In vitro analysis of the cytotoxic and anti-inflammatory effects of antioxidant compounds used as additives in ultra high-molecular weight polyethylene in total joint replacement components.
In vitro analysis of the cytotoxic and anti-inflammatory effects of antioxidant compounds used as additives in ultra high-molecular weight polyethylene in total joint replacement components.
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DOI：
10.1002/jbm.b.32798
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发表时间：
2013-04
影响因子：
3.4
通讯作者：
Tipper, J. L.
中科院分区：
文献类型：
--
作者：
Bladen, C. L.;Tzu-Yin, L.;Fisher, J.;Tipper, J. L.
超高相对分子质量聚乙烯(UHMWPE)仍然是现代关节置换假体中最常用的材料。然而，UHMWPE磨损颗粒作为轴承关节形成，是导致关节置换失败的主要因素之一，它通过诱导骨溶解和随后的无菌性松动而导致。此前的研究表明，在UHMWPE中添加维生素E等抗氧化剂可以提高聚合物的耐磨性，减少氧化疲劳。然而，人们对这种抗氧化剂化学物质的生物学后果知之甚少。这项研究调查了目前正在实验中用于髋关节和膝关节假体的各种抗氧化剂化合物，包括氮氧化物、受阻酚和稀土元素对体外培养的U937人组织细胞和人外周血单核细胞(PBMNCs)的细胞毒性和抗炎作用。加入这些化合物后，通过剂量反应细胞毒性研究确定细胞活性。通过测定脂多糖刺激的细胞释放肿瘤坏死因子α的量来确定其抗炎作用。研究表明，许多化合物在相对较低的浓度(微摩尔)下对U937细胞和PBMNC具有细胞毒性，特别是受阻的苯酚3，5-二叔丁基-4-羟基肉桂酸酯(HPAO1)和氮氧化物2，2，6，6-四甲基哌啶1-氧(TEMPO)。镧系元素只有在很高的浓度下才具有细胞毒性，而在较低的浓度下对细胞的耐受性很好。细胞毒性化合物的抗炎作用也有所减弱，特别是在PBMNC中。因此，应认真考虑将这些化合物中的任何一种用作超高相对分子质量聚乙烯的潜在添加剂。2012 Wiley期刊，Inc.生物材料资源B部分：应用生物材料，101B：407-413,2013。
Ultra high-molecular weight polyethylene (UHMWPE) remains the most commonly used material in modern joint replacement prostheses. However, UHMWPE wear particles, formed as the bearing articulates, are one of the main factors leading to joint replacement failure via the induction of osteolysis and subsequent aseptic loosening. Previous studies have shown that the addition of antioxidants such as vitamin E to UHMWPE can improve wear resistance of the polymer and reduce oxidative fatigue. However, little is known regarding the biological consequences of such antioxidant chemicals. This study investigated the cytotoxic and anti-inflammatory effects of a variety of antioxidant compounds currently being tested experimentally for use in hip and knee prostheses, including nitroxides, hindered phenols, and lanthanides on U937 human histocyte cells and human peripheral blood mononuclear cells (PBMNCs) in vitro. After addition of the compounds, cell viability was determined by dose response cytotoxicity studies. Anti-inflammatory effects were determined by quantitation of TNF-α release in lipopolysaccharide (LPS)-stimulated cells. This study has shown that many of these compounds were cytotoxic to U937 cells and PBMNCs, at relatively low concentrations (micromolar), specifically the hindered phenol 3,5-di-tert-butyl-4-hydroxyhydrocinnamate (HPAO1), and the nitroxide 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO). Lanthanides were only cytotoxic at very high concentrations and were well tolerated by the cells at lower concentrations. Cytotoxic compounds also showed reduced anti-inflammatory effects, particularly in PBMNCs. Careful consideration should therefore be given to the use of any of these compounds as potential additives to UHMWPE. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 407–413, 2013.
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