Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition

Wear debris is considered to be one of the main factors responsible for ase ptic loosening of orthopaedic endoprostheses. Whereas the response of cells in the monocytic lineage to foreign materials has been extensively studied , little is known about cells at the bone formation site. In the present st udy, we examined the hypothesis that the response of osteoblasts to wear de bris depends on the chemical composition of the particles. We produced part icles from commercially pure titanium (cpTi), Ti-6Al-4V (Ti-A), and cobalt- chrome (CoCr) and obtained ultrahigh molecular weight polyethylene (UHMWPE; GUR 4150) particles from a commercial sourer. The equivalent circle diamet ers of the particles were comparable: 1.0 +/- 0.96 mu m for UHMWPE; 0.84 +/ - 0.12 mu m for cpTi; 1.35 +/- 0.09 mu m for Ti-A, and 1.21 +/- 0.16 mu m f or CoCr, Confluent primary human osteoblasts and MG63 osteoblast-like cells were incubated in the presence of particles for 24 h. Harvested cultures w ere examined by transmission electron microscopy to determine if the cells had phagocytosed the particles. Particles were found intracellularly, prima rily in the cytosol, in both the primary osteoblasts and MG63 cells. The ch emical composition of the particles inside the cells was confirmed by energ y-dispersive X-ray analysis. Morphologically, both cell types had extensive ruffled cell membranes, less-developed endoplasmic reticulum, swollen mito chondria, and vacuolic inclusions compared with untreated cells. CpTi, Ti-A , and CoCr particles were also added to cultures of MG63 cells to assess th eir effect on proliferation (cell number) and differentiation (alkaline pho sphatase activity), and PGE(2) production. All three types of particles had effects on the cells. The effect on cell number was dependent on the chemi cal composition of the particles; Ti-A and CoCr caused a dose-dependent inc rease, while cpTi particles had a biphasic effect with a maximal increase i n cell number observed at the 1 : 10 dilution. Alkaline phosphatase specifi c activity was also affected and cpTi was more inhibitory than Ti-A or CoCr . PGE(2) production was increased by all particles, but the magnitude of th e effect was particle-dependent: CoCr > cpTi > Ti-A. This study demonstrate s clearly that human osteoblast-like cells and MG63 cells can phagocytose s mall UHMWPE, CoCr, Ti-A, and cpTi particles. Phagocytosis of the particles is correlated with changes in morphology, and analysis of MG63 response sho ws that cell proliferation, differentiation, and prostanoid production are affected. This may have negative effects on bone formation adjacent to an o rthopaedic implant and may initiate or contribute to the cellular events th at cause aseptic loosening by inhibiting bone formation. The effects on alk aline phosphatase and PGE(2) release are dependent on the chemical composit ion of the particles, suggesting that both the type and concentration of we ar debris at an implant site may be important in determining clinical outco me. (C) 2000 Elsevier Science Ltd. All rights reserved.