PARTICULATE BIOMATERIAL INDUCED BONE RESORPTION

金属和聚合物材料的全关节置换术 为数百万人提供了戏剧性的疼痛缓解和功能改善 终末期关节炎患者的比例。尽管联合银行取得了成功 有无假体周围骨溶解的置换手术 无菌松动危及两种水泥的长期成功 和非骨水泥全关节置换术。来自以下来源的颗粒碎片 假体和骨水泥(如果存在)被吞噬，它是 相信这些微粒会激活巨噬细胞和成骨细胞 (可能还有成纤维细胞)产生刺激骨骼的因子 再吸收。 为了支持这一假说，已经证明来自 假体周围肉芽肿组织和巨噬细胞系 颗粒物刺激产生高水平的细胞因子/生长 与骨量增加相关的因素和前列腺素E/2 器官培养中的吸收。我们建议调查这一假说 通过研究分子和细胞水平的因素，可能 触发、维持和/或调节颗粒诱导的假体周围 骨溶解。我们将确定最有效的颗粒物种类 它们在体外激活“标准”细胞系，并将这些细胞系 活化细胞在体内定位的发现(在存在的情况下 微粒)在假体周围溶骨性病变中测量 选择“骨吸收”细胞因子、金属蛋白酶和PGE/2组。 此外，假体周围组织的细胞将被分离， 表征了它们表达骨吸收药物的能力 将会被确定。 这项提议将集中在三个尚未被理解的方面。 种植体相关的假体周围骨溶解：(1)是否存在显性 对骨吸收有刺激作用的颗粒物，还是 处理多个颗粒物之间的协同作用？(2) 是否有一种对磨损刺激做出反应的主要细胞类型 碎屑还是颗粒物引起的骨吸收是一种复杂的机制 同时涉及多种细胞类型(巨噬细胞、成纤维细胞、 巨细胞、成骨细胞和破骨细胞)？以及(3)有没有共同的 细胞水平的调节机制导致假体周围 骨水泥型和非骨水泥型全髋关节置换术中的骨溶解？使用 关于第一个问题，应该强调的是，答案可能 对未来植入物的设计、制造和 材料选择。关于第二和第三个问题，有 是缺乏这样的信息，这被认为是对 发展预防、延缓或逆转的治疗方式 种植体相关假体周围骨溶解。

Total joint replacement with metallic and polymeric materials has provided dramatic relief of pain and improvement in function for millions of patients with end stage arthritis. Despite the success of joint replacement surgery, periprosthetic osteolysis in the presence or absence of aseptic loosening jeopardizes the long-term success of both cemented and cementless total joint replacements. Particulate debris derived from the prosthesis and (when present) bone cement is phagocytized, and it is believed that these particulates activate macrophages and osteoblasts (and perhaps fibroblasts) to produce factors which stimulate bone resorption. In support of this hypothesis, it has been demonstrated that cells from the periprosthetic granulomatous tissues and macrophage cell lines stimulated with particulates yield high levels of cytokines/growth factors and prostaglandin E/2 (PGE/2) associated with increased bone resorption in organ cultures. We propose to investigate this hypothesis by studying factors at the molecular and cellular levels which may trigger, maintain and/or regulate particulate-induced periprosthetic osteolysis. We will determine the most effective particulate species which activate "standard" cell lines in vitro and correlate these findings with in vivo localization of activated cells (in the presence of particulates) in the periprosthetic osteolytic lesions measuring a select group of "bone resorbing" cytokines, metalloproteinases and PGE/2. In addition, cells of the periprosthetic tissue will be isolated, characterized and then their ability to express bone resorbing agents will be determined. This proposal will concentrate on three as yet poorly understood aspects of implant-associated, periprosthetic osteolysis: (1) is there a dominant particulate species which is the stimulus to bone resorption or is this process a synergistic interaction among multiple particulate species? (2) Is there a dominant cell type which responds to the stimulus of wear debris or is the particulate-induced bone resorption a complex mechanism involving simultaneously multiple cell types (macrophages, fibroblasts, giant cells, osteoblasts and osteoclasts)?, and (3) is there a common regulatory mechanism at the cellular level which leads to periprosthetic osteolysis in cemented and cementless total hip arthroplasties? With regard to the first question, it should be stressed that the answer may have important implications for future implant design, fabrication and material selection. With regard to the second and third questions, there is a dearth of such information, which is deemed critical for the development of therapeutic modalities to prevent, retard or reverse implant-associated periprosthetic osteolysis.