Evaluating the potential hepatotoxicity from hip implant wear products—An in-vitro and in-vivo study

Total hip replacement (THR) is recognized as an effective treatment for patients suffering from severe arthritis or hip issues, with approximately 2.5 million hip and knee replacements recorded annually (AJJR, 2021). A significant clinical concern associated with THR is the toxicity caused by metal particles and ions released from the implant surfaces, which can damage local tissue and potentially spread to distant organs, resulting in systemic toxicity. The toxicity, influenced by the size and concentration of the particles and ions, is especially critical in the liver, the body's main metabolic organ and a primary site for implant accumulation. In this study, we aim to investigate the hepatotoxicity of increasing concentrations of cobalt-chromium-molybdenum (CoCrMo) and titanium (Ti) particles/ions (generally called wear products) in remote organs, particularly the liver. We found that these particles and ions enter cells through metal ion transporters and phagocytosis, leading to significant cellular damage, with titanium ions exhibiting the highest toxicity levels, followed by cobalt ions and CoCrMo particles. Our combined <i>in-vitro</i> and <i>in-vivo</i> research supports the hypothesis that metal particles and ions from implants pose a substantial risk of liver cell damage. This underscores the importance of addressing the systemic impacts of implant-derived metal toxicity in patients with THR.