人工关节用超低磨损聚乙烯生物相容性、摩擦学性能与磨屑表征研究

发布时间：2018-04-22 15:26

本文选题：生物相容性 + 人工关节　；参考：《北京协和医学院》2014年博士论文

【摘要】：研究背景及目的人工关节置换术是治疗中晚期严重髋、膝骨关节病的主要手段,可以有效缓解关节疼痛、改善畸形和重建关节功能,但其使用寿命往往受到假体松动的制约。人工关节摩擦磨损产生的磨屑尤其是聚乙烯磨屑,极易引起生物学反应,继发假体周围骨溶解并最终导致假体无菌性松动,成为限制假体使用寿命的最主要因素。如何提高假体材料尤其是聚乙烯部件的耐磨损性能成为人工关节材料研究的热点。超高分子量聚乙烯(ultra-high-molecular weight polyethylene, UHMWPE)因其优异的生物相容性、机械性能以及耐磨损性能,是目前人工关节主要的摩擦界面材料。通过辐射交联和添加维生素E等方式,UHMWPE耐磨损性能进一步得到改良。人工关节植入级UHMWPE的制备工艺复杂,多依赖进口,成本昂贵,过度交联往往导致其机械强度降低而脆性增加,且不能直接注塑成型。寻找更好的人工关节聚乙烯替代材料并国产化,成为当前迫切需要解决的问题。超低磨损聚乙烯(ultra-low-wear polyethylene, ULWPE)是国内聚烯烃专家自主研发的一种新型高分子聚乙烯材料,易于加工并可直接注塑,前期试验证明其耐磨损性优于UHMWPE。本课题目的在于进一步研究ULWPE材料的生物相容性和生物摩擦学性能,提取磨屑并进行初步的表征分析,为将来可能的临床应用提供科学的实验依据。方法 1.按照国家GB/T-16886/ISO-10993医疗器械生物学评价的标准,对ULWPE进行体外细胞毒性试验(CCK-8比色法)、血液相容性试验(溶血试验)、急性全身毒性试验、肌肉植入试验和慢性全身毒性(肝肾功能毒性)试验。 2.模拟体内润滑(50%小牛血清)条件下,在BiotriboPOD Type Zero型摩擦磨损试验机上分别对人工关节超低磨损聚乙烯、传统超高分子量聚乙烯(conventional UHMWPE, CPE)和高交联超高分子量聚乙烯(highly cross-linked UHMWPE, HXLPE)销试样与摩擦配副钴铬钼圆盘进行为期200万周次的销-盘摩擦磨损试验,观察销试样表面磨损形貌,测量并计算磨损量、磨损率和磨损因数。 3.通过盐酸消化+真空冷冻干燥技术提取ULWPE磨屑,利用扫描电镜(SEM)对磨屑进行初步的形貌、粒径等表征分析。结果 1.生物相容性试验结果 1)细胞毒性试验：试验组L929细胞在培养24h、48h、72h后相对增殖率依次为95.25%、104.96%、102.81%,显示无细胞毒性； 2)血液相容性试验：溶血率为0.81%,提示该材料无溶血作用； 3)急性全身毒性试验：试验组小鼠无特殊行为学表现,试验组与对照组小鼠体重增加t检验差异无统计学意义(P0.05)； 4)肌肉植入试验：术后病理切片证实该材料植入大鼠体内后炎症反应逐渐减轻,材料周围有完整致密纤维结缔组织包裹； 5)慢性全身毒性试验：术后12周试验动物肝、肾均无明显病理表现。 2. ULWPE、HXLPE、CPE销试样磨损率分别为0.428mm3/百万次、0.915mmm3/百万次和1.912mm3/百万次,摩损因数分别为1.945×10-6mm3/N·m、4.16X10-6mm3/N·m和8.62×10-6mm3/·m,ULWPE的磨损率和摩损因数最低。 3.ULWPE磨损表面形貌以较浅的犁沟和表面划痕为主。 4.盐酸消化+真空冷冻干燥技术可以提取分离干燥的ULWPE磨屑。 5.ULWPE磨屑有粒状、片状、块状、纤维状和杆状等多种形态,其中粒状磨屑最多,片状磨屑次之。粒径尺寸各不相同,大到200μm以上,小到1μm以下。结论 1. ULWPE无细胞毒性、无急性溶血、无急慢性全身毒性,材料植入后对机体组织刺激小,具有良好的生物相容性及安全性,符合医用生物植入材料的基本要求。 2. ULWPE磨损表面形貌和磨损率显示其磨损最轻微,耐磨损性能明显优于HXLPE及CPE,从生物摩擦学角度上具备替代现有UHMWPE的可能性。 3.盐酸消化+真空冷冻干燥技术可以提取分离干燥的ULWPE磨屑而不破坏其表面形貌及粒径,方法有效可行且无污染。 4.ULWPE磨屑的存在形态有粒状、片状、块状、纤维状和杆状等,形态各异,其中粒状磨屑数目最多,片状磨屑次之；粒径尺寸也各不相同,分布范围广。 5. ULWPE磨损表面形貌与磨屑表征分析均表明其存在粘着磨损、磨粒磨损和疲劳磨损三种磨损机理。
[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 .

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318.17

【参考文献】