John Fisher is an NIHR senior investigator.
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†
Article first published online: 22 AUG 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Biomedical Materials Research Part B: Applied Biomaterials
Volume 101B, Issue 3, pages 407–413, April 2013
How to Cite
Bladen, C. L., Tzu-Yin, L., Fisher, J. and Tipper, J. L. (2013), 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. J. Biomed. Mater. Res., 101B: 407–413. doi: 10.1002/jbm.b.32798
How to cite this article: Bladen CL, Tzu-Yin L, Fisher J, Tipper JL. 2013. 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. J Biomed Mater Res Part B 2013:101B:407–413.
- Issue published online: 18 MAR 2013
- Article first published online: 22 AUG 2012
- Manuscript Accepted: 28 JUN 2012
- Manuscript Revised: 26 JUN 2012
- Manuscript Received: 12 JAN 2012
- WELMEC, a Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC. Grant Number: WT 088908/Z/09/Z
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.