Effects of CoCr metal wear debris generated from metal-on-metal hip implants and Co ions on human monocyte-like U937 cells

• Metal debris in combination with Co ions influence cell function.
• Pre-exposure to Co ions seems to sensitise cells to the toxic effects particles.
• Experimental conditions may not allow to discriminate between cytotoxic and cytostatic.
• Cellular activation state affects the biological response to wear debris.
• Interaction between circulating ions and particles may threaten MoM device surviva.

Hip resurfacing with cobalt–chromium (CoCr) alloy was developed as a surgical alternative to total hip replacement. However, the biological effects of nanoparticles generated by wear at the metal-on-metal articulating surfaces has limited the success of such implants. The aim of this study was to investigate the effects of the combined exposure to CoCr nanoparticles and cobalt ions released from a resurfacing implant on monocytes (U937 cells) and whether these resulted in morphology changes, proliferation alterations, toxicity and cytokine release. The interaction between prior exposure to Co ions and the cellular response to nanoparticulate debris was determined to simulate the situation in patients with metal-on-metal implants receiving a second implant. Effects on U937 cells were mainly seen after 120 h of treatment. Prior exposure to Co ions increased the toxic effects induced by the debris, and by Co ions themselves, suggesting the potential for interaction in vivo. Increased TNF-α secretion by resting cells exposed to nanoparticles could contribute to osteolysis processes in vivo, while increased IFN-γ production by activated cells could represent cellular protection against tissue damage. Data suggest that interactions between Co ions and CoCr nanoparticles would occur in vivo, and could threaten the survival of a CoCr metal implant.