Development of bioactive bone grafting for periprosthetic osteolysis

骨溶解是关节置换术后的一个挑战性问题。本研究的目的是分析骨溶解的机制，并制定有效的治疗这种情况。在2002年，我们使用小鼠颅骨骨溶解模型发现聚乙烯和钛颗粒比氧化铝和氧化锆颗粒诱导更多的骨溶解。我们还发现，炎症细胞因子TNF-α、IL-1β、IL-6参与了这种情况。在软骨内成骨的实验中，我们发现b-FGF，一种可以增加成骨细胞增殖的细胞因子，在体内抑制软骨内成骨。2003年，我们评估了聚乙烯、钛和钴铬颗粒诱导的骨溶解程度以及TNF-α、IL-1β、RANKL、OPG随时间的表达。在本实验中，我们发现颗粒诱导破骨细胞生成有两种不同的机制。在分析颗粒诱导的骨质溶解的同时，我们进行了动物研究，以开发用于治疗骨质溶解的生物活性骨移植。将自体骨髓细胞或骨髓细胞源性成骨细胞与携带支架和细胞因子的同种异体骨移植物一起植入大鼠骨缺损中。在本实验中使用了两种类型的同种异体移植物;结构性或颗粒状同种异体移植物。放射学和组织学评估表明，无论是植入自体骨髓细胞或骨髓细胞衍生的成骨细胞可以诱导更多的骨周围同种异体移植物，与单纯植入同种异体移植物。

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.