Phagocytosis of particulate wear debris from arthroplasties by macrophages induces an inflammatory
response that has been linked to implant loosening and premature failure of artificial joints. Inflammatory
mediators released by phagocytic macrophages such as tumor necrosis factor-a (TNF-α), interleukin-1β
(IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) are believed to play a central role in the pathogenesis
of aseptic loosening. The objective of this study was to characterize titanium alloy particulates that closely match
wear debris found around joint arthroplasties and to study their effects on the biosynthesis of inflammatory
mediators by cultured monocytes. Peripheral blood monocytes were isolated from healthy human volunteers.
Monocytes were cultured in 96-well plates for 24 h, washed, and exposed to three concentrations of titanium
particulates and controls from 18Ð24 h. Supernatants were assayed for TNF-α, IL-1β, IL-6, and PGE2 activity.
Energy dispersive X-ray spectroscopy (EDX) verified the titanium alloy to be Ti6A14V. Scanning electron
microscopy (SEM) analysis showed significant titanium particulate heterogeneity with approximately 95% of
the particles <1 micrometer in diameter. SEM and EDX technology was useful in the characterization of the titanium
particulates utilized for in vitro models of titanium-induced cytokine release by monocytes. Incubation of
titanium particulates (in concentrations similar to those found around loosened prosthetic joints) with cultured
monocytes significantly increased their production of TNF-α, IL-1β, and PGE2.