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Titanium particles derived from the wear of the orthopaedic implant surfaces can activate macrophages to secrete cytokines and stimulate osteoclastic bone resorption, causing osteolysis around orthopaedic implants. However, what happens to the titanium particles after being phagocytosed by macrophages is not known. We prepared titanium particles (as received, clean, and LPS-coated), and exposed them to macrophages in culture. Free particles were washed away after 24 h and the intracellular particles were kept in culture for additional 48 h until being harvested by lysing the cells. Particles that had been cell treated or noncell treated were examined by scanning electronic microscopy to analyze the shape, size, and concentration of the particles. The cell treated and noncell treated particles were exposed to macrophages in culture with a particle to cell ratio of 300:1. After 18 h, the levels of TNF-alpha in culture medium and the viability of the cells were examined. Clean particles did not stimulate TNF-alpha secretion by macrophages, while LPS-coated particles dramatically increased that response. Phagocytosis by macrophages did not change the shape and size of the particles, but depleted the ability of the particles to stimulate TNF-alpha secretion by macrophages. This indicates that macrophages are capable of rendering titanium particles inactive without degrading the particles, possibly by altering the surface chemistry of the particles.

It is still unknown if wear-debris particles themselves induce osteolysis or if they serve a functional role as receptors for ligands that incite an inflammatory response that ultimately leads to bone resorption. In this study, commercially pure titanium particles (cpTi) were subjected to a serial combination of different cleaning methods to remove Lipopolysaccharide (LPS) or were incubated in LPS solutions of known concentrations. Then, the response of the macrophage cell line IC-21 to the cleaned particles, LPS-bound Ti particles, and soluble LPS was examined. It was found that cleaned particles up to 1000 particles per cell did not stimulate macrophages to release Tumor necrosis factor-alpha (TNF-α) or Interleukin 6 (IL-6), but they significantly increased the release of Prostaglandin E2 (PGE2) when the particle concentration was higher than 500 particles per cell. At one particle per cell, Ti particles bound with LPS stimulated the release of IL-6 and TNF-α by macrophages. The level of released cytokines was dependent on, and correlated with, the amount of LPS present on the particles. The macrophages were more sensitive to soluble LPS than to particle-bound LPS, and the simultaneous addition of cleaned Ti particles did not have additional effects on the effects of soluble LPS. This study shows evidence that, cpTi particles and LPS have distinct mechanisms of action on the IC-21 macrophages, but that both contribute to the development of an inflammatory response. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006