發(fā)布時間：2018-10-15 17:38

【摘要】：背景：本項目研究的Ti-25Nb-10Ta-1Zr-0.2Fe(下文簡稱TNTZ)合金是由中南大學(xué)材料學(xué)院易丹青課題組設(shè)計研發(fā)的新型β型醫(yī)用鈦合金,已申請專利。由于其彈性模量比目前臨床上應(yīng)用的鈦合金更接近于人體骨骼,并且不含對人體有害的金屬元素,故而在臨床上有著廣泛的應(yīng)用前景。目前國內(nèi)對于TNTZ的研究主要集中于材料專業(yè),例如對其耐磨性、疲勞性、硬度及彈性等特性的測試,然而對其生物學(xué)安全性卻未見全面的研究報道。本實驗采用體外實驗與動物實驗相結(jié)合,從細胞、血液、組織三個層面檢測這種新型材料的生物相容性,以全面評價新型鈦合金的生物安全性,為其臨床應(yīng)用提供參考。目的：測定新型β型鈦合金Ti-25Nb-10Ta-1Zr-0.2Fe(TNTZ)的生物相容性,為其醫(yī)學(xué)應(yīng)用提供實驗數(shù)據(jù)。 方法： 1.參照國家標準GB／T16886.4-2003／IS010993-4：2002醫(yī)療器械生物學(xué)評價第四部分：與血液相互作用試驗,用體外直接接觸法,將5g合金放入恒溫稀釋兔血樣品中1h后,用分光光度計測定實驗金屬的溶血率。 2.參照國家標準GB／T16886.5-2003／IS010993-5：1999醫(yī)療器械生物學(xué)評價第五部分：體外細胞毒性試驗,用合金浸提液培養(yǎng)L929細胞,測定實驗金屬的毒性等級,分別采用光學(xué)顯微鏡下觀察細胞形態(tài)、MTT法檢測增殖率及流式細胞術(shù)檢測細胞周期3種方法。 3.參照國家標準GB／T16886.6-1997／IS010993-6：1994醫(yī)療器械生物學(xué)評價第六部分：植入后局部反應(yīng)試驗,用局部植入法測定實驗金屬的體內(nèi)毒性。將直徑2mm,長6mm的圓柱狀合金樣品植入新西蘭兔股骨,分別于術(shù)后4周、12周、26周處死一組動物,采集標本。 4.用普通X光機拍攝觀察金屬對植入骨骨質(zhì)的影響。 5.制作脫鈣切片和不脫鈣超硬組織切片,觀察合金對周圍骨質(zhì)是否有炎癥、壞死、腫瘤等不良影響。 結(jié)果： 1. TNTZ的溶血率為2.3%,低于國家使用標準(5%)。 2. TNTZ不影響L929細胞的形態(tài),各實驗組細胞形態(tài)及數(shù)量相仿,細胞呈梭形或多角形,有偽足伸出。TNTZ組的MTT值為1.031±0.059, S期比率為40.32±5.49,與對照組比較均無統(tǒng)計學(xué)差異(P0.05),細胞毒性為0級。 3. TNTZ植入兔股骨后未影響創(chuàng)口愈合,未引起炎癥、腫瘤,種植體-骨組織界面緊密貼合,無溶骨現(xiàn)象出現(xiàn),對實驗動物無毒性作用。 結(jié)論： 1. TNTZ基本無溶血作用,無細胞毒性,對實驗動物無不良影響,符合國家使用標準。 2. TNTZ與骨的結(jié)合只是單純的接觸,無骨性結(jié)合,生物應(yīng)用前應(yīng)繼續(xù)研究其表面處理與活化,提高與人體的適應(yīng)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 鹵0.059 and 40.32 鹵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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R318.08

【參考文獻】

相關(guān)期刊論文 前8條

1 李佐臣,李常亮,裘松波,汪大林,郭天文;外科植入TAMZ合金生物學(xué)評價[J];稀有金屬材料與工程;1998年01期

2 呂曉迎;國際標準化組織7406技術(shù)報告牙科材料的生物學(xué)評價[J];口腔材料器械雜志;1995年01期

3 呂榮;王軍;徐新智;吳拮;;塑料包埋非脫鈣骨技術(shù)在骨組織學(xué)與圖像分析中的應(yīng)用[J];臨床與實驗病理學(xué)雜志;2006年03期

4 奚廷斐,楊曉芳;生物材料生物相容性的分子水平評價研究[J];生物醫(yī)學(xué)工程學(xué)雜志;1999年S1期

5 趙永康,武志強,艾紅軍,李述軍,鄭彩云;鈦合金對牙齦成纖維細胞生物學(xué)行為的影響[J];實用口腔醫(yī)學(xué)雜志;2005年05期

6 何寶明;生物醫(yī)用鈦及其合金材料的開發(fā)應(yīng)用進展、市場狀況及問題分析[J];新材料產(chǎn)業(yè);2003年07期

7 呂曉迎;牙科材料細胞毒性評定的新方法（MTT試驗）[J];中華口腔醫(yī)學(xué)雜志;1995年06期

8 李軍;李佐臣;陳杜娟;;新型外科植入用鈦合金TZNT的生物相容性[J];中國有色金屬學(xué)報;2010年04期

，

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