自生纳米级二氧化钛颗粒/钛合金生物材料制备及生物学特性
|
摘要
生物相容性是钛基生物医用材料研究中应首先考虑的重要问题之一。为了提高材料的生物相容性，本研究对自制的钛基体进行了二氧化钛涂层的制备和表面碱液生物活化处理的研究，并采用模拟体液培养实验和细胞培养实验评价了表面改性后材料的生物相容性和生物活性，对基体以及表面改性后材料的组织形貌、相组成和生物相容性进行了观察、分析与评估。
采用非自耗真空电弧凝壳炉熔炼钛及钛合金，并对钛合金的组织及性能进行观察和测定，分析了电弧炉熔炼钛合金的结晶特点。实验中选用的合金元素有Mo、Nb、Zr、Fe等，均为β稳定元素。
钛及其合金具有良好的抗蚀性和生物相容性与其表面的氧化膜ZiO_2有关，基于此，采用不同工作介质条件制备了二氧化钛涂层。本研究采用包埋烧结法分别在常压和真空条件下在钛合金试样上制备二氧化钛功能涂层，并对涂层的表面形貌和相组成进行了分析。发现制备的二氧化钛功能涂层中晶粒尺寸为微米级，晶型主要为金红石型二氧化钛，表面粗糙度值大小不一。
涂层的表面粗糙度对于材料的生物活性有直接影响。为了改变涂层表面的粗糙度，实验中从改变涂层粉末的粒度入手，以钛酸丁酯为原料，通过醇盐水解法制备了纳米级锐钛矿型TiO_2超细粉，粒径约为5～10nm，而普通二氧化钛粉体的粒径多在100nm左右。用纳米二氧化钛粉包埋钛合金试样烧结制备的涂层表面粗糙度值Ra在2.1～2.3μ m之间，相对于普通二氧化钛粉包埋烧结的涂层来说，粗糙度较低。纳米二氧化钛涂层的晶粒直径在50nm～70nm之间，偶有小于50nm的小晶粒。
除了在钛合金表面制备涂层外，还尝试了对钛合金基体表面直接采用碱液处理的方法进行表面生物活化。具体为运用统计学原理，在不同温度下(60℃～100℃)用不同浓度(5M～10M)的氢氧化钠溶液处理不同的钛合金基体，以确定最佳的生物活化处理条件。
利用模拟体液培养实验对表面改性后材料的生物相容性和生物活性进行了评估。在培养相同的时间后，发现纳米TiO_2／Ti合金沉积磷灰石的能力最强。不同表面改性方法的SBF培养结果比较为：纳米二氧化钛涂层＞碱液处理方法＞常压下烧结二氧化钛涂层＞真空下烧结制备的涂层。
对纳米二氧化钛／钛合金生物材料进行细胞培养实验，发现该材料具有良好的细胞相容性。
Biocompatibility is one of the most considerable problems in the study of Ti matrix biomedical material. In order to improve titanium alloy's biocompatibility, the titanium dioxide coating was fabricated on Ti matrix. Besides, the surface of titanium alloys was directly disposed by alkali to make it possess bioactivity. Biocompatibility and bioactivity of the material after surface modification were evaluated through the simulated body fluid (SBF) cultivation and cell cultivation experiment. Surface morphology, phase constitution and biocompatibility of the material were analyzed and evaluated in this paper.
Titanium alloys were prepared by non-consumable vacuum arc smelting furnace. And the microstructures and the properties of titanium alloys were investigated. The structure character of cast titanium alloys was studied. The alloy elements selected in this experiment were Mo, Nb, Zr and Fe, which were β stable elements.
The excellent resist erosion and biocompatibility of pure titanium and titanium alloys are attributed to the TiO2 film on the surface. So the titanium dioxide coatings were fabricated by cladding substrates to sinter in different work mediums, which included normal pressure and vacuum conditions. The surface morphology and phase constitution of coatings were analyzed. The results indicated that the crystal particles in coatings were mostly rutile, and the size of the rutile was in a micrometer grade. The surface roughness of coatings was different.
Surface roughness of coatings affects the bioacitivity of materials, In order to change the roughness of coatings, the granularity of coating powders was changed firstly. Nanometeral anatase titanium dioxide powders were prepared by hydrolysis of titanium-tetrabutoxide with ethanol in this paper. The main particle size is between 5nm and 10nm, while the size of ordinary titanium dioxide powders is about 100nm. The nanoparticles coating was fabricated by cladding titanium alloys with nano-TiO2 powders, and its surface roughness was 2.1-2.3 μ m which was smaller than that of ordinary titanium dioxide coatings. The diameter of crystal particle in nano-coatings is mainly between 50nm and 100nm, and sometimes less than 50nm.
In addition to fabricate coatings on the surface of titanium alloys, the bioactivities on the
surface of titanium alloy substrates were done by alkali solution. Making use of statistical principle, the different Ti substrates were dealt with in different temperatures(60℃~100℃) by different concentrations(5M~10 M) NaOH solutions so that we can confirm the most appropriate technique.
Biocompatibility and bioactivity of the material after surface modification were evaluated through the simulated body fluid cultivation experiment. After cultivated for same days, the capability of Ca phosphates deposition of nano-TiO2/Ti alloys was the best. The SBF cultivation results by different surface modification methods were: nano-TiO2 coating > alkali solution treatment > TiO2 coatings sintered in normal pressure > TiO2 coatings sintered in vacuum.
The nano-TiO2/Ti alloys possessed favorable cell compatibility testified by the cell cultivation experiment.
采用非自耗真空电弧凝壳炉熔炼钛及钛合金，并对钛合金的组织及性能进行观察和测定，分析了电弧炉熔炼钛合金的结晶特点。实验中选用的合金元素有Mo、Nb、Zr、Fe等，均为β稳定元素。
钛及其合金具有良好的抗蚀性和生物相容性与其表面的氧化膜ZiO_2有关，基于此，采用不同工作介质条件制备了二氧化钛涂层。本研究采用包埋烧结法分别在常压和真空条件下在钛合金试样上制备二氧化钛功能涂层，并对涂层的表面形貌和相组成进行了分析。发现制备的二氧化钛功能涂层中晶粒尺寸为微米级，晶型主要为金红石型二氧化钛，表面粗糙度值大小不一。
涂层的表面粗糙度对于材料的生物活性有直接影响。为了改变涂层表面的粗糙度，实验中从改变涂层粉末的粒度入手，以钛酸丁酯为原料，通过醇盐水解法制备了纳米级锐钛矿型TiO_2超细粉，粒径约为5～10nm，而普通二氧化钛粉体的粒径多在100nm左右。用纳米二氧化钛粉包埋钛合金试样烧结制备的涂层表面粗糙度值Ra在2.1～2.3μ m之间，相对于普通二氧化钛粉包埋烧结的涂层来说，粗糙度较低。纳米二氧化钛涂层的晶粒直径在50nm～70nm之间，偶有小于50nm的小晶粒。
除了在钛合金表面制备涂层外，还尝试了对钛合金基体表面直接采用碱液处理的方法进行表面生物活化。具体为运用统计学原理，在不同温度下(60℃～100℃)用不同浓度(5M～10M)的氢氧化钠溶液处理不同的钛合金基体，以确定最佳的生物活化处理条件。
利用模拟体液培养实验对表面改性后材料的生物相容性和生物活性进行了评估。在培养相同的时间后，发现纳米TiO_2／Ti合金沉积磷灰石的能力最强。不同表面改性方法的SBF培养结果比较为：纳米二氧化钛涂层＞碱液处理方法＞常压下烧结二氧化钛涂层＞真空下烧结制备的涂层。
对纳米二氧化钛／钛合金生物材料进行细胞培养实验，发现该材料具有良好的细胞相容性。
Biocompatibility is one of the most considerable problems in the study of Ti matrix biomedical material. In order to improve titanium alloy's biocompatibility, the titanium dioxide coating was fabricated on Ti matrix. Besides, the surface of titanium alloys was directly disposed by alkali to make it possess bioactivity. Biocompatibility and bioactivity of the material after surface modification were evaluated through the simulated body fluid (SBF) cultivation and cell cultivation experiment. Surface morphology, phase constitution and biocompatibility of the material were analyzed and evaluated in this paper.
Titanium alloys were prepared by non-consumable vacuum arc smelting furnace. And the microstructures and the properties of titanium alloys were investigated. The structure character of cast titanium alloys was studied. The alloy elements selected in this experiment were Mo, Nb, Zr and Fe, which were β stable elements.
The excellent resist erosion and biocompatibility of pure titanium and titanium alloys are attributed to the TiO2 film on the surface. So the titanium dioxide coatings were fabricated by cladding substrates to sinter in different work mediums, which included normal pressure and vacuum conditions. The surface morphology and phase constitution of coatings were analyzed. The results indicated that the crystal particles in coatings were mostly rutile, and the size of the rutile was in a micrometer grade. The surface roughness of coatings was different.
Surface roughness of coatings affects the bioacitivity of materials, In order to change the roughness of coatings, the granularity of coating powders was changed firstly. Nanometeral anatase titanium dioxide powders were prepared by hydrolysis of titanium-tetrabutoxide with ethanol in this paper. The main particle size is between 5nm and 10nm, while the size of ordinary titanium dioxide powders is about 100nm. The nanoparticles coating was fabricated by cladding titanium alloys with nano-TiO2 powders, and its surface roughness was 2.1-2.3 μ m which was smaller than that of ordinary titanium dioxide coatings. The diameter of crystal particle in nano-coatings is mainly between 50nm and 100nm, and sometimes less than 50nm.
In addition to fabricate coatings on the surface of titanium alloys, the bioactivities on the
surface of titanium alloy substrates were done by alkali solution. Making use of statistical principle, the different Ti substrates were dealt with in different temperatures(60℃~100℃) by different concentrations(5M~10 M) NaOH solutions so that we can confirm the most appropriate technique.
Biocompatibility and bioactivity of the material after surface modification were evaluated through the simulated body fluid cultivation experiment. After cultivated for same days, the capability of Ca phosphates deposition of nano-TiO2/Ti alloys was the best. The SBF cultivation results by different surface modification methods were: nano-TiO2 coating > alkali solution treatment > TiO2 coatings sintered in normal pressure > TiO2 coatings sintered in vacuum.
The nano-TiO2/Ti alloys possessed favorable cell compatibility testified by the cell cultivation experiment.
引文
[1]顾汉卿，徐国风．生物医学材料学．天津：天津科技翻译出版公司，1993．8
[2]顾汉卿．生物医学材料的现状及发展(一)．中国医疗器械信息，2001，7(1)：45-48
[3]高景恒．加速我国医用生物材料的研究与开发．实用美容整形外科杂志，1998，9(3)：113-114
[4]杨国营．生物医用材料．河北化工，2002，4：17-19
[5]田文华．生物材料和医用植入物科学——现在和未来展望．国外医学生物医学工程分册，1997，20(4)：253-256
[6]李世普．生物医用材料导论．湖北：武汉工业大学出版社，2000．8
[7]俞耀庭，张兴栋．生物医用材料．天津：天津大学出版社．2000．12
[8]Yanashitak U. Immobilization of yeast cell in porous silica carrier with Sol-Gel process. J Ceram Society Japan, 1992, 100.. 426-429
[9]Song C X, Labhasetwar V, Murphy H, et al. Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery. J Controlled Rellease, 1997, 43: 197-212
[10]Poggie RA, Kovacs P, Davidson JA. Oxygen diffusion hardening of Ti-Nb-Zr alloys. Mater Manuf Processes, 1996, 11 (2): 185-197
[11]崔福斋，冯庆玲．生物材料学．北京：科学出版社．1997．6
[12]杨晓芳，奚廷斐．生物材料生物相容性评价研究进展．生物医学工程学杂志，2001，18(1)：123-128
[13]TC150LS05832. Implants for Surgery-Metallic Materials, Part1-12, 1999
[14]Ninomi M, Kuroda D,Fukunaga K, et al. Corrosion wear fracture of new β type biomedical titanium alloys[J]. Mater Sci Eng, 1999, A263:193-199
[15]阮建明，Grant M H，黄伯云．金属毒性研究(Ⅰ)[J]．中国有色金属学报，2001，11(6)：960-965
[16]阮建明，Grant M H，黄伯云．金属毒性研究(Ⅱ)[J]．中国有色金属学报，2002，12(1)：14-19
[17]Kathy Wang. The use of titaniumfor medicalapplicationsinthe USA. Mater. Sci. and Eng., 1996, A213: 134-137
[18]佐佐木 佳男，松下富春．人工骨关节用新二合金金属，1996，66(19)：64-69
[19]宁聪琴，周玉．医用钛合金的发展及研究现状．材料科学与工艺，2002，10(1)：100-106
[20]Tengvall P, Lundstrom I. Physico-chemical considerations of titanium as a biomaterial [J]. Clin Mater, 1992, 9:115-134
[21][英]威廉姆斯 D F主编，朱鹤孙等译．医用与口腔材料．见：卡恩R W，哈森P，克雷默E J主编．材料科学与技术丛书．北京：科学出版社，1999．29-63
[22]Parks G A. The isoelectric point of solid oxides, solid hydroxides, and aqueous hydroxy complex system [J]. ChemRev, 1965, 65:177-198
[23]HenchLL. Bioceramic: from concept to clinic [J]. JAmCeram Soc, 1991, 74:1487-1510
[24]Kokubo T. Bioactive glass-ceramics: properties and applications [J]. Biomaterials, 1991, 12: 155-163
[25]Li P, Kangasniemi I, De Groot K, et al. Bone like hydroxyapatite induction by a gel-derived titania on atitanium substrate [J]. J Am Ceram Soc, 1994, 77:1307-1312
[26]FendorfM, Gronsk R. Surface precipitation reaction on oxide surfaces [J]. J Colloid Interface Sci, 1992, 148:295-298
[27]Bruneel N, Helsen J. In-vitro simulation of biocompatibility of titanium [J]. J Biomed Mater Res, 1988, 22:203-214
[28]程奎，翁文剑，葛曼珍．生物陶瓷涂层[J]．材料科学与工程，1998，16(3)：8-12
[29]陈安玉．口腔种植学[M]．成都：四川科学技术出版社，1991．64
[30]Rostlund T, Mckellop H, Albrektsson B, et al. Wear of ion implanted pure titanium against UHMWPE [J]. Biomaterials, 1989, 10:176-181
[31]Perry A. Ion implantation of titanium alloys for biomaterial and other applications[J]. Surf Eng, 1987, 3: 154-159
[32]Mohammadi S, Wictorin L, Ericsonetal L E. Cast titanium as implant material. J Mater. Sci. : Mater Med., 1995, 6:435-444
[33]Ungersboeck A, Geret V, Pohler O, et al. Tissure reaction to bone plates made of pure titanium: a prospective, quantitative clinicalstudy. J. Mater. Sci. : Mater Med., 1995, 6:223-229
[34]Reis R L, Monteiro F J, Hastings G W. Stability of hydroxyapatite plasma-sprayed coated Ti-6A1-4V under cyclic bending in simulated physiological solutions. J Mater. Sci.: Mater Med., 1994, 5:457-462
[35]Gross K A , Berndt C C. In vitro testing of plasma sprayed hydroxyapatite
coatings. J. Mater. Sci.: Mater Med., 1995, 6:214-219
[36]Ong J L, Lucas L C. Post-deposition heat treatments for ion beam sputter deposited calcium phospate coatings [J]. Biomaterials, 1994, 15 (15): 337-341
[37]Ellies L G, Nelson D G A, Featherstone J D B. Crystallographic changes in calcium phosphates during plasma-spraying [J]. Biomaterials, 1992, 13 (5): 313-317
[38]储成林，朱景川，尹钟大，等．医用钛合金及其表面改性．材料科学与工艺，1998，6(2)：40-44
[39]Chang B, Chang W K, Wang B C, et al. Plasma spraying of zirconia-reinforced hydroxyapatite composite coatings on titanium : Part Ⅰ phase microstructure and bonding strength. J. Mater. Sci.: Mater Med., 1997, 8:193-200
[40]Chang B, Chang W K, Wang B C, et al. Plasma spraying of zirconia-reinforced hydroxyapatite composite coatings on titanium: Part Ⅱ dissolution behaviour in simulated body fludi and bonding degradation. J. Mater. Sci.: Mater Med., 1997, 8:201-211
[41]Chernlin J H, Liu M L, Ju C P. Structure and properties of hydroxyapatite-bioactive glass composites plasma sprayed on Ti6Al4V. J. Mater. Sci.: Mater Med., 1994, 5:279-283
[42]曾晟宇，赵乃勤，崔振铎，等．金属生物材料表面改性研究的进展．材料保护，2000，33(1)： 5-8
[43]Olbrich Kevin C, Andersen Thomas T, Blumenstock Frank A, et al. Surfaces modified with covalently-immobilized adhesive peptides affect fibroblast population motility[J]. Biomaterials, 1996, 17 (8): 759-764
[44]Narayan J, Fan W D, Narayan R J, et al. Diomond, diamone-like and titanium nitride biocompatible coatings for human body parts. Mater. Sci. and Eng., 1994, B25:5-10
[45]Grant D M, Lo W J, Parker K G, et al. Biocompatible and mechanical properties of low temperature deposited quaternary (Ti, AI, V, N) coatings on Ti6AI4V titanium alloy substrates
[46]金自宜．钛系生物医学工程材料．材料导报，1993，2：18-23
[47]冯颖芳，康浩方，张震．钛合金医用植入物材料的研究及应用．稀有金属，2001，25(5)：349-354
[48]劳金海．钛在生物医学中应用的新发展．上海钢研，2001，4：60-62
[49]冈崎义光．各种金属细胞适合性生体用新合金开发，1998，37(10)：838-842
[50]槁隆夫．金属系生体材料表面改质． 1998，37(10)：853-855
[51]金铉敏，宫路史明，小久保正．化学处理倾斜机能生体活性合金调制．日本金属学会志，1998，62(11)：1102-1107
[52]野浪亨，长沼胜义，龟山哲也．超塑性利用生体用合金的接合．1998，37(10)：856-858
[53]Thomas K A, Kay J F, Cook S D, et al. The effect of surface macrotexture and hydroxylapatite coating on the mechanical strengths and histologic profiles of titanium implant materials. J Biomed Mater Res, 1987, 21:1395
[54]周彦邦．钛合金铸造概论．北京：航空工业出版社，2000．2
[55]Kokubo T. Bioactivity of glass and glasses-ceramics. In: Ducheyne P, Kokubo T, Blitterswijk CA, editors. Handbook of bioactive ceramics, Vol. 1: bone-bonding biomaterials, Reed healthcare communications. The Netherlands: Leiden, 1992, 31-46
[56]Kokubo T, Ito S, Huang Z T, et al. Ca, P-rich layer formed on high-strength bioactive glass-ceramic A-W . J Biomed Mater Res, 1990, 24:331-343
[57]Kokubo T, Kushitani H, Sakka S, et al. Solution able to reproduce in vivo surface-structure changes in bioactive glass-ceramics A-W. J Biomed Mater Res, 1990, 24: 721-734
[58]《有色金属提取冶金手册》编辑委员会．有色金属提取冶金手册，稀有高熔点金属(上)，北京：冶金工业出版社，1999
[59]Song Y, Xu D S, Yang R, et al. Theoretical study of the effects of alloying elements on the strength and modulus of β -type bio-titanium alloys. Mater. Sci. Eng, 1999, A260: 269-274
[60]1986. 45
[61]侯增寿，卢光熙．金属学原理．上海：上海科学技术出版社。1998．3
[62][苏]E．A．鲍利索娃等著，陈石卿译．钛合金金相学．北京：国防工业出版社．1986．4
[63]李晓娥，祖庸．液相法合成纳米二氧化钛[J]．钛工业进展，1997，3：14-17
[64]Amarchand S, Rama Mohan T R, Ramakrishnan P. A novel chemical solution technique for the preparation of nano size titanium powders from titanium dioxide [J]. Advanced Powder Technology, 2000, 11 (4): 415-422
[65]高晓云，张敬畅，王伟洁，等．激光热解法制备TiO_2超微粉[J]．无机材料学报，1993，8(1)： 57-62
[66]李学富．超微细二氧化钛——中高功能化新型无机材料[J]．化工新型材料，1995，23(5)：36-38
[67]李燕．醇—水溶液加热法制备纳米级二氧化钛超细粉[J]．陶瓷学报，2000，21(1)：51-53
[68]张敬畅，曹微良，于定新，等．超临界流体干燥法制备纳米级TiO_2的研究[J]．无机材料学报，1999，14(1)：29-35
[69]周芝骏等编．钛的性质及其应用．北京：高等教育出版社，1993．27-35
[70]张仲燕，邢建南，施利毅，等．纳米二氧化钛颗粒的制备[J]．上海大学学报(自然科学版)，2002，8(1)：87-90
[71]刘河洲．纳米TiO_2的反胶束水解合成与热处理过程动力学研究．上海交通大学博士论文，2000：38-42
[72]陈吉华，杨大智，刘敬肖，等．Ti-Ta-O复合薄膜的制备及抗腐蚀性．材料研究学报，2001，15(5)：587-592
[73]王浩，赵文宽，方佑龄，等．二氧化钛光催化杀灭肿瘤细胞的研究．催化学报，1999，20(3)：373-374
[74]孙康．钛提取冶金物理化学．北京：冶金工业出版社，2001．11
[75]Chen Shihai, Zhang Hongzhi. Oxidation Principle of Metals. Shenyang: Northeastern University Press, 1988:1-16
[76]Zhai Jinkun. High Temperature Corrosion of Metals. Beijing: Beijing Aeronautics & Astronautics University Press, 1994:35-52
[77]冉均学．钛基生物医用材料表面改性及模拟体液培养．河北工业大学硕士论文，2003：32-33
[78]Takadama H, Kim H M, Kokubo T and Nakamura T. XPS study of the process of apatite formation on bioactive Ti-6A1-4V alloy in simulated body fluid. Science and Technology of Advanced Materials, 2001, 2: 389-396
[79]储成林，朱景川，尹钟大，等．HA-Ti/Ti/HA-Ti轴对称生物功能梯度材料的制备及其热应力缓和特性．中国有色金属学报，1999，9(1)：57-62
[80]石玉龙，谢广文．二氧化钛的用途及其薄膜的制备方法．电机电器技术，2000，3：37-41
[81]张峰，李昌荣，王向晖，等．氧化钛薄膜的血液相容性机理探讨．生物医学工程学杂志．2000，17(2)： 146-150
[82]陈俊英，杨萍，冷永祥，等．掺杂氧化钛薄膜的制备与血液相容性研究．功能材料，2000，31(2)： 212-214
[83]黄楠，杨萍，曾小兰，等．Ti-O／Ti-N复合薄膜的离子束合成及人工心脏瓣膜材料表面改性研究，功能材料与器件学报，1997，3(1)：40-46
[84]Kasem O, Band Lausma. J. Metal Selection and Surface Characteristics. In: Branemark P-I, Zarb GA, Albrektsson T. Tissure-Integrated Prostheses. Chicago: Quintesson Publishing Co., Inc, 1985:99-116
[85]梁芳慧，周廉．钛和钛合金生物活化研究现状．稀有金属材料与工程，2003，32(4)：241-245
[86]H. M. Kim, F. Miyaji, T. Kokubo, et al. Adhesive strength of bonelike apatiteto chemically treated titanium. Bioceramies, Volume 9. Proceeding of the 9th International Symposium on Ceramics in Medicine. Japan: 1996, 301-304
[87]杨贤金，朱胜利，崔振铎，等．NiTi合金表面化学沉积羟基磷灰石生物活性层机理的研究．功能材料，2001，32(2)：154-155
[88]高家诚，王勇，张春艳，等．TC4表面液相沉积生物陶瓷涂层的研究． 功能材料，2002，33(4)：456-458
[89]张小明．通过化学处理制备梯度功能生物活性钛及钛合金．钛工业进展，1999，4：31-32
[90]李德华．医用钛表面的微观改造．国外医学生物医学工程分册，1997，20(1)：24-27
[2]顾汉卿．生物医学材料的现状及发展(一)．中国医疗器械信息，2001，7(1)：45-48
[3]高景恒．加速我国医用生物材料的研究与开发．实用美容整形外科杂志，1998，9(3)：113-114
[4]杨国营．生物医用材料．河北化工，2002，4：17-19
[5]田文华．生物材料和医用植入物科学——现在和未来展望．国外医学生物医学工程分册，1997，20(4)：253-256
[6]李世普．生物医用材料导论．湖北：武汉工业大学出版社，2000．8
[7]俞耀庭，张兴栋．生物医用材料．天津：天津大学出版社．2000．12
[8]Yanashitak U. Immobilization of yeast cell in porous silica carrier with Sol-Gel process. J Ceram Society Japan, 1992, 100.. 426-429
[9]Song C X, Labhasetwar V, Murphy H, et al. Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery. J Controlled Rellease, 1997, 43: 197-212
[10]Poggie RA, Kovacs P, Davidson JA. Oxygen diffusion hardening of Ti-Nb-Zr alloys. Mater Manuf Processes, 1996, 11 (2): 185-197
[11]崔福斋，冯庆玲．生物材料学．北京：科学出版社．1997．6
[12]杨晓芳，奚廷斐．生物材料生物相容性评价研究进展．生物医学工程学杂志，2001，18(1)：123-128
[13]TC150LS05832. Implants for Surgery-Metallic Materials, Part1-12, 1999
[14]Ninomi M, Kuroda D,Fukunaga K, et al. Corrosion wear fracture of new β type biomedical titanium alloys[J]. Mater Sci Eng, 1999, A263:193-199
[15]阮建明，Grant M H，黄伯云．金属毒性研究(Ⅰ)[J]．中国有色金属学报，2001，11(6)：960-965
[16]阮建明，Grant M H，黄伯云．金属毒性研究(Ⅱ)[J]．中国有色金属学报，2002，12(1)：14-19
[17]Kathy Wang. The use of titaniumfor medicalapplicationsinthe USA. Mater. Sci. and Eng., 1996, A213: 134-137
[18]佐佐木 佳男，松下富春．人工骨关节用新二合金金属，1996，66(19)：64-69
[19]宁聪琴，周玉．医用钛合金的发展及研究现状．材料科学与工艺，2002，10(1)：100-106
[20]Tengvall P, Lundstrom I. Physico-chemical considerations of titanium as a biomaterial [J]. Clin Mater, 1992, 9:115-134
[21][英]威廉姆斯 D F主编，朱鹤孙等译．医用与口腔材料．见：卡恩R W，哈森P，克雷默E J主编．材料科学与技术丛书．北京：科学出版社，1999．29-63
[22]Parks G A. The isoelectric point of solid oxides, solid hydroxides, and aqueous hydroxy complex system [J]. ChemRev, 1965, 65:177-198
[23]HenchLL. Bioceramic: from concept to clinic [J]. JAmCeram Soc, 1991, 74:1487-1510
[24]Kokubo T. Bioactive glass-ceramics: properties and applications [J]. Biomaterials, 1991, 12: 155-163
[25]Li P, Kangasniemi I, De Groot K, et al. Bone like hydroxyapatite induction by a gel-derived titania on atitanium substrate [J]. J Am Ceram Soc, 1994, 77:1307-1312
[26]FendorfM, Gronsk R. Surface precipitation reaction on oxide surfaces [J]. J Colloid Interface Sci, 1992, 148:295-298
[27]Bruneel N, Helsen J. In-vitro simulation of biocompatibility of titanium [J]. J Biomed Mater Res, 1988, 22:203-214
[28]程奎，翁文剑，葛曼珍．生物陶瓷涂层[J]．材料科学与工程，1998，16(3)：8-12
[29]陈安玉．口腔种植学[M]．成都：四川科学技术出版社，1991．64
[30]Rostlund T, Mckellop H, Albrektsson B, et al. Wear of ion implanted pure titanium against UHMWPE [J]. Biomaterials, 1989, 10:176-181
[31]Perry A. Ion implantation of titanium alloys for biomaterial and other applications[J]. Surf Eng, 1987, 3: 154-159
[32]Mohammadi S, Wictorin L, Ericsonetal L E. Cast titanium as implant material. J Mater. Sci. : Mater Med., 1995, 6:435-444
[33]Ungersboeck A, Geret V, Pohler O, et al. Tissure reaction to bone plates made of pure titanium: a prospective, quantitative clinicalstudy. J. Mater. Sci. : Mater Med., 1995, 6:223-229
[34]Reis R L, Monteiro F J, Hastings G W. Stability of hydroxyapatite plasma-sprayed coated Ti-6A1-4V under cyclic bending in simulated physiological solutions. J Mater. Sci.: Mater Med., 1994, 5:457-462
[35]Gross K A , Berndt C C. In vitro testing of plasma sprayed hydroxyapatite
coatings. J. Mater. Sci.: Mater Med., 1995, 6:214-219
[36]Ong J L, Lucas L C. Post-deposition heat treatments for ion beam sputter deposited calcium phospate coatings [J]. Biomaterials, 1994, 15 (15): 337-341
[37]Ellies L G, Nelson D G A, Featherstone J D B. Crystallographic changes in calcium phosphates during plasma-spraying [J]. Biomaterials, 1992, 13 (5): 313-317
[38]储成林，朱景川，尹钟大，等．医用钛合金及其表面改性．材料科学与工艺，1998，6(2)：40-44
[39]Chang B, Chang W K, Wang B C, et al. Plasma spraying of zirconia-reinforced hydroxyapatite composite coatings on titanium : Part Ⅰ phase microstructure and bonding strength. J. Mater. Sci.: Mater Med., 1997, 8:193-200
[40]Chang B, Chang W K, Wang B C, et al. Plasma spraying of zirconia-reinforced hydroxyapatite composite coatings on titanium: Part Ⅱ dissolution behaviour in simulated body fludi and bonding degradation. J. Mater. Sci.: Mater Med., 1997, 8:201-211
[41]Chernlin J H, Liu M L, Ju C P. Structure and properties of hydroxyapatite-bioactive glass composites plasma sprayed on Ti6Al4V. J. Mater. Sci.: Mater Med., 1994, 5:279-283
[42]曾晟宇，赵乃勤，崔振铎，等．金属生物材料表面改性研究的进展．材料保护，2000，33(1)： 5-8
[43]Olbrich Kevin C, Andersen Thomas T, Blumenstock Frank A, et al. Surfaces modified with covalently-immobilized adhesive peptides affect fibroblast population motility[J]. Biomaterials, 1996, 17 (8): 759-764
[44]Narayan J, Fan W D, Narayan R J, et al. Diomond, diamone-like and titanium nitride biocompatible coatings for human body parts. Mater. Sci. and Eng., 1994, B25:5-10
[45]Grant D M, Lo W J, Parker K G, et al. Biocompatible and mechanical properties of low temperature deposited quaternary (Ti, AI, V, N) coatings on Ti6AI4V titanium alloy substrates
[46]金自宜．钛系生物医学工程材料．材料导报，1993，2：18-23
[47]冯颖芳，康浩方，张震．钛合金医用植入物材料的研究及应用．稀有金属，2001，25(5)：349-354
[48]劳金海．钛在生物医学中应用的新发展．上海钢研，2001，4：60-62
[49]冈崎义光．各种金属细胞适合性生体用新合金开发，1998，37(10)：838-842
[50]槁隆夫．金属系生体材料表面改质． 1998，37(10)：853-855
[51]金铉敏，宫路史明，小久保正．化学处理倾斜机能生体活性合金调制．日本金属学会志，1998，62(11)：1102-1107
[52]野浪亨，长沼胜义，龟山哲也．超塑性利用生体用合金的接合．1998，37(10)：856-858
[53]Thomas K A, Kay J F, Cook S D, et al. The effect of surface macrotexture and hydroxylapatite coating on the mechanical strengths and histologic profiles of titanium implant materials. J Biomed Mater Res, 1987, 21:1395
[54]周彦邦．钛合金铸造概论．北京：航空工业出版社，2000．2
[55]Kokubo T. Bioactivity of glass and glasses-ceramics. In: Ducheyne P, Kokubo T, Blitterswijk CA, editors. Handbook of bioactive ceramics, Vol. 1: bone-bonding biomaterials, Reed healthcare communications. The Netherlands: Leiden, 1992, 31-46
[56]Kokubo T, Ito S, Huang Z T, et al. Ca, P-rich layer formed on high-strength bioactive glass-ceramic A-W . J Biomed Mater Res, 1990, 24:331-343
[57]Kokubo T, Kushitani H, Sakka S, et al. Solution able to reproduce in vivo surface-structure changes in bioactive glass-ceramics A-W. J Biomed Mater Res, 1990, 24: 721-734
[58]《有色金属提取冶金手册》编辑委员会．有色金属提取冶金手册，稀有高熔点金属(上)，北京：冶金工业出版社，1999
[59]Song Y, Xu D S, Yang R, et al. Theoretical study of the effects of alloying elements on the strength and modulus of β -type bio-titanium alloys. Mater. Sci. Eng, 1999, A260: 269-274
[60]1986. 45
[61]侯增寿，卢光熙．金属学原理．上海：上海科学技术出版社。1998．3
[62][苏]E．A．鲍利索娃等著，陈石卿译．钛合金金相学．北京：国防工业出版社．1986．4
[63]李晓娥，祖庸．液相法合成纳米二氧化钛[J]．钛工业进展，1997，3：14-17
[64]Amarchand S, Rama Mohan T R, Ramakrishnan P. A novel chemical solution technique for the preparation of nano size titanium powders from titanium dioxide [J]. Advanced Powder Technology, 2000, 11 (4): 415-422
[65]高晓云，张敬畅，王伟洁，等．激光热解法制备TiO_2超微粉[J]．无机材料学报，1993，8(1)： 57-62
[66]李学富．超微细二氧化钛——中高功能化新型无机材料[J]．化工新型材料，1995，23(5)：36-38
[67]李燕．醇—水溶液加热法制备纳米级二氧化钛超细粉[J]．陶瓷学报，2000，21(1)：51-53
[68]张敬畅，曹微良，于定新，等．超临界流体干燥法制备纳米级TiO_2的研究[J]．无机材料学报，1999，14(1)：29-35
[69]周芝骏等编．钛的性质及其应用．北京：高等教育出版社，1993．27-35
[70]张仲燕，邢建南，施利毅，等．纳米二氧化钛颗粒的制备[J]．上海大学学报(自然科学版)，2002，8(1)：87-90
[71]刘河洲．纳米TiO_2的反胶束水解合成与热处理过程动力学研究．上海交通大学博士论文，2000：38-42
[72]陈吉华，杨大智，刘敬肖，等．Ti-Ta-O复合薄膜的制备及抗腐蚀性．材料研究学报，2001，15(5)：587-592
[73]王浩，赵文宽，方佑龄，等．二氧化钛光催化杀灭肿瘤细胞的研究．催化学报，1999，20(3)：373-374
[74]孙康．钛提取冶金物理化学．北京：冶金工业出版社，2001．11
[75]Chen Shihai, Zhang Hongzhi. Oxidation Principle of Metals. Shenyang: Northeastern University Press, 1988:1-16
[76]Zhai Jinkun. High Temperature Corrosion of Metals. Beijing: Beijing Aeronautics & Astronautics University Press, 1994:35-52
[77]冉均学．钛基生物医用材料表面改性及模拟体液培养．河北工业大学硕士论文，2003：32-33
[78]Takadama H, Kim H M, Kokubo T and Nakamura T. XPS study of the process of apatite formation on bioactive Ti-6A1-4V alloy in simulated body fluid. Science and Technology of Advanced Materials, 2001, 2: 389-396
[79]储成林，朱景川，尹钟大，等．HA-Ti/Ti/HA-Ti轴对称生物功能梯度材料的制备及其热应力缓和特性．中国有色金属学报，1999，9(1)：57-62
[80]石玉龙，谢广文．二氧化钛的用途及其薄膜的制备方法．电机电器技术，2000，3：37-41
[81]张峰，李昌荣，王向晖，等．氧化钛薄膜的血液相容性机理探讨．生物医学工程学杂志．2000，17(2)： 146-150
[82]陈俊英，杨萍，冷永祥，等．掺杂氧化钛薄膜的制备与血液相容性研究．功能材料，2000，31(2)： 212-214
[83]黄楠，杨萍，曾小兰，等．Ti-O／Ti-N复合薄膜的离子束合成及人工心脏瓣膜材料表面改性研究，功能材料与器件学报，1997，3(1)：40-46
[84]Kasem O, Band Lausma. J. Metal Selection and Surface Characteristics. In: Branemark P-I, Zarb GA, Albrektsson T. Tissure-Integrated Prostheses. Chicago: Quintesson Publishing Co., Inc, 1985:99-116
[85]梁芳慧，周廉．钛和钛合金生物活化研究现状．稀有金属材料与工程，2003，32(4)：241-245
[86]H. M. Kim, F. Miyaji, T. Kokubo, et al. Adhesive strength of bonelike apatiteto chemically treated titanium. Bioceramies, Volume 9. Proceeding of the 9th International Symposium on Ceramics in Medicine. Japan: 1996, 301-304
[87]杨贤金，朱胜利，崔振铎，等．NiTi合金表面化学沉积羟基磷灰石生物活性层机理的研究．功能材料，2001，32(2)：154-155
[88]高家诚，王勇，张春艳，等．TC4表面液相沉积生物陶瓷涂层的研究． 功能材料，2002，33(4)：456-458
[89]张小明．通过化学处理制备梯度功能生物活性钛及钛合金．钛工业进展，1999，4：31-32
[90]李德华．医用钛表面的微观改造．国外医学生物医学工程分册，1997，20(1)：24-27