新型医用钛合金Ti-25Nb-10Ta-1Zr-0.2Fe（TNTZ）的生物相容性研究
发布时间：2018-10-15 17:38
【摘要】：背景：本项目研究的Ti-25Nb-10Ta-1Zr-0.2Fe(下文简称TNTZ)合金是由中南大学材料学院易丹青课题组设计研发的新型β型医用钛合金,已申请专利。由于其弹性模量比目前临床上应用的钛合金更接近于人体骨骼,并且不含对人体有害的金属元素,故而在临床上有着广泛的应用前景。目前国内对于TNTZ的研究主要集中于材料专业,例如对其耐磨性、疲劳性、硬度及弹性等特性的测试,然而对其生物学安全性却未见全面的研究报道。本实验采用体外实验与动物实验相结合,从细胞、血液、组织三个层面检测这种新型材料的生物相容性,以全面评价新型钛合金的生物安全性,为其临床应用提供参考。目的：测定新型β型钛合金Ti-25Nb-10Ta-1Zr-0.2Fe(TNTZ)的生物相容性,为其医学应用提供实验数据。 方法： 1.参照国家标准GB／T16886.4-2003／IS010993-4：2002医疗器械生物学评价第四部分：与血液相互作用试验,用体外直接接触法,将5g合金放入恒温稀释兔血样品中1h后,用分光光度计测定实验金属的溶血率。 2.参照国家标准GB／T16886.5-2003／IS010993-5：1999医疗器械生物学评价第五部分：体外细胞毒性试验,用合金浸提液培养L929细胞,测定实验金属的毒性等级,分别采用光学显微镜下观察细胞形态、MTT法检测增殖率及流式细胞术检测细胞周期3种方法。 3.参照国家标准GB／T16886.6-1997／IS010993-6：1994医疗器械生物学评价第六部分：植入后局部反应试验,用局部植入法测定实验金属的体内毒性。将直径2mm,长6mm的圆柱状合金样品植入新西兰兔股骨,分别于术后4周、12周、26周处死一组动物,采集标本。 4.用普通X光机拍摄观察金属对植入骨骨质的影响。 5.制作脱钙切片和不脱钙超硬组织切片,观察合金对周围骨质是否有炎症、坏死、肿瘤等不良影响。 结果： 1. TNTZ的溶血率为2.3%,低于国家使用标准(5%)。 2. TNTZ不影响L929细胞的形态,各实验组细胞形态及数量相仿,细胞呈梭形或多角形,有伪足伸出。TNTZ组的MTT值为1.031±0.059, S期比率为40.32±5.49,与对照组比较均无统计学差异(P0.05),细胞毒性为0级。 3. TNTZ植入兔股骨后未影响创口愈合,未引起炎症、肿瘤,种植体-骨组织界面紧密贴合,无溶骨现象出现,对实验动物无毒性作用。 结论： 1. TNTZ基本无溶血作用,无细胞毒性,对实验动物无不良影响,符合国家使用标准。 2. TNTZ与骨的结合只是单纯的接触,无骨性结合,生物应用前应继续研究其表面处理与活化,提高与人体的适应性。
[Abstract]:Background: the Ti-25Nb-10Ta-1Zr-0.2Fe (hereinafter referred to as TNTZ) alloy studied in this project is a new type 尾-type medical titanium alloy designed and developed by Yi Danqing Research Group of the School of Materials of Central South University. It has applied for patent. Because its modulus of elasticity is closer to the human skeleton than the titanium alloy which is used in clinic at present, and does not contain any metal elements harmful to human body, it has a wide application prospect in clinic. At present, the research on TNTZ is mainly focused on the material specialty, such as the testing of wear resistance, fatigue, hardness and elasticity, etc. However, there is no comprehensive research report on the biological safety of TNTZ. In this experiment, the biocompatibility of the new material was tested from three aspects of cell, blood and tissue, in order to evaluate the biological safety of the new titanium alloy and provide reference for its clinical application. Objective: to determine the biocompatibility of 尾-titanium alloy Ti-25Nb-10Ta-1Zr-0.2Fe (TNTZ) and provide experimental data for its medical application. Methods: 1. Biological evaluation of GB/T16886.4-2003/IS010993-4:2002 medical devices with reference to national standard part 4: interaction test with blood, 5g alloy was put into rabbit blood samples at constant temperature for 1 h by direct contact method in vitro. Determination of hemolysis rate of experimental metals by spectrophotometer. 2. 2. Biological evaluation of GB/T16886.5-2003/IS010993-5:1999 medical devices with reference to national standard part 5: in vitro cytotoxicity test, L929 cells were cultured with alloy extract, and the toxic grade of experimental metals was determined. The cell morphology was observed under optical microscope, the proliferation rate was detected by MTT assay and the cell cycle was detected by flow cytometry. According to the national standard GB/T16886.6-1997/IS010993-6:1994 medical device biological evaluation part 6: local reaction test after implantation the in vivo toxicity of experimental metal was determined by local implantation method. A 2 mm long 6mm alloy was implanted into the femur of New Zealand rabbits. A group of animals were killed at 4 weeks, 12 weeks and 26 weeks after operation. The effect of metal on bone graft was observed by X-ray camera. 5. 5. Decalcified sections and undecalcified superhard tissue sections were made to observe the adverse effects of the alloy on the surrounding bone such as inflammation necrosis tumor and so on. Results: 1. The hemolysis rate of TNTZ was 2.3%, which was lower than the national standard (5%). TNTZ did not affect the morphology of L929 cells. The cells in each experimental group were similar in shape and number, and the cells were spindle or polygonal. The MTT value and S phase ratio of TNTZ group were 1.031 卤0.059 and 40.32 卤5.49 respectively, which were not significantly different from those of control group (P0.05). TNTZ implantation of femur did not affect wound healing, did not cause inflammation, tumor, implant-bone tissue interface close, no osteolysis phenomenon, no toxic effect to experimental animals. Conclusion: 1. TNTZ basically has no hemolysis, no cytotoxicity, no adverse effects on experimental animals, and conforms to the national standard of use. 2. The combination of TNTZ and bone is only simple contact, no osseous binding, the biological application should continue to study its surface treatment and activation, and improve the adaptability to human body.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08
本文编号：2273299
[Abstract]:Background: the Ti-25Nb-10Ta-1Zr-0.2Fe (hereinafter referred to as TNTZ) alloy studied in this project is a new type 尾-type medical titanium alloy designed and developed by Yi Danqing Research Group of the School of Materials of Central South University. It has applied for patent. Because its modulus of elasticity is closer to the human skeleton than the titanium alloy which is used in clinic at present, and does not contain any metal elements harmful to human body, it has a wide application prospect in clinic. At present, the research on TNTZ is mainly focused on the material specialty, such as the testing of wear resistance, fatigue, hardness and elasticity, etc. However, there is no comprehensive research report on the biological safety of TNTZ. In this experiment, the biocompatibility of the new material was tested from three aspects of cell, blood and tissue, in order to evaluate the biological safety of the new titanium alloy and provide reference for its clinical application. Objective: to determine the biocompatibility of 尾-titanium alloy Ti-25Nb-10Ta-1Zr-0.2Fe (TNTZ) and provide experimental data for its medical application. Methods: 1. Biological evaluation of GB/T16886.4-2003/IS010993-4:2002 medical devices with reference to national standard part 4: interaction test with blood, 5g alloy was put into rabbit blood samples at constant temperature for 1 h by direct contact method in vitro. Determination of hemolysis rate of experimental metals by spectrophotometer. 2. 2. Biological evaluation of GB/T16886.5-2003/IS010993-5:1999 medical devices with reference to national standard part 5: in vitro cytotoxicity test, L929 cells were cultured with alloy extract, and the toxic grade of experimental metals was determined. The cell morphology was observed under optical microscope, the proliferation rate was detected by MTT assay and the cell cycle was detected by flow cytometry. According to the national standard GB/T16886.6-1997/IS010993-6:1994 medical device biological evaluation part 6: local reaction test after implantation the in vivo toxicity of experimental metal was determined by local implantation method. A 2 mm long 6mm alloy was implanted into the femur of New Zealand rabbits. A group of animals were killed at 4 weeks, 12 weeks and 26 weeks after operation. The effect of metal on bone graft was observed by X-ray camera. 5. 5. Decalcified sections and undecalcified superhard tissue sections were made to observe the adverse effects of the alloy on the surrounding bone such as inflammation necrosis tumor and so on. Results: 1. The hemolysis rate of TNTZ was 2.3%, which was lower than the national standard (5%). TNTZ did not affect the morphology of L929 cells. The cells in each experimental group were similar in shape and number, and the cells were spindle or polygonal. The MTT value and S phase ratio of TNTZ group were 1.031 卤0.059 and 40.32 卤5.49 respectively, which were not significantly different from those of control group (P0.05). TNTZ implantation of femur did not affect wound healing, did not cause inflammation, tumor, implant-bone tissue interface close, no osteolysis phenomenon, no toxic effect to experimental animals. Conclusion: 1. TNTZ basically has no hemolysis, no cytotoxicity, no adverse effects on experimental animals, and conforms to the national standard of use. 2. The combination of TNTZ and bone is only simple contact, no osseous binding, the biological application should continue to study its surface treatment and activation, and improve the adaptability to human body.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08
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