Repeated Low Dose Injection of Cobalt Chromium Microparticles in a Mouse Knee Model Induces Robust Inflammation with Cartilage and Bone Loss (INC1P.345)

Abstract Total joint arthroplasty is a well accepted orthopaedic procedure for the treatment of many pathological joint conditions, but the release of metallic wear debris such as cobalt chromium (CoCr) microparticles can lead to pain, osteolysis, and implant failure. Our studies of periprosthetic tissue samples from patients undergoing revision surgery have shown that these particles induce an M2 macrophage phenotype as evidenced through gene expression analysis and CD68 immunostaining. We used an intra-articular murine knee model to further examine the synovial tissue response to CoCr and have shown that a single high dose (10mg) inoculation of CoCr microparticles triggers a robust type 2 immune response characterized by the presence of alternatively activated macrophages, neutrophils, and eosinophils 2 days after injection. We further examined the long term effects of repeated alternate day low dose (0.5mg) injection of CoCr microparticles on synovial tissues over 14 days. Tissues exposed to CoCr microparticles were found to have increased clinical scores for inflammation with loss of cartilage and bone tissue at day 14 when compared to controls. Together these studies indicate that exposure of synovial tissues to CoCr induces an innate type 2 immune response with long term hard tissue damage. These studies may ultimately lead to the identification of targeted therapeutic options to locally treat implant associated pain and potentially increase implant longevity.