Toxicity and oxidative stress of nano- and micro-CoCrMo particles
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1
School of Medicine, West Virginia University, Orthopaedics, United States
Metal-on-metal (MoM) joint implants are used routinely during total hip and knee replacements and are typically composed of cobalt chromium molybdenum (CoCrMo) alloys. CoCrMo “wear particles”, in the nano- and micro-size ranges, are generated in situ. Meanwhile, occupational exposure to CoCrMo particles may be associated with the development of industrial dental worker’s pneumoconiosis and pulmonary exposure to CoCrMo particles is therefore a relevant concern in the manufacturing of MoM implants. The objective of this study was to examine the toxicity of nano- and micro-CoCrMo particles and to determine whether their exposure induced oxidative stress in human lung epithelial cells, osteoblasts and macrophages. Micro-CoCrMo particles were atomized powders and were further used to produce nano-CoCrMo particles via mechanical milling. Lung epithelial cells, osteoblasts, and macrophages were exposed to nano- and micro-CoCrMo particles and evaluated for cell viability and oxidative stress. Statistical analysis was conducted and P < 0.05 was considered significant.
We found that both nano- and micro-CoCrMo particles can induce toxicity to osteoblasts and lung epithelial cells at doses of 100 µg/mL or higher and to macrophages at doses of 10 µg/mL or higher (Fig. 1), and the toxicity and oxidative responses are cell specific (Table 1). Compared to micro-CoCrMo particles, nano-CoCrMo particles resulted in significantly lower viability of macrophages at 1000 µg/mL and significantly higher viability of lung epithelial cells at 100 and 1000 µg/mL and osteoblasts at 1000 µg/mL. At the same dose, significantly reduced viability of macrophages was also seen at shorter exposure times exposed to nano-CoCrMo compared to micro-CoCrMo. Meanwhile, compared to control, both nano- and micro-CoCrMo may lead to significantly increased 2’,7’-dichlorofluorescein diacetate (DCF) levels in the cell types tested. Compared to control, no significant differences in dihydroethidium (DHE) levels were observed in lung epithelial cells while significantly higher DHE levels were found in both osteoblasts and macrophages. Compared to micro-CoCrMo, nano-CoCrMo particle treatment also caused significantly higher DCF levels in all three types of cells at high particle concentrations (i.e. 100 and 1000 µg/mL) and significantly lower DCF levels at 0.1, 1 and 10 µg/mL in macrophages. Nano-CoCrMo, compared to micro-CoCrMo, also resulted in significantly lower DHE levels at 0.1, 1, 10 and 100 µg/mL and significantly higher DHE levels at 1000 µg/mL in osteoblasts. Our findings highlight the potential roles that nano- and micro-CoCrMo particles, whether exposure is due to inhalation or implant wear, and associated oxidative stress may play in the increasingly reported implant loosening, osteolysis and systemic complications in orthopaedic patients, and may explain the risk of lung diseases in dental workers.
We acknowledge financial support from the AO Foundation (Project S-13-15 L was supported by the AO Foundation) and the West Virginia National Aeronautics and Space Administration Experimental Program to Stimulate Competitive Research (WV NASA EPSCoR). AA thanks the American Foundation for Pharmaceutical Education for her Pre-Doctoral Fellowship in Pharmaceutical Sciences award 2012-14. We acknowledge use of the WVU Shared Research Facilities.
Keywords:
biomaterial,
Biocompatibility,
Cell response,
Nano/micro particle
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Safety and toxicity evaluation for biomaterials
Citation:
Armstead
A and
Li
B
(2016). Toxicity and oxidative stress of nano- and micro-CoCrMo particles.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.02143
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.