COMBINED EFFECTS OF POLYETHYLENE WEAR PARTICLE SIZE AND DOSAGE ON MACROPHAGE RESPONSES

Abstract

Ultrahigh molecular weight polyethylene (UHMWPE) wear particles-induced osteolysis and aseptic loosening is the main reason causing the failure of the total joint replacement. It is believed that cytokines, such as tumor necrosis factor-α (TNF-α), released by macrophages that are stimulated by UHMWPE particles can activate osteoclasts and facilitate osteolysis. In one of our previous studies, we have attempted to explain the effects of wear particles on bioactivity by analyzing the phagocytosis of particles from a biophysical viewpoint. By integrating the membrane surface areas of macrophages, we were able to estimate the maximum number of internalized particles, which is defined as the phagocytic capacity for a particle population. It has been found that for the particles with same total volume, the elongated particles have a smaller phagocytic capacity in comparison to the spherical particles. By further analyzing the cell culture and results of animal tests as reported in the literature, we found that the ratio of the particle concentration (no. of particles/no. of cells) to the phagocytic capacity is a critical value for the particles-induced biological responses. When this ratio is smaller than unity, the bioactivity is approximately proportional to the ratio itself; but limited change of biological response was observed when this ratio is larger than unity. In this study, we obtained further experimental evidence in support of this hypothesis. The proliferation and TNF-α release of macrophages when co-cultured with different dosages of UHMWPE particles in an inverted in vitro cell culture model were measured.