No abstract

Particulate wear-debris are detected in histiocytes/macrophages of granulomatous tissues adjacent to loose joint prostheses. Such cell-particle interactions have been simulated in vitro by challenging macrophages with particles dosed according to weight percent, volume percent, and number of particles. Each of these dosage methods has inherent shortcomings due to varying size and density of challenging particles of different compositions. In this study we challenged P388D1 macrophages with titania and polystyrene particles (< 2 microns), with dosage based on the ratio of the surface area of the particles to the surface area of the cells. The effect of size and composition on (1) the bone resorbing activity, (2) fibroblast proliferation, and (3) secretion of IL-1 and PGE2 was determined. Macrophage response to particulate debris appears to be dependent on particle size, composition, and dose as given by surface area ratio. P388D1 macrophages challenged with titania particles released IL-1, but did not stimulate fibroblasts. Inhibition of macrophage DNA synthesis at higher surface area ratios suggests cell damage or death. Particle-stimulated cells increased bone resorption up to 125% of controls but released only basal levels of PGE2. Macrophages stimulated by wear particles are expected to synthesize numerous factors affecting events in the bone-implant interface. Using the concept of surface area ratio allows us to study and compare such cellular responses to wear particles in a standardized manner.

We studied the ability of four clinically relevant particle species to stimulate human peripheral blood monocytes to release bone-resorbing agents, including interleukin-1 (both interleukin-1 alpha and interleukin-1 beta), interleukin-6, and prostaglandin E2. The species studied were titanium-6% aluminum-4% vanadium (TiAlV), commercially pure titanium, fabricated ultrahigh molecular weight polyethylene, and polyethylene retrieved from interfacial membranes of failed uncemented total hip arthroplasties. For all species, the mean size was less than 1 micron. Human peripheral blood monocytes were challenged with these particles in a uniform manner on the basis of surface area. Phorbol 12-myristate acetate, zymosan, and nonphagocytosable titanium particles served as controls. Stimulation of human monocytes is a function of the composition and concentration of particles. In this study, TiAlV particles appeared to be the most competent to elicit the synthesis and release of inflammatory mediators. Particles of commercially pure titanium and of fabricated ultrahigh molecular weight polyethylene also could induce the release of various cellular mediators, albeit at a lower level, whereas the particles of polyethylene retrieved from interfacial membranes were less stimulatory in these short-term in vitro experiments.