Development of high biocompatible titanium alloys for medical and welfare applications

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，设计了具有低杨氏模量、高强度和高可加工性的新型生物医用β型钛合金。采用d电子合金设计方法设计了Ti-29Nb-13Ta、Ti-29Nb-13Ta-4.6 zr、Ti-16Nb-13Ta-4Mo、Ti-29Nb-13Ta- 2sn、Ti-29Nb-13Ta-4.6 sn和Ti-29Nb-12Ta-6Sn。将设计的合金制作成45g的小铸锭，在实验室进行热处理，并对合金的塑性加工性和基本力学性能进行了评价。每种合金都可以完全满足生物医学应用的目标性能，但Ti-29Nb- 13Ta-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来看，Ti-29Nb-13Ta-4.6Zr…More有望具有优异的生物相容性。然后用l929细胞评价Ti-29Nb-13Ta-4.6Zr的细胞毒性。该合金的细胞毒性与纯钛相似。因此，决定对Ti-29Nb-13Ta-4.6Zr进行进一步的实用化评价。第一步是制作实用型钢锭。采用感应熔炼法和悬浮熔炼法成功地制备了均质实用水平钢锭。对实用级钢锭进行了热处理，并对热处理后的钢锭力学性能进行了评价。固溶后时效处理，或冷轧后直接时效处理，使Ti-29Nb-13Ta-4.6Zr的强度和塑性与Ti-6Al-4V ELI等效平衡，保持低模量。然后，在模拟车身环境中评估Ti-29Nb-13Ta-4.6Zr的磨损特性。以氧化锆为配合材料时，Ti-29Nb-13Ta-4.6Zr的耐磨性大于Ti-6Al-4V ELI或SUS 316l不锈钢的耐磨性，而以氧化铝为配合材料时则相反。因此，为了提高Ti-29Nb-13Ta-4.6Zr的耐磨性，有必要进行表面处理。氧化处理可有效提高Ti-29Nb-13Ta-4.6Zr的耐磨性。通过固溶和时效处理，Ti-29Nb-13ta-4.6Zr的疲劳强度得到了很大的提高，与Ti-6Al-4V ELI相当。Ti-29Nb-13Ta-4.6Zr的疲劳比大于常规β型钛合金，与常规α+ β型生物医用钛合金相当。Ti-29Nb-13Ta-4.6Zr微动疲劳强度明显小于普通疲劳强度，但与常规医用钛合金相当。在Ti-29Nb-13Ta-4.6Zr合金中，微动引起的疲劳强度下降相对较小。与纯钛或Ti-6Al-4V相比，Ti-29Nb-13Ta-4.6Zr在空气中更容易形成磷酸盐钙结晶玻璃。将Ti-29Nb-13Ta-4.6Zr、Ti-6Al-4V和SUS 316L不锈钢植入兔脊柱附近肌肉，观察肌肉组织变化。每块肌肉组织几乎都是一样的。因此，Ti-29Nb-13Ta-4.6Zr具有良好的生物相容性。从上述结果来看，Ti-29Nb-13Ta-4.6Zr有望投入实际应用。为了使Ti-29Nb-13Ta-4.6Zr的实际应用，需要通过微观组织控制来进一步发展其力学性能，建立表面处理以提高耐磨性，进一步评估模拟体环境下的疲劳强度和微动疲劳强度，用活体验证低模量的有效性，并进行更大动物的生物相容性试验。此外，还需要对合金进行临床试验。Ti-29Nb-132Ta-4.6Zr也有望应用于牙科产品。因此，Ti-29Nb-13Ta-4.6Zr在牙科领域的实用化备受期待。少

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