Biologic effects of cobalt chrome in cell and animal models.

The literature on animal and cellular models used to study the response to cobalt chrome alloy implants and wear and corrosion products is reviewed. Animal studies show that in solid form cobalt chrome alloy is relatively well tolerated. Injections of large numbers of particles in a single bolus lead to acute inflammation and necrosis, followed by a chronic inflammatory response. Macrophages are the predominant cell type and may persist in the tissues for years. Long term studies have failed to confirm the induction of tumors. In vitro studies confirm the toxic effects of cobalt chrome alloy corrosion products and wear particles, especially cobalt, and show that intracellular corrosion is an important mechanism for early release of cobalt ions. In vitro studies show that cobalt chrome alloy particles induce the release of inflammatory mediators from macrophages before causing cell death. These mediators have significant effects on osteoblastlike cells, as well as inducing bone resorption. Variations in the cell types, implantation site, and characteristics of the particles used in experimental models make interpretation of the results difficult. Standardized methods to control for size, shape, and number of particles for testing are proposed. It is important that in vitro and in vivo findings not be taken in isolation, but be compared with the results of human studies.