PMID- 23997019 OWN - NLM STAT- MEDLINE DCOM- 20150512 LR - 20200930 IS - 1552-4981 (Electronic) IS - 1552-4973 (Linking) VI - 102 IP - 1 DP - 2014 Jan TI - In vitro macrophage response to nanometer-size chromium oxide particles. PG - 149-59 LID - 10.1002/jbm.b.32991 [doi] AB - An increasing number of studies have reported adverse tissue reactions around metal-on-metal (MM) hip implants. However, the origin and mechanisms of these reactions remain unclear. Moreover, the biological effects of nanometer-size chromium oxide particles, the predominant type of wear particles produced by MM implants, remain mostly unknown. The purpose of this study was to analyze the cytotoxic effects of clinically relevant nanometer-size chromium oxide particles on macrophage response in vitro. J774.A1 macrophages were cultured with either 60 nm or 700 nm commercially available Cr2 O3 particles at different concentrations. Two different particle sizes were analyzed to evaluate potential volume effects. Cell mortality was analyzed by light microscopy, flow cytometry (annexin V-fluorescein isothiocyanate and propidium iodide assay), and using a cell death detection enzyme-linked immunosorbant assay (ELISA). Tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 alpha (MIP-1alpha) release was measured by ELISA, and gene expression was analyzed by quantitative real-time PCR. Results showed that, at high concentrations, Cr2 O3 particles of both sizes can be cytotoxic, inducing significant decreases in total cell numbers and increases in necrosis. Results also suggested that these effects were dependent on particle volume. However, TNF-alpha, MCP-1, and MIP-1alpha cytokine release and gene expression remained low. Overall, this study demonstrates that nanometer-size particles of Cr2 O3 , a stable form of chromium oxide ceramic, have rather low cytotoxic effects on macrophages. Therefore, these particles may not be the main culprit in the initiation of the inflammatory reaction in MM periprosthetic tissues. However, other parameters (e.g., potential intracellular damage) remain to be investigated. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - VanOs, Robilyn AU - VanOs R AD - Department of Mechanical Engineering, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. FAU - Lildhar, Levannia L AU - Lildhar LL FAU - Lehoux, Eric A AU - Lehoux EA FAU - Beaule, Paul E AU - Beaule PE FAU - Catelas, Isabelle AU - Catelas I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130829 PL - United States TA - J Biomed Mater Res B Appl Biomater JT - Journal of biomedical materials research. Part B, Applied biomaterials JID - 101234238 RN - 0 (Biocompatible Materials) RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccl3 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Chromium Compounds) RN - 0 (Tumor Necrosis Factor-alpha) RN - X5Z09SU859 (chromic oxide) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Biocompatible Materials/chemistry/*toxicity MH - Cell Line MH - Chemokine CCL2/genetics/metabolism MH - Chemokine CCL3/genetics/metabolism MH - Chromium Compounds/chemistry/*toxicity MH - Equipment Failure Analysis MH - Gene Expression/drug effects MH - Hip Prosthesis/adverse effects MH - Humans MH - Macrophage Activation/*drug effects/physiology MH - Macrophages/drug effects/pathology/physiology MH - Materials Testing MH - Metal Nanoparticles/chemistry/*toxicity/ultrastructure MH - Mice MH - Necrosis MH - Particle Size MH - Prosthesis Failure MH - Tumor Necrosis Factor-alpha/genetics/metabolism OTO - NOTNLM OT - chromium oxide OT - cytotoxicity OT - hip implants OT - macrophages OT - wear particles EDAT- 2013/09/03 06:00 MHDA- 2015/05/13 06:00 CRDT- 2013/09/03 06:00 PHST- 2012/10/22 00:00 [received] PHST- 2013/04/05 00:00 [revised] PHST- 2013/05/28 00:00 [accepted] PHST- 2013/09/03 06:00 [entrez] PHST- 2013/09/03 06:00 [pubmed] PHST- 2015/05/13 06:00 [medline] AID - 10.1002/jbm.b.32991 [doi] PST - ppublish SO - J Biomed Mater Res B Appl Biomater. 2014 Jan;102(1):149-59. doi: 10.1002/jbm.b.32991. Epub 2013 Aug 29.