本文選題：生物相容性 + 人工關(guān)節(jié)　； 參考：《北京協(xié)和醫(yī)學院》2014年博士論文

【摘要】：研究背景及目的 人工關(guān)節(jié)置換術(shù)是治療中晚期嚴重髖、膝骨關(guān)節(jié)病的主要手段,可以有效緩解關(guān)節(jié)疼痛、改善畸形和重建關(guān)節(jié)功能,但其使用壽命往往受到假體松動的制約。人工關(guān)節(jié)摩擦磨損產(chǎn)生的磨屑尤其是聚乙烯磨屑,極易引起生物學反應,繼發(fā)假體周圍骨溶解并最終導致假體無菌性松動,成為限制假體使用壽命的最主要因素。如何提高假體材料尤其是聚乙烯部件的耐磨損性能成為人工關(guān)節(jié)材料研究的熱點。 超高分子量聚乙烯(ultra-high-molecular weight polyethylene, UHMWPE)因其優(yōu)異的生物相容性、機械性能以及耐磨損性能,是目前人工關(guān)節(jié)主要的摩擦界面材料。通過輻射交聯(lián)和添加維生素E等方式,UHMWPE耐磨損性能進一步得到改良。人工關(guān)節(jié)植入級UHMWPE的制備工藝復雜,多依賴進口,成本昂貴,過度交聯(lián)往往導致其機械強度降低而脆性增加,且不能直接注塑成型。尋找更好的人工關(guān)節(jié)聚乙烯替代材料并國產(chǎn)化,成為當前迫切需要解決的問題。 超低磨損聚乙烯(ultra-low-wear polyethylene, ULWPE)是國內(nèi)聚烯烴專家自主研發(fā)的一種新型高分子聚乙烯材料,易于加工并可直接注塑,前期試驗證明其耐磨損性優(yōu)于UHMWPE。本課題目的在于進一步研究ULWPE材料的生物相容性和生物摩擦學性能,提取磨屑并進行初步的表征分析,為將來可能的臨床應用提供科學的實驗依據(jù)。 方法 1.按照國家GB/T-16886/ISO-10993醫(yī)療器械生物學評價的標準,對ULWPE進行體外細胞毒性試驗(CCK-8比色法)、血液相容性試驗(溶血試驗)、急性全身毒性試驗、肌肉植入試驗和慢性全身毒性(肝腎功能毒性)試驗。 2.模擬體內(nèi)潤滑(50%小牛血清)條件下,在BiotriboPOD Type Zero型摩擦磨損試驗機上分別對人工關(guān)節(jié)超低磨損聚乙烯、傳統(tǒng)超高分子量聚乙烯(conventional UHMWPE, CPE)和高交聯(lián)超高分子量聚乙烯(highly cross-linked UHMWPE, HXLPE)銷試樣與摩擦配副鈷鉻鉬圓盤進行為期200萬周次的銷-盤摩擦磨損試驗,觀察銷試樣表面磨損形貌,測量并計算磨損量、磨損率和磨損因數(shù)。 3.通過鹽酸消化+真空冷凍干燥技術(shù)提取ULWPE磨屑,利用掃描電鏡(SEM)對磨屑進行初步的形貌、粒徑等表征分析。 結(jié)果 1.生物相容性試驗結(jié)果 1)細胞毒性試驗：試驗組L929細胞在培養(yǎng)24h、48h、72h后相對增殖率依次為95.25%、104.96%、102.81%,顯示無細胞毒性； 2)血液相容性試驗：溶血率為0.81%,提示該材料無溶血作用； 3)急性全身毒性試驗：試驗組小鼠無特殊行為學表現(xiàn),試驗組與對照組小鼠體重增加t檢驗差異無統(tǒng)計學意義(P0.05)； 4)肌肉植入試驗：術(shù)后病理切片證實該材料植入大鼠體內(nèi)后炎癥反應逐漸減輕,材料周圍有完整致密纖維結(jié)締組織包裹； 5)慢性全身毒性試驗：術(shù)后12周試驗動物肝、腎均無明顯病理表現(xiàn)。 2. ULWPE、HXLPE、CPE銷試樣磨損率分別為0.428mm3/百萬次、0.915mmm3/百萬次和1.912mm3/百萬次,摩損因數(shù)分別為1.945×10-6mm3/N·m、4.16X10-6mm3/N·m和8.62×10-6mm3/·m,ULWPE的磨損率和摩損因數(shù)最低。 3.ULWPE磨損表面形貌以較淺的犁溝和表面劃痕為主。 4.鹽酸消化+真空冷凍干燥技術(shù)可以提取分離干燥的ULWPE磨屑。 5.ULWPE磨屑有粒狀、片狀、塊狀、纖維狀和桿狀等多種形態(tài),其中粒狀磨屑最多,片狀磨屑次之。粒徑尺寸各不相同,大到200μm以上,小到1μm以下。 結(jié)論 1. ULWPE無細胞毒性、無急性溶血、無急慢性全身毒性,材料植入后對機體組織刺激小,具有良好的生物相容性及安全性,符合醫(yī)用生物植入材料的基本要求。 2. ULWPE磨損表面形貌和磨損率顯示其磨損最輕微,耐磨損性能明顯優(yōu)于HXLPE及CPE,從生物摩擦學角度上具備替代現(xiàn)有UHMWPE的可能性。 3.鹽酸消化+真空冷凍干燥技術(shù)可以提取分離干燥的ULWPE磨屑而不破壞其表面形貌及粒徑,方法有效可行且無污染。 4.ULWPE磨屑的存在形態(tài)有粒狀、片狀、塊狀、纖維狀和桿狀等,形態(tài)各異,其中粒狀磨屑數(shù)目最多,片狀磨屑次之；粒徑尺寸也各不相同,分布范圍廣。 5. ULWPE磨損表面形貌與磨屑表征分析均表明其存在粘著磨損、磨粒磨損和疲勞磨損三種磨損機理。
[Abstract]:Background and purpose of study

Artificial joint replacement is the main method of treatment of severe hip and knee joint disease in the middle and late stage . It can effectively relieve the joint pain , improve the deformity and reconstruct the joint function , but the service life is often restricted by the loosening of the prosthesis .

The ultra - high molecular weight polyethylene ( UHMWPE ) is the main friction interface material at present because of its excellent biocompatibility , mechanical properties and wear resistance .

Ultra - low - wear polyethylene ( ULWPE ) is a new type of high molecular polyethylene material developed by domestic polyolefin experts , which is easy to be processed and can be injection molded directly . The purpose of this research is to study the biocompatibility and tribological properties of ULWPE material . The purpose of this research is to further study the biocompatibility and tribological properties of ULWPE materials , to extract the grinding chips and to carry out preliminary characterization and analysis , and to provide scientific experimental basis for possible clinical applications in the future .

method

1 . Carry out in vitro cytotoxicity test ( CCK - 8 colorimetry ) , blood compatibility test ( hemolysis test ) , acute systemic toxicity test , muscle implantation test and chronic systemic toxicity ( hepatorenal function toxicity ) test on ULWPE according to the national standard of GB / T - 16886 / ISO - 10993 Biological Evaluation of Medical Devices .

2 . Under the condition of simulating in vivo lubrication ( 50 % calf serum ) , a two - million - week pin - disc friction and wear test on ultra - low - wear polyethylene , conventional UHMWPE , CPE and highly cross - linked UHMWPE ( HXLPE ) pin and high cross - linked UHMWPE ( highly cross - linked UHMWPE , HXLPE ) pin and high cross - linked UHMWPE ( highly cross - linked UHMWPE , HXLPE ) pin and high cross - linked UHMWPE ( highly cross - linked UHMWPE , HXLPE ) pin and high cross - linked UHMWPE ( highly cross - linked UHMWPE , HXLPE ) pin were investigated . The wear pattern , wear rate and wear factor were measured and calculated .

3 . ULWPE mill was extracted by hydrochloric acid digestion + vacuum freeze - drying technology . The morphology and particle size were analyzed by scanning electron microscope ( SEM ) .

Results

1 . Biocompatibility Test Results

1 ) Cytotoxicity test : L929 cells in the test group were 95 . 25 % , 104 . 96 % and 102 . 81 % after 24 h , 48 h and 72 h culture , showing no cytotoxicity ;


2 ) Blood compatibility test : Hemolysis rate was 0.81 % , indicating that the material had no hemolytic effect ;


3 ) Acute systemic toxicity test : there was no special behavior in the test group mice , and there was no significant difference between the test group and the control group ( P0.05 ) .


4 ) muscle implantation test : the post - operative pathological section confirmed that the inflammatory reaction gradually alleviated after the material was implanted in rats , and the surrounding of the material was wrapped with intact dense fibrous connective tissue ;


5 ) Chronic systemic toxicity test : There was no obvious pathological manifestation of liver and kidney in 12 weeks after operation .

2 . The wear rates of ULWPE , HXLPE and CPE pin samples were 0.428 mm3 / million , 0.915 mmm3 / million and 1.912mm3 / million respectively , and the wear factors were 1.945 脳 10 - 6mm3 / N 路 m , 4.16X10 - 6mm3 / N 路 m and 8.62 脳 10 - 6mm3 / 路 m , and the wear rate and friction factor of ULWPE were the lowest .

3 . The surface topography of ULWPE is dominated by shallow furrow and surface scratch .

4 . hydrochloric acid digestion + vacuum freeze - drying technology can extract and separate dry ULWPE grinding chips .

5 . ULWPE grinding chips are in granular , sheet - like , block - like , fibrous and rod - like shapes , in which the size of the granular grinding chips is the most , and the size of the sheet - shaped grinding chips is different , and the particle size is larger to 200 . m u.m or less and smaller than 1.mu . m .

Conclusion

1 . ULWPE has no cytotoxicity , no acute hemolysis , no acute and chronic systemic toxicity , small irritation to organism tissue after material implantation , good biocompatibility and safety , and conforms to the basic requirements of medical biological implant materials .

2 . The wear surface morphology and wear rate of ULWPE show that the wear is minimal , the wear resistance is obviously superior to HXLPE and CPE , and the possibility of replacing the existing UHMWPE from the viewpoint of tribology .

3 . The technology of hydrochloric acid digestion + vacuum freeze - drying can extract and separate dried ULWPE grinding chips without destroying its surface morphology and particle size , and the method is effective and feasible and is free of pollution .

4 . The existence form of ULWPE grinding chips is granular , flake , block , fibrous and rod - like , and the form is different , in which the number of granular grinding chips is the most , and the chip - like grinding chip is the second ;
and the size of the particles is different and the distribution range is wide .

5 . The wear surface morphology of ULWPE and the analysis of wear debris indicate that there are three wear mechanisms of adhesive wear , abrasive wear and fatigue wear .

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R318.17

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