.1 s-1时,功率耗散因子达到0.48,在此条件下合金易发生动态再结晶,热变形最安全。获得了Ti-6Al-4V-5Cu热变形时的本构方程：ε=6.700×1012[sinh (0.014σ)]2.809exp (-320×103/RT)σ=71.4291n{(Z/6.700×1012)1/2809+[(Z/6.700×1012)2/2.809+1]1/2}Ti-6Al-4V-5Cu材料经锻造加工及热处理分析后,根据不同热处理对应的组织结构及性能分析,得出Ti-6Al-4V-5Cu综合性能最佳的热处理制度为加热930。C水淬+600℃时效空冷。通过对Ti-6Al-4V-5Cu的Cu的分布规律及溶出机制研究,探讨了组织结构对合金主要抗菌相Cu2+离子溶出及对抗菌性能的影响机理。研究结果表明,Cu元素在Ti-6Al-4V-5Cu中主要以固溶态和金属间化合物Ti2Cu两种形式存在于a相与p相。由于金属间化合物的化学稳定性更强,因此,Cu2+离子更容易以固溶态形式溶出。另外,Cu在合金p相中的溶解度大于α相,热处理可改变α/β相比例从而改变Cu在合金中的分布。当合金中的p相增多时,合金中Cu的分布均匀弥散,Cu2+离子更容易均匀溶出,从而增强合金的抗菌性能。采用覆膜法、表面形貌观察和荧光染色法考察了Ti-6Al-4V-5Cu的抗菌性能,测定了Cu2+离子梯度浓度对金黄色葡萄球菌的抑制作用,通过EMA-PCR、基因检测等分子学水平定量实验揭示了Cu2+离子的抗菌机制。结果表明,Ti-6Al-4V-5Cu对大肠杆菌和金黄色葡萄球菌有强烈的杀灭作用,能有效抑制细菌生物膜的形成,Cu2+离子对金黄色葡萄球菌的最小抑菌浓度为100μg/L。Ti-6Al-4V-5Cu的抗菌机制是：当合金与菌液接触后,微量的Cu2+离子从合金中溶出,浓度梯度驱动Cu2+离子从合金表面扩散到细菌液中,与细菌接触破坏细菌外层的细菌膜,增大细菌膜的通透性,导致细菌中的蛋白质和还原糖等渗漏。随后,Cu2+离子破坏了细菌的呼吸链,产生了大量活性氧物质,抑制细菌的生长。同时,Cu2+离子破坏细菌基因的复制和扩增而产生了基因毒性。考虑到Ti-6Al-4V-5Cu合金中Cu离子溶出的潜在毒性,论文选用MC3T3-El细胞采用SEM观察、MTT、细胞骨架、细胞凋亡等实验对Ti-6Al-4V-5Cu的细胞毒性进行了研究,结果表明：合金表面的细胞贴壁生长,形态正常并具有完整的细胞骨架轮廓,几乎观察不到死细胞,无早期凋亡迹象,显示出极佳的生长状态,细胞增殖率远高于75%, Ti-6Al-4V-5Cu合金显示出良好的细胞相容性。Ti-6Al-4V-5Cu的溶血率为0.6%,显示出良好的血液相容性。初步研究结果也证明了Ti-6Al-4V-5Cu具有一定的促成骨作用,其中Cu离子起到关键性作用。基于以上实验,给出了Ti-6Al-4V-5Cu具有杀菌效果却无细胞毒性的合理性解释：1)细菌和细胞本身的大小尺寸及结构对外界不良刺激的适应性调整差异性；2)细菌与细胞与材料作用时间的差异性,细菌一般在24 h内被杀死；3)前后期Cu离子溶出量差异性,材料前期Cu离子溶出速率较大。耐腐蚀性能与生物安全性有着密切关系,采用电化学方法对Ti-6Al-4V-5Cu的腐蚀性能进行了研究。Ti-6Al-4V-5Cu在生理盐水和Hank's溶液中均具有良好的耐腐蚀性能,点蚀电位分别为1.37 V和1.5 V,符合人体植入物材料的耐腐蚀标准。综上,Ti-6Al-4V-5Cu具有良好的耐腐蚀性、细胞相容性和血液相容性。在不明显改变现有钛合金的优良性能的基础上,同时具有强烈的抗菌功能,将会成为极具临床应用潜力的新型生物医用金属材料。
[Abstract]:Titanium alloy is an ideal biomedical material with good biocompatibility, comprehensive mechanical properties, machinability and corrosion resistance. It is widely used in oral and orthopaedic implants. Therefore, how to control the post-implant infection is a thorny problem that plagues medical staff and attracts more and more attention. In view of these problems, how to ensure the mechanical properties and corrosion resistance of Ti-6Al-4V, which is widely used in orthopedics and dentistry, is highly effective. Based on this design idea, a new type of Ti-6Al-4V alloy was designed and developed by adding an appropriate amount of Cu element with antibacterial function, optimizing the original alloy with appropriate casting, forging and heat treatment processes. Ti-6Al-4V-XCu as-cast titanium alloys with different Cu contents were studied by analyzing the microstructure, mechanical properties, antibacterial properties and corrosion resistance of the alloys. The optimum addition of Cu to Ti-6Al-4V-XCu was determined to be 5%. The hot deformation properties of Ti-6Al-4V-5Cu were studied by GLEEBLE3800 thermal simulator. The results showed that the rheological behavior of the alloys was good. The force increases with the increase of strain rate and the decrease of temperature. After a small deformation variable, the flow stress of the alloy reaches its peak value, and then the continuous softening occurs. The instability zone of the hot working diagram of Ti-6Al-4V-5Cu is small. When the deformation temperature is 900-1050.C and the strain rate is 0.001-0.1 s-1, the power dissipation factor reaches 0.48. The constitutive equation for hot deformation of Ti-6Al-4V-5Cu is obtained: _=6.700*1012[sinh(0.014)]2.809exp(-320*103/RT)_=71.4291n{(Z/6.700*1012)1/2809+[(Z/6.700*1012)2/2.809+1]1/2}-6Al-4V-5Cu material after forging and heat treatment. The results show that the optimum heat treatment regime for the comprehensive properties of Ti-6Al-4V-5C u is heating 930.C water quenching + aging air cooling at 600 _ C. The effect of microstructure on the dissolution of Cu2+ and the antibacterial properties of the alloy is discussed by studying the distribution and dissolution mechanism of C u in Ti-6Al-4V-5C U. In Ti-6Al-4V-5Cu, u mainly exists in phase A and phase P in the form of solid solution and intermetallic compound Ti2Cu. Because of the stronger chemical stability of intermetallic compounds, Cu2+ ions are easier to dissolve in the form of solid solution. In addition, the solubility of Cu in the phase P is higher than that in the phase alpha. Heat treatment can change the ratio of alpha to beta, thus changing the ratio of Cu. Distribution of Cu in the alloy. When the P phase in the alloy increases, the distribution of Cu in the alloy is uniform and dispersed, and the dissolution of Cu 2+ ion is easier. The antibacterial property of the alloy is enhanced. The antibacterial property of Ti-6Al-4V-5Cu is investigated by coating method, surface morphology observation and fluorescence staining, and the gradient concentration of Cu 2+ ion is determined for Staphylococcus aureus. The results showed that Ti-6Al-4V-5Cu had strong killing effect on E.coli and Staphylococcus aureus, and could effectively inhibit the formation of bacterial biofilm. The minimum inhibitory concentration of Cu2+ to Staphylococcus aureus was 100 ug/g. The antimicrobial mechanism of L.Ti-6Al-4V-5Cu is that when the alloy contacts with the bacterial liquid, a small amount of Cu2+ ions dissolve from the alloy, and the concentration gradient drives the Cu2+ ions to diffuse from the alloy surface to the bacterial liquid. When the alloy contacts with the bacteria, the bacterial membrane is destroyed and the permeability of the bacterial membrane is increased, resulting in the leakage of proteins and reducing sugars in the bacteria. 2+ ions destroyed the respiratory chain of bacteria, produced a large number of reactive oxygen species, inhibited the growth of bacteria. At the same time, Cu2+ ions destroyed the replication and amplification of bacterial genes, resulting in genotoxicity. Considering the potential toxicity of the dissolution of Cu ions from Ti-6Al-4V-5Cu alloy, MC3T3-El cells were observed by SEM, MTT, cytoskeleton and apoptosis. The cytotoxicity of Ti-6Al-4V-5Cu was studied by experiments. The results showed that Ti-6Al-4V-5Cu alloy surface cells adhered to the wall and grew normally with complete cytoskeleton contour, almost no dead cells were observed, and no early apoptosis was observed. The cell proliferation rate was much higher than 75%. Ti-6Al-4V-5Cu alloy showed good performance. The hemolysis rate of Ti-6Al-4V-5Cu was 0.6%, showing good blood compatibility. The preliminary results also proved that Ti-6Al-4V-5Cu could promote bone formation, in which Cu ion played a key role. Bacteria and cell size and structure of their own adaptation to external adverse stimuli to adjust differences; 2) bacteria and cell-to-material interaction time differences, bacteria are generally killed within 24 hours; 3) before and after the dissolution of Cu 2+ difference, material early dissolution rate of larger Cu 2+ corrosion resistance and biological safety has a close relationship. The corrosion resistance of Ti-6Al-4V-5Cu was studied by electrochemical method. The corrosion resistance of Ti-6Al-4V-5Cu was good in normal saline and Hank's solution. The pitting potential of Ti-6Al-4V-5Cu was 1.37 V and 1.5 V respectively, which accorded with the corrosion resistance standard of human implant materials. Compatibility and blood compatibility. On the basis of not obviously changing the excellent properties of existing titanium alloys, and having strong antibacterial function, it will become a new type of Biomedical Metal materials with great clinical application potential.
【学位授予单位】：大连理工大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：TG146.23

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