Effect of polymer molecular weight and addition of calcium stearate on response of MG63 osteoblast-like cells to UHMWPE particles

Periprosthetic osteolysis and implant loosening is associated with the pres ence of ultrahigh molecular weight polyethylene (UHMWPE) wear debris partic les. Osteoblast phenotypic expression in vitro is affected by UHMWPE partic les, suggesting that bone formation may also be affected by wear debris. He re we tested the hypothesis that the response of osteoblasts to UHMWPE can be modified by changes in UHMWPE particle chemistry. We used four different commercially available preparations of GUR UHMWPE particles to determine i f chemical composition (+/-Ca-stearate) or polymer molecular weight (3.1-4. 2 million or 5.4-6.5 million g/mol) modulates osteoblast response. Particle s were characterized by size distribution, morphology, and number of partic les added to the culture medium. They had an average equivalent circle diam eter ranging from 0.46-1.26 mum. MG63 cell response was assessed by measuri ng cell number, cellular and cell layer alkaline phosphatase, and prostagla ndin E-2 (PGE(2)) production. There were dose-dependent effects of the part icles on cell response. Cell number and PGE(2) production were increased, w hile alkaline phosphatase specific activity was decreased. In addition, the re was a marked difference between cultures treated with particles containi ng Ca-stearate and as a function of polymer molecular weight. Particles of higher molecular weight caused a greater stimulation of proliferation and i nhibition of alkaline phosphatase than particles of lower molecular weight. The presence of Ca-stearate exerted a more pronounced depression of osteob last phenotype as well as a significantly greater increase in PGE(2) releas e by the cells. The present study shows that chemical composition and polym er molecular weight of UHMWPE are capable of modulating osteoblast response to particles. The results suggest that osteoblast differentiation is inhib ited by UHMWPE particles, whereas cell proliferation and PGE(2) production are stimulated. This may have direct effects on osteoblasts and bone format ion, but also paracrine effects on cells of the monocytic lineage inducing bone resorption and promoting inflammation which may lead to aseptic loosen ing. The present results suggest that the cellular events in aseptic loosen ing may be modulated or even accelerated by changes in the composition of t he UHMWPE used to fabricate implants. (C) 2001 Orthopaedic Research Society . Published by Elsevier Science Ltd. All rights reserved.