CELLULAR MECHANISMS OF IMPLANT LOOSENING

描述（改编自申请人的摘要）： 整形外科植入物是一个重要的问题，它导致疼痛， 功能，并最终进行翻修手术。 因为一个重要的原因 无菌性松动似乎是由于磨损碎屑引起的骨质溶解， 了解这一过程所涉及的机制对于 开发新的方法来防止种植体松动。 各种研究 表明磨损颗粒诱导骨质溶解。 这些包括组织学 检查翻修植入物周围的组织， 在这些组织中发现的磨损颗粒，以及骨吸收的测量 响应于颗粒产生的细胞因子。 然而，细胞因子， 也可能产生抑制骨吸收。 因此， 预测，先验，是否混合的因素产生的反应， 磨损颗粒很可能具有净刺激或抑制作用， 骨吸收 据推测，特定的细胞相互作用和 细胞因子在刺激骨吸收中是功能上重要的， 磨损颗粒。 此应用程序侧重于记录这些重要的 流程. 颗粒成分、大小、形状和表面化学可能 调节这些颗粒对骨吸收的影响。 因此，粒子 各种不同的组合物将被检查。 应用程序的 因此，具体目的是：1）评估骨科磨损的影响 2）确定参与骨吸收的细胞因子， 骨科磨损碎屑刺激骨吸收;和3） 确定参与骨吸收刺激的细胞类型， 骨科磨损碎屑。

DESCRIPTION (Adapted from the Applicant's Abstract): Loosening of orthopaedic implants is a significant problem that leads to pain, loss of function, and, ultimately, revision surgery. Since one important cause of aseptic loosening appears to arise from wear debris-induced osteolysis, an understanding of the mechanisms involved in this process is crucial to develop new methods to prevent implant loosening. A variety of studies suggest that wear particles induce osteolysis. These include histological examination of tissue surrounding revised implants, characterization of the wear particles found in such tissues, and measurement of bone resorptive cytokines produced in response to the particles. However, cytokines that inhibit bone resorption are also likely produced. Thus, it is not possible to predict, a priori, whether the mixture of factors produced in response to wear particles is likely to have a net stimulatory or inhibitory effect on bone resorption. It is hypothesized that specific cellular interactions and cytokines are functionally important in stimulation of bone resorption by wear particles. This application focuses on documenting these important processes. Particle composition, size, shape, and surface chemistry likely regulate the effect of such particles on bone resorption. Thus, particles of a variety of different compositions will be examined. The application's Specific Aims are therefore: 1) to assess the effects of orthopaedic wear debris on bone resorption; 2) to determine the cytokines involved in stimulation of bone resorption by orthopaedic wear debris; and 3) to determine the cell types involved in stimulation of bone resorption by orthopaedic wear debris.