Development of bioactive bone grafting for periprosthetic osteolysis

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Osteolysis is a challenging problem that occurs after joint arthroplasty. The aim of this study was to analyze the mechanisms of osteolysis and to develop the effective treatment of this condition. In 2002, we showed that polyethylene and titanium particles induced more osteolysis than alumina and zirconia particles using murine calvarial osteolysis model. We also revealed that inflammatory cytokines, TNF-α, IL-1β, IL-6, are involved in this condition. In the experiment on endochondral bone formation, we showed that b-FGF, a cytokine that can increase proliferation of osteoblasts, suppresses endochondral ossification in vivo. In 2003, we have assessed the extent of osteolysis induced by polyethylene, titanium and cobalt-chromium particles and the expression of TNF-α, IL-1β, RANKL, OPG in time course. In this experiment, we found that there are two different mechanisms in particle-induced osteoclastogenesis. In parallel with the analysis of particle-induced osteolysis, we have performed animal studies to develop bioactive bone grafting for the treatment of osteolysis. Autogenic bone marrow cells or bone marrow cell-derived osteoblasts were implanted into bone defects in rats with allogenic bone grafts that carry scaffold and cytokines. Two types of allografts were used in this experiment ; structural or morsellized allografts. Radiological and histological assessments revealed that either implantation of autogenic bone marrow cells or bone marrow cell-derived osteoblasts can induce more bone around allografts, compared with the simple implantation of allografts.