Development of high biocompatible titanium alloys for medical and welfare applications

开发用于医疗和福利应用的高生物相容性钛合金

• 批准号: 10555231
• 负责人: NIINOMI Mitsuo
• 金额: $ 7.94万
• 依托单位: Toyohashi University of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10555231/
• 关键词: Biomedical titanium alloy; Ti-29Nb-13Ta-4.6Zr alloy; Low Young's modulus; Biocompatibility; Cyto-toxicity; Mechanical properties; Fatigue characteristics; Friction wear characteristics; 高生体適合性; 生体用材料; β型チタン合金; 医療・福祉; 加工熱処理; ミクロ組織; 力学的生体融合性 /

According to the data on cytotoxicity of pure metals and representative metallic biomaterials, non-toxic elements Nb, Ta, Zr, Mo and Sn were selected as alloying elements for designing new β type titanium alloys for biomedical applications with low Young's modulus, high strength and high workability. Ti-29Nb-13Ta, Ti-29Nb-13Ta-4.6Zr, Ti-16Nb-13Ta-4Mo, Ti-29Nb-13Ta-4Mo, Ti-29Nb-13Ta-2Sn, Ti-29Nb-13Ta-4.6Sn and Ti-29Nb-12Ta-6Sn were designed using d-electron alloy design method. Small ingots of designed alloys with a weight of 45g were fabricated followed by thermomechanical treatments in the laboratory, and plastic workability and basic mechanical properties of the alloys were then evaluated. Every alloy could be expected to full fill the target performance for biomedical applications, but Ti-29Nb- 13Ta-4.6Zr was found to easily satisfy the balance of strength, elongation and Young's modulus. Furthermore, judging from the data on the cytotoxicity of alloying elements, Ti-29Nb-13Ta-4.6Zr … More was expected to be excellent in biocompatibility. Then, the cytotoxicity of Ti-29Nb-13Ta-4.6Zr was evaluated using L 929 cells. Cytotoxicity of this alloy was similar to that of pure titanium.Therefore, the further evaluation for practical use was determined to be carried out on Ti-29Nb-13Ta-4.6Zr. For the first step, practical level ingot was fabricated. The homogeneous practical level ingot was successfully fabricated by induction melting method or levitation melting method. Thermomechanical treatments were carried on the practical level ingot, and then mechanical properties of the thermomechanical treated ingot were evaluated. Solution treatment followed by aging, or direct aging after cold rolling gave Ti-29Nb-13Ta-4.6Zr qeuivalent balance of strength and ductility to that of Ti-6Al-4V ELI with keeping low modulus. Then, wear characteristics of Ti-29Nb-13Ta-4.6Zr were evaluated in simulated body environment. The wear resistance of Ti-29Nb-13Ta-4.6Zr was greater than that of Ti-6Al-4V ELI or SUS 316 L stainless steel when zirconia was used as a mating material, but opposite trend was observed when alumina was used as a mating material. Therefore, it was concluded that the surface treatment was necessary to improve the wear resistance of Ti-29Nb-13Ta-4.6Zr. Oxidation treatment was found to be effective to improve the wear resistance of Ti-29Nb-13Ta-4.6Zr. The fatigue strength of Ti-29Nb-13ta-4.6Zr was improved very much by conducting solutionizing and aging, and was equal to that of Ti-6Al-4V ELI.The fatigue ratio of Ti-29Nb-13Ta-4.6Zr was greater than that of conventional β type titanium alloy, and was equivalent to that of conventional α+ β type biomedical titanium alloys. Fretting fatigue strength of Ti-29Nb-13Ta-4.6Zr was significantly smaller than that of plain fatigue strength, but *quivalent to that of conventional biomedical titanium alloys. The decrease in fatigue strength due to fretting was relatively smaller in Ti-29Nb-13Ta-4.6Zr.Phosphate calcium crystallized glass could be easily formed on Ti-29Nb-13Ta-4.6Zr in air comparing with the case of pure titanium or Ti-6Al-4V.Biocompatibility of Ti-29Nb-13Ta-4.6Zr was significantly improved by this surface coating of phosphate calcium, crystallized glass.Ti-29Nb-13Ta-4.6Zr, Ti-6Al-4V and SUS 316L stainless steel were implanted in the muscle near the spine of the rabbit, and then the muscle tissue change was examined. Each muscle tissue was nearly the same. Therefore, the biocompatibility of Ti-29Nb-13Ta-4.6Zr was found to be excellent.From the results mentioned above, Ti-29Nb-13Ta-4.6Zr is strongly expected to be put into practical use. In order to put Ti-29Nb-13Ta-4.6Zr into practical use, further development in mechanical properties by microstructural control, establishment of surface treatment to improve the wear resistance, further evaluation of fatigue strength and fretting fatigue strength in simulated body environment, verifying the effectiveness of low modulus using living body, and biocompatibility test using bigger animals are needed. Furthermore clinical tests of the alloy is needed. Ti-29Nb-132Ta-4.6Zr is also expected to be applied for dental products. Therefore, the practical use of Ti-29Nb-13Ta-4.6Zr is highly expected in dental field. Less

根据纯金属和代表性金属生物材料的细胞毒性数据，选择无毒元素Nb、Ta、Zr、Mo和Sn作为合金元素，设计出低杨氏模量、高强度和高加工性能的新型生物医用β型钛合金。采用d电子合金设计方法设计了Ti-29 Nb-13 Ta、Ti-29 Nb-13 Ta-4.6Zr、Ti-16 Nb-13 Ta-4 Mo、Ti-29 Nb-13 Ta-4 Mo、Ti-29 Nb-13 Ta-2Sn、Ti-29 Nb-13 Ta-4.6Sn和Ti-29 Nb-12 Ta-6Sn合金。在实验室中制备了45 g的设计合金的小锭，然后进行形变热处理，然后评价合金的塑性加工性和基本机械性能。可以预期每种合金都能完全满足生物医学应用的目标性能，但发现Ti-29 Nb-13 Ta-4.6Zr很容易满足强度、伸长率和杨氏模量的平衡。此外，从合金元素的细胞毒性数据判断，Ti-29 Nb-13 Ta-4.6Zr ...更多信息 预期生物相容性优异。然后，使用L 929细胞评价Ti-29 Nb-13 Ta-4.6Zr的细胞毒性。该合金的细胞毒性与纯钛相似，因此，确定对Ti-29 Nb-13 Ta-4.6Zr进行进一步的实际应用评价。第一步，制造实用级铸锭。采用感应熔炼法和悬浮熔炼法成功地制备出了均匀的实用水平铸锭。对实用级铸锭进行形变热处理，并对形变热处理后铸锭的力学性能进行评价。Ti-29 Nb-13 Ta-4.6Zr固溶后再时效或冷轧后直接时效，在保持低模量的同时，强度和塑性达到与Ti-6Al-4V ELI相当的平衡。然后，在模拟人体环境中评价Ti-29 Nb-13 Ta-4.6Zr的磨损特性。当以ZrO 2为配副材料时，Ti-29 Nb-13 Ta-4.6Zr的耐磨性高于Ti-6Al-4V ELI或SUS 316 L不锈钢，而以Al 2 O3为配副材料时，Ti-29 Nb-13 Ta-4.6Zr的耐磨性低于Ti-6Al-4V ELI或SUS 316 L不锈钢。因此，表面处理是提高Ti-29 Nb-13 Ta-4.6Zr耐磨性的必要措施。氧化处理可有效提高Ti-29 Nb-13 Ta-4.6Zr合金的耐磨性。Ti-29 Nb-13 Ta-4.6Zr合金经固溶时效处理后，疲劳强度显著提高，与Ti-6Al-4V ELI相当，疲劳比大于常规β型钛合金，与常规α+ β型生物医用钛合金相当。Ti-29 Nb-13 Ta-4.6Zr的微动疲劳强度明显低于普通疲劳强度，但与常规生物医用钛合金相当。Ti-29 Nb-13 Ta-4. 6 Zr的微动疲劳强度下降较小，与纯钛或Ti-6Al-4V相比，Ti-29 Nb-13 Ta-4. 6 Zr在空气中容易形成磷酸钙微晶玻璃，这种磷酸钙涂层显著改善了Ti-29 Nb-13 Ta-4. 6 Zr的生物相容性，将Ti-29 Nb-13 Ta-4.6Zr、Ti-6Al-4V和SUS 316L不锈钢植入家兔脊柱附近的肌肉中，然后观察肌肉组织的变化。每一个肌肉组织几乎都是一样的。因此，Ti-29 Nb-13 Ta-4.6Zr合金具有良好的生物相容性，具有很好的应用前景。为了使Ti-29 Nb-13 Ta-4.6Zr合金投入实际应用，需要通过微观组织控制进一步提高力学性能，建立提高耐磨性的表面处理，进一步评估模拟人体环境下的疲劳强度和微动疲劳强度，使用活体验证低模量的有效性，以及使用更大动物进行生物相容性试验。此外，还需要对该合金进行临床试验。Ti-29 Nb-132 Ta-4.6Zr也有望应用于牙科产品。因此，Ti-29 Nb-13 Ta-4.6Zr合金在牙科领域的应用前景十分广阔。少

项目成果

M.Niinomi: "Development of Titanium Alloys Composed of Non-toxic Elements with Low Modulus and High Strength for Biomedical Applications"Transaction of the Sixth World Biomaterials Congress. 1359 (2000)

M.Niinomi：“开发用于生物医学应用的由无毒元素组成的低模量和高强度钛合金”第六届世界生物材料大会的交易。

D.Kuroda et al.: "Design and Mechanical Properties of New β Type Titanium Alloys for Implant Materials" Materials Science and Engineering. A243. 244-249 (1998)

D.Kuroda 等人：“用于植入材料的新型 β 型钛合金的设计和机械性能”材料科学与工程 244-249 (1998)。

M.Niinomi: "Recent Research and Development of Tianium for Biomedical Applications in Japan"JOM. 51巻6号. 32-34 (1999)

M. Niinomi：“日本生物医学应用钛的最新研究和开发”JOM，第 51 卷，第 6 期。32-34 (1999)

M.Niinomi et al.: "Development of β Type Titanium Alloys for Hard Tissue Replacing Materials" Proc.SSAM-4. 365-368 (1998)

M. Niinomi 等人：“用于硬组织替代材料的 β 型钛合金的开发”Proc.SSAM-4 (1998)。

M.Niinomi: "Mechanical Properties of Biomedical Titanium Alloys"Materials Science and Engineering A. A243. 231-236 (1998)

M.Niinomi：《生物医用钛合金的力学性能》材料科学与工程A.A243。