As the population ages there is a greater incidence of age-related musculoskeletal diseases such as osteoarthritis. This means that there is an increasing need for effective and long-lasting joint replacements. Metal-on-metal hip replacements have been used as an alternative to conventional ceramic or plastic implants but some patients have suffered adverse inflammatory reactions, including pain and the development of benign growths known as pseudotumours. The mechanisms behind this inflammation are unknown. This project aims to investigate this process.
Recent work has shown that cobalt from metal-on-metal joints can activate an immune cell surface receptor called toll-like receptor 4 (TLR4), leading to inflammation. This research will investigate the inflammatory effects of orthopaedic metals, including cobalt, chromium and molybdenum, with a particular focus on the TLR4 signalling pathway. One of the main aims of the project is to develop an assay that will allow the testing of orthopaedic materials to determine whether or not they activate the human immune system.
There is considerable variability in the patient response to metal ions but the reasons for this remain unknown. The project will investigate genetic factors that may influence patient susceptibility to orthopaedic metals. The outcomes of this work will provide insights into inflammatory mechanisms underlying metal-on-metal joint replacements failure and may lead to the identification of potential therapeutic opportunities to prevent inflammation.