K_2Ti_6O_（13）/Ti基生物医学材料的制备及生物相容性研究
摘要
针对Ti基生物医学材料在临床应用中遇到的关键问题—成本和性能，本研究设计开发了一套新型的材料制备工艺以降低成本，研制了新型的K_2Ti_6O_(13)涂层／Ti基生物医学材料以提高材料的生物学性能，并对涂层的表面形貌、相组成、结合强度以及涂层的生物相容性和生物活性进行了观察、分析与评估。研究结果表明：
氮、氧污染的临界氧分压和氮分压是一个温度的函数，并随温度的升高而急剧增大。采用多次抽真空反充惰性气体Ar的方法可有效降低氧、氮分压。本实验采用10~4Pa充Ar压强+3次抽充循环，可有效避免氮、氧对Ti合金的污染：防污染CaO基坩埚涂层的设计和制作，可有效避免石墨坩埚的C污染，为低成本Ti合金的生物学应用创造了条件。
K_2CO_3与TiO_2的摩尔比及煅烧温度是决定钛酸钾产物的主要因素。煅烧温度和时间通过对自生氧化层的作用影响涂层质量和结合强度。原位KDC煅烧工艺的确立必须综合考虑K_2CO_3液相基质、钛的同素异构转变和自生氧化层的影响，同时兼顾煅烧温度和煅烧时间的最佳匹配。K_2Ti_6O_(13)涂层的合成过程可以用一个“包围—反包围”的反应过程来描述。本研究以1050℃煅烧0.5～1h的涂层质量为最佳。KDC煅烧产物主要是白色针状的K_2Ti_6O_(13)晶须，直径和长度分别在1μm和10μm左右。涂层厚度约为6μm，表面粗糙度为1.2μm～1.8μm，适宜表面粗糙度为骨的向内生长提供有利的位置。涂层与基体结合牢固，结合强度可达24MPa以上，是纯HA涂层结合强度的2倍，并能够经受空冷条件下的冷热冲击。膨胀系数的良好匹配、自生氧化层对合成反应的参与以及抛锚效应是高结合强度的主要原因。摩擦磨损实验表明涂层具有良好的耐磨性。
经模拟体液浸泡，涂层表面形成了钙磷比接近人体骨骼的钙磷层。钙磷生长层是为多孔的网状结构，这种结构有利于人体新陈代谢过程中营养物质的传输和骨的生长以及废物的排泄，蜂窝框架又确保了新生骨质具有一定的强度，这表明K_2Ti_6O_(13)涂层具有良好的生物活性。
血液相容性试验表明：与Co-Cr合金相比，K_2Ti_6O_(13)／Ti基生物医学材料的凝血时间较长；K_2Ti_6O_(13)／Ti的血小板粘附量明显少于Co-Cr合金和不锈钢，表明其血液相容性显著优于Co-Cr合金和不锈钢。
经过7天的细胞培养，K_2Ti_6O_(13)／Ti基生物医学材料中的骨细胞繁殖到了6倍左右，与不锈钢和基体钛合金相比，K_2Ti_6O_(13)／Ti具有更优越的生物相容性和生物活性。
To solve the cost and property problems met in the clinical application of titanium matrix biomedical materials, a new set of fabrication technology has been designed and developed to reduce the production cost in this study, and a new type of K2Ti6O13 /Ti matrix biomedical material has been manufactured to improve the biomedical properties. Surface morphology, phase constitution, bonding strength, biocompatibility and bioactivity of the coating were analyzed and evaluated. The results indicate as follows:
The critical partial pressures of oxygen and nitrogen are both functions of temperature. Oxygen and nitrogen partial pressures can be sufficiently lowered by pumping and argon inflating for many times. Oxygen and nitrogen contamination to titanium alloy is effectively avoided by three times of pump-inflation circulation with the argon inflation pressure of 104Pa. The designation and fabrication of CaO matrix coating of the crucible makes it possible to avoid the carbon contamination from graphite crucible. All above will create conditions for the biology application of the low cost titanium alloys.
The K/T ratio and the culcination temperature are the principal factors to determine which kind of potassium titanate to form. Culcination temperature and time influence the self-generated oxide layer, and then act on the coating's quality and bonding strength. To establish the in situ KDC process, the influences of the K2CO3 liquid phase stroma, the same element-different structure transfermation of titanium, the self-generated oxide layer should be taken into consideration, and the culcination temperature and time should also match best. We can depict the synthesis process of K2Ti6O13 as a model of 'surround'-'counter-surround'. In this study, the coating gets the best quality at temperature of 1050Cculcinating for 0.5~1hour. The culcination product is mainly white spiny K2Ti6O13 crystal whisker whose diameter and length are 1 μm and 10μm respectively. The coating thickness is 6μm, and the surface roughness is 1.2μm~ 1.8μm. The suitable surface roughness provide advantages for ingrowth of bone. The bonding strength between coating and matrix is as high as 24MPa, which doubles the one of HA coating. Furthermore, the K2Ti6O13 coating can bear the cold-hot impact during air-cool process. The main reasons of the high bonding strength are as follows: the suitable match of expand coefficient, the participation to the synthetic reaction of the self-generated oxide layer, and anchor dropping effect. Friction wear experiment shows that the coating has good wear-resistance.
After immersion in the simulate body fluid (SBF), a calcium-phosphorus layer, whose calcium-phosphorus scale is near to the human bone's, is formed on the coating. The calcium-phosphorus layer has porous reticulation structure, which is beneficial to the nourishment transmission, bone ingrowth and scrap excretion during the body metabolism. The honeycomb-like frame insures the bone certain strength. These above makes clear that K2Ti6On coating has good bioactivity.
Haemocompatibility experiment finds that the blood clotting time of K2Ti6On/Ti matrix biomedical materials is much longer than that of Co-Cr alloy; and the platelet sticking number on K2Ti6O13/Ti alloy is obviously less than those on the Co-Cr alloy and 316L stainless steel. These indicate that the Haemocompatibility of K2Ti6O]3/Ti alloy is remarkably superior to the Co-Cr alloy and the 316L stainless steel.
Cell cultivation experiment indicates that the cytodensity in the hole with K2Ti6O13/Ti matrix biomedical materials is as high as six times of the initial inoculation density after seven days of cultivation. The K2Ti6O13/Ti alloy has superior biocompatibility and bioactivity as compared with 316L stainless steel and Ti alloy without coating.
氮、氧污染的临界氧分压和氮分压是一个温度的函数，并随温度的升高而急剧增大。采用多次抽真空反充惰性气体Ar的方法可有效降低氧、氮分压。本实验采用10~4Pa充Ar压强+3次抽充循环，可有效避免氮、氧对Ti合金的污染：防污染CaO基坩埚涂层的设计和制作，可有效避免石墨坩埚的C污染，为低成本Ti合金的生物学应用创造了条件。
K_2CO_3与TiO_2的摩尔比及煅烧温度是决定钛酸钾产物的主要因素。煅烧温度和时间通过对自生氧化层的作用影响涂层质量和结合强度。原位KDC煅烧工艺的确立必须综合考虑K_2CO_3液相基质、钛的同素异构转变和自生氧化层的影响，同时兼顾煅烧温度和煅烧时间的最佳匹配。K_2Ti_6O_(13)涂层的合成过程可以用一个“包围—反包围”的反应过程来描述。本研究以1050℃煅烧0.5～1h的涂层质量为最佳。KDC煅烧产物主要是白色针状的K_2Ti_6O_(13)晶须，直径和长度分别在1μm和10μm左右。涂层厚度约为6μm，表面粗糙度为1.2μm～1.8μm，适宜表面粗糙度为骨的向内生长提供有利的位置。涂层与基体结合牢固，结合强度可达24MPa以上，是纯HA涂层结合强度的2倍，并能够经受空冷条件下的冷热冲击。膨胀系数的良好匹配、自生氧化层对合成反应的参与以及抛锚效应是高结合强度的主要原因。摩擦磨损实验表明涂层具有良好的耐磨性。
经模拟体液浸泡，涂层表面形成了钙磷比接近人体骨骼的钙磷层。钙磷生长层是为多孔的网状结构，这种结构有利于人体新陈代谢过程中营养物质的传输和骨的生长以及废物的排泄，蜂窝框架又确保了新生骨质具有一定的强度，这表明K_2Ti_6O_(13)涂层具有良好的生物活性。
血液相容性试验表明：与Co-Cr合金相比，K_2Ti_6O_(13)／Ti基生物医学材料的凝血时间较长；K_2Ti_6O_(13)／Ti的血小板粘附量明显少于Co-Cr合金和不锈钢，表明其血液相容性显著优于Co-Cr合金和不锈钢。
经过7天的细胞培养，K_2Ti_6O_(13)／Ti基生物医学材料中的骨细胞繁殖到了6倍左右，与不锈钢和基体钛合金相比，K_2Ti_6O_(13)／Ti具有更优越的生物相容性和生物活性。
To solve the cost and property problems met in the clinical application of titanium matrix biomedical materials, a new set of fabrication technology has been designed and developed to reduce the production cost in this study, and a new type of K2Ti6O13 /Ti matrix biomedical material has been manufactured to improve the biomedical properties. Surface morphology, phase constitution, bonding strength, biocompatibility and bioactivity of the coating were analyzed and evaluated. The results indicate as follows:
The critical partial pressures of oxygen and nitrogen are both functions of temperature. Oxygen and nitrogen partial pressures can be sufficiently lowered by pumping and argon inflating for many times. Oxygen and nitrogen contamination to titanium alloy is effectively avoided by three times of pump-inflation circulation with the argon inflation pressure of 104Pa. The designation and fabrication of CaO matrix coating of the crucible makes it possible to avoid the carbon contamination from graphite crucible. All above will create conditions for the biology application of the low cost titanium alloys.
The K/T ratio and the culcination temperature are the principal factors to determine which kind of potassium titanate to form. Culcination temperature and time influence the self-generated oxide layer, and then act on the coating's quality and bonding strength. To establish the in situ KDC process, the influences of the K2CO3 liquid phase stroma, the same element-different structure transfermation of titanium, the self-generated oxide layer should be taken into consideration, and the culcination temperature and time should also match best. We can depict the synthesis process of K2Ti6O13 as a model of 'surround'-'counter-surround'. In this study, the coating gets the best quality at temperature of 1050Cculcinating for 0.5~1hour. The culcination product is mainly white spiny K2Ti6O13 crystal whisker whose diameter and length are 1 μm and 10μm respectively. The coating thickness is 6μm, and the surface roughness is 1.2μm~ 1.8μm. The suitable surface roughness provide advantages for ingrowth of bone. The bonding strength between coating and matrix is as high as 24MPa, which doubles the one of HA coating. Furthermore, the K2Ti6O13 coating can bear the cold-hot impact during air-cool process. The main reasons of the high bonding strength are as follows: the suitable match of expand coefficient, the participation to the synthetic reaction of the self-generated oxide layer, and anchor dropping effect. Friction wear experiment shows that the coating has good wear-resistance.
After immersion in the simulate body fluid (SBF), a calcium-phosphorus layer, whose calcium-phosphorus scale is near to the human bone's, is formed on the coating. The calcium-phosphorus layer has porous reticulation structure, which is beneficial to the nourishment transmission, bone ingrowth and scrap excretion during the body metabolism. The honeycomb-like frame insures the bone certain strength. These above makes clear that K2Ti6On coating has good bioactivity.
Haemocompatibility experiment finds that the blood clotting time of K2Ti6On/Ti matrix biomedical materials is much longer than that of Co-Cr alloy; and the platelet sticking number on K2Ti6O13/Ti alloy is obviously less than those on the Co-Cr alloy and 316L stainless steel. These indicate that the Haemocompatibility of K2Ti6O]3/Ti alloy is remarkably superior to the Co-Cr alloy and the 316L stainless steel.
Cell cultivation experiment indicates that the cytodensity in the hole with K2Ti6O13/Ti matrix biomedical materials is as high as six times of the initial inoculation density after seven days of cultivation. The K2Ti6O13/Ti alloy has superior biocompatibility and bioactivity as compared with 316L stainless steel and Ti alloy without coating.
引文
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73．周彦邦．钛合金铸造概论．北京：航空工业出版社，2000．2
74．常辉．日本开发的几种钛合金及其应用．钛工业进展，1998，6：31-33
75．魏寿庸，祝瀑，何瑜，等．Ti-6.5Al-2.5Sn-4Zr-1Nb-0.7Mo-0.15Si钛合金．钛工业进展，1999，6：26-31
76．郑明新．工程材料(第二版)．北京：清华大学出版社，1991．208
77．叶应妩，李健斋，王玉琛，等．临床实验诊断学．北京：人民卫生出版社，1980．1129
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84．[日]植村益次等编，贾丽霞等译．高性能复合材料最新技术．北京：中国建筑出版社，1989．1
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86．朱文化，柯家俊．新型无机晶须——钛酸钾晶须．化学通报，1994，4：5～10
87．谢凯，盘毅，王秀华，等．钛酸钾短纤维的制备工艺研究．无机盐工业，1997，1：16～25
88．卫中山，强立锋，吴申庆．钛酸钾晶须增强铝基复合材料的研究现状．特种铸造及有色合金，2000，1：54～55
89. T. Imai, Y. Nishida, M. Yamada, et al.. K_2O·6TiO_2 whisker-reinforced aluminium composite by a powder metallurgical method. J. Mater. Sci. Letters, 1987, 6:1257-1258
90．千千和，史郎．酸纤维．塑料，1980，31(8)：106
91. Kyo-Han Kim, X. L. Zhu and Won-Woo Son. Formation and Morphology of Anodic Oxide Film of Ti. J. Mater. Sci. Technol., 2001, 17(1):33