Osteoarthritis is a painful joint debilitating disease currently affecting 20% of Americans - predominately the elderly. Patients often require artificial joint implants to relieve pain and restore mobility. However, 10-30% of these implants fail prematurely due to loosening from Osteolysis or bone resorption and necessitates costly and difficult revision surgery. Submicron UHMWPE wear debris (from implants) has been recognized as the chief etiologic agent responsible for an inflammatory response that leads to Osteolysis development. Recently, a submicron contaminant (MgSi fibers) with unknown inflammatory capabilities has been detected in UHMWPE and may play a role in Osteolyis development. The overall objective of this project is the elucidation of the effect MgSi and UHMWPE debris on macrophage stimulation and related cyto-skeletal reorganization (stiffness) leading to release of pro-inflammatory mediators.
The specific aims proposed to meet this challenge are: 1) Characterization of the abundance, size and shape of Magnesium Silicate (MgSi) debris from postoperative, enzyme digested, joint capsule tissue. 2) Determine the most stimulatory submicron debris (MgSi or UHIVIWPE) through comparative, quantitative assay of cytokine levels. 3) Correlate time- dependent cyto-skeletal stiffness and remodeling features with parallel time frame cytokine levels. The technical methods used to accomplish these aims are cell culture, and assay (ELISA), Fluorescence microscopy, AFM, nano indentation, scanning electron microscopy (SEM) and energy-dispersive x-ray (EDX). This work seeks to improve healthcare by giving insight into complex, debris mediated, immune cell signaling processes and possibly suggest pharmaceutical based strategies to block signaling pathways leading to cytokine release and Osteolysis.
