The effect of particulate biomaterials and motion on aseptic loosening of orthopaedic implants

The pathogenesis of aseptic loosening of orthopaedic total joint prostheses is not clearly understood. Two features are associated with the loosened implant/host bone interface: particulate debris and implant motion. While numerous studies have evaluated the cellular response to particulate biomaterials, few studies have investigated the influence of implant motion on the biological response. The principal aim of this study was to test the hypothesis that "excessive mechanical stimulation to the periprosthetic tissues induces an inflammatory response and the addition of particulate biomaterials intensifies this response." Three approaches were taken: immunohistochemical analysis of interface tissues from clinical cases, an in vitro model, and in vivo model.; The inflammatory response of tissues surrounding loosened total joint implants was characterized by the presence of macrophages, fibroblasts, and T-lymphocytes and the cytokines IL-1{dollar}beta{dollar}, IL-6, and TNF-{dollar}alpha{dollar}. Our in vitro experiments demonstrated that particulate polymethylmethacrylate (4.0, 40.0 gm/well) and cyclic loading (0.5 Hz., 0.2 strain) decreased DNA synthesis in P388D1 macrophages but not in human synovial fibroblasts. These test conditions did not alter cytokine expression (IL-1{dollar}beta{dollar}, IL-6, TNF-{dollar}alpha{dollar}) by either cell type. Our in vivo experiments indicate that repetitive movement of an implant (with or without particulate polymethylmethacrylate) results in: (1) the development of an interface membrane containing large numbers of histiocytes and staining positively for IL-1{dollar}beta{dollar}, IL-6, and TNF-{dollar}alpha{dollar} and (2) evidence of osteoblastic and osteoclastic activity. Addition of particulate polymethylmethacrylate (PMMA) around a moving implant increased the staining intensity and distribution for the inflammatory cytokines as well as increased bone resorption. The response to the stable implants was benign with no evidence of osteolysis. IL-1{dollar}beta{dollar}, IL-6, and TNF-{dollar}alpha{dollar} were detected in the tissues around stable implants with or without particulate PMMA by 6 months.; Our results indicate that mechanical stimulation of the cells found within the implant interface tissues induces an inflammatory response and that particulate PMMA exacerbates this response. The mechanism of action appears to be through a recruitment and/or stimulation of proliferation of macrophages and the elaboration of mediators (IL-1{dollar}beta{dollar}, IL-6, and TNF-{dollar}alpha{dollar}) known to be associated with inflammation.