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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\u2010inflammatory 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) <jats:italic>in vitro<\/jats:italic>. After addition of the compounds, cell viability was determined by dose response cytotoxicity studies. Anti\u2010inflammatory effects were determined by quantitation of TNF\u2010\u03b1 release in lipopolysaccharide (LPS)\u2010stimulated 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\u2010di\u2010tert\u2010butyl\u20104\u2010hydroxyhydrocinnamate (HPAO1), and the nitroxide 2,2,6,6\u2010Tetramethylpiperidine 1\u2010oxyl (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\u2010inflammatory effects, particularly in PBMNCs. Careful consideration should therefore be given to the use of any of these compounds as potential additives to UHMWPE. \u00a9 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 407\u2013413, 2013.<\/jats:p>","DOI":"10.1002\/jbm.b.32798","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T13:19:17Z","timestamp":1345641557000},"page":"407-413","source":"Crossref","is-referenced-by-count":18,"title":["<i>In vitro<\/i> analysis of the cytotoxic and anti\u2010inflammatory effects of antioxidant compounds used as additives in ultra high\u2010molecular weight polyethylene in total joint replacement components"],"prefix":"10.1002","volume":"101B","author":[{"given":"C. L.","family":"Bladen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Tzu\u2010Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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