Characterization and biological effects of wear particles from metal-metal hip implants

Polyethylene wear particles have been the main culprit in initiating osteolysis and aseptic failure of conventional metal-polyethylene total hip arthroplasties. There has been a revived interest in metal-metal (MM) bearings, made of CoCrMo alloys; because of their very high wear resistance compared with conventional bearings. The work that forms the basis of this thesis attempts to examine MM bearings as one potential solution to the problem of osteolysis. The results provide important new information on MM particle characteristics and their effects on tissue, as well as the effects of their corrosion products (Co2+ and Cr3+) on macrophage response in vitro.An enzymatic protocol for isolation and characterization of metal particles was first developed in order to minimize particle changes due to the reagents. Metal particles isolated from a hip simulator and from human tissues around MM implants using this protocol were found to be mainly round to oval and more occasionally needle-shaped, extremely small (∼50 nm), and surprisingly, mostly chromium oxides. In vitro and in vivo run-in wear periods did not exactly correlate, but MM wear particles from both sources were quite similar at specific periods of comparison. Alloy composition and number of running cycles in vitro influenced the overall characteristics of the particles, although the observed differences were relatively small and would probably not induce a difference in the biological response.Tissue response to metal wear particles revealed the presence of IL-1beta and IL-6, two major inflammatory mediators implicated in periprosthetic osteolysis. There was also a high correlation between the amount of these cytokines and the quantity of metal particles. The amounts of cytokines decreased when the quantities of particles increased, most likely due to the high toxicity of the metal particles when present in larger quantities. There was more IL-6 than IL-1beta and TNF-alpha remained at low levels. Apoptosis was clearly observed in some tissues from the patients analyzed, but results were highly variable depending on the tissues analyzed. More patients would be necessary to complete this study on apoptosis.In vitro, Co2+ and Cr3+ ions induced the secretion of TNF-alpha, another major inflammatory mediator implicated in periprosthetic osteolysis, and macrophage mortality in a dose- and time-dependent manner. Co2+ was more toxic than Cr 3+. Macrophage apoptosis was predominant at 24h with both ions, and with the lowest concentrations at 48h. Necrosis was more prevalent with the highest concentrations at 48h. The implication of caspase-3 pathway was also identified in macrophage apoptosis. These results suggest how specific therapeutic treatments could modulate macrophage response to these ions