Murine Model of Progressive Orthopaedic Wear Particle Induced Chronic Inflammation and Osteolysis. Tissue engineering. Part C, Methods Pajarinen, J., Nabeshima, A., Lin, T. H., Sato, T., Gibon, E., Jämsen, E., Lu, L., Nathan, K., Yao, Z., Goodman, S. B. 2017

Abstract

Periprosthetic osteolysis and subsequent aseptic loosening of total joint replacements are driven by byproducts of wear released from the implant. Wear particles cause macrophage mediated inflammation that culminates with periprosthetic bone loss. Most current animal models of particle- induced osteolysis are based on the acute inflammatory reaction induced by wear debris, which is distinct from the slowly progressive clinical scenario. To address this limitation we previously developed a murine model of periprosthetic osteolysis that is based on slow continuous delivery of wear particles into the murine distal femur over a period of 4 weeks. The particle delivery was accomplished by using subcutaneously implanted osmotic pumps and tubing, and a hollow titanium rod press-fit into the distal femur. In this study we report a modification of our prior model in which particle delivery is extended to 8 weeks to better mimic the progressive development of periprosthetic osteolysis and to allow the assessment of interventions in a setting where the chronic particle induced osteolysis is already present at the initiation of the treatment. Compared to 4 week samples extending the particle delivery to 8 weeks significantly exacerbated the local bone loss observed with µCT and the amount of both peri-implant F4/80+ macrophages and TRAP+ osteoclasts detected with immunohistochemical and histochemical stainings. Furthermore systemic recruitment of reporter macrophages to peri-implant tissues observed with bioluminescence imaging continued even at the later stages of particle induced inflammation. This modified model system could provide new insights into the mechanisms of chronic inflammatory bone loss and be particularly useful in assessing the efficacy of treatments in a setting that resembles the clinical scenario of developing periprosthetic osteolysis more closely than currently existing model systems.

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