Radiation impacts on toxicity of cobalt–chromium (CoCr) implant debris

Abstract

Particulate and soluble debris are generated by mechanical and non-mechanical degradation of implanted medical devices. Debris containing cobalt and chromium (CoCr) is known to cause adverse biological reactions. Implant-related complications are often diagnosed using radiography, which results in more frequent patient exposure to ionizing radiation. The aim of this study was to evaluate the potential for increased toxicity due to combined radiation and CoCr exposure. This was investigated using a controlled in vitro model consisting of commercially available CoCr debris that was generated from components of hip replacements and human cell lines relevant to the joint environment: endothelial HMEC-1 and synovial SW982. Particle sizes and shapes were heterogenous. Cells tended to internalize smaller particles, as observed by electron microscopy. Indicators of toxicity were measured after short (24 h after radiation) or extended (12–14 d after radiation) exposure timelines. In the short-term, CoCr reduced cell viability, increased apoptosis, and increased oxidative stress. The effects of radiation were not apparent until the timeline was extended. CoCr and radiation reduced cell survival, with both additive and synergistic effects. Mechanisms for reduced survival included rapid cell death caused by CoCr and senescence caused by radiation. In conclusion, results showed combined toxicological effects of CoCr and radiation at the doses and timelines used for this in vitro model. These observations warrant further investigation using other experimental models to determine translational impact.

Keywords:

• Radiation
• medical device
• implant
• cobalt chromium
• wear debris

Author contributions

Kevin Trout: methodology, investigation, formal analysis, software, visualization, writing – original draft. Sanghamitra Majumdar: ICP-MS study. Anil Patri: scientific guidance for material characterization. Tariq Fahmi: conceptualization, methodology, supervision, project administration. All: writing – review & editing. All authors have read and agreed to the final version of the manuscript.

Disclaimer

This article reflects the views of the authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgments

Angel Paredes, PhD for technical support with electron microscopy. Thanks to members of the Nanotechnology Core Facility for helpful discussions. We are grateful for shared access to equipment from the Division of Genetic and Molecular Toxicology and other NCTR divisions.

Additional information

Funding

This work was supported in part by the Collaborative Opportunities for Research Excellence in Science (CORES) grants program [Protocol number: E0769601] and an appointment to the Research Participation Program at National Center for Toxicological Research (NCTR) of U.S. Food and Drug Administration (FDA), administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between U.S. Department of Energy and FDA.