CELLULAR MECHANISMS OF IMPLANT LOOSENING

描述(改编自申请人的摘要)：松动 骨科植入物是一个严重的问题，会导致疼痛、丧失 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磨屑引起的骨溶解引起的， 对这一过程中涉及的机制的理解对于 开发防止种植体松动的新方法。各种研究 说明磨损颗粒会导致骨溶解。其中包括组织学 对修正的植入物周围组织的检查，特征 在这类组织中发现的磨损颗粒和骨吸收的测量 对粒子作出反应而产生的细胞因子。然而，细胞因子 抑制骨吸收也可能产生。因此，不可能 为了先验地预测，混合的因素是否会对 磨损颗粒可能会对 骨吸收。假设特定的细胞相互作用和 细胞因子在刺激骨吸收中起重要作用 磨粒。本应用程序侧重于记录这些重要的 流程。颗粒组成、大小、形状和表面化学可能 调节这类颗粒对骨吸收的影响。因此，粒子 各种不同的作文将会被检查。应用程序的 因此，具体目标是：1)评估矫形外科佩戴的效果 碎屑对骨吸收的影响；2)测定参与骨吸收的细胞因子 骨科磨屑对骨吸收的刺激；以及3) 确定参与刺激骨吸收的细胞类型 整形外科的磨损碎片。

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.