Effects of soluble metals on human peri-implant cells

Despite reports associating tissue necrosis with implant failure, the degree to which processes, such as metal toxicity, negatively impact implant performance is unknown. We evaluated representative human peri-implant cells (i.e., osteoblasts, fibroblasts, and lymphocytes) when challenged by Al+3, Co+2, Cr+3, Fe+3, Mo+5, Ni+2, and V+3 chloride solutions (and Na+2 as a control) over a wide range of concentrations (0.01-10.0 mM). Cell responses were measured using proliferation assays, viability assays, and microscopic cell morphology assessments. Differential effects were found to be less a function of the cell type than of the composition and concentration of metal challenge. No preferential immunosuppression was demonstrated. Below 0.01 mM, no metal was toxic. The most toxic metals (i.e., Co, Ni, and V) reduced proliferation (IC50), and viability (LC50) and cell morphology of osteoblasts, fibroblasts, and lymphocytes by <50% at challenge concentrations <1 mM. All other metals tested required >5 mM to exact the same responses. Below 1 mM, these toxic metals also induced alterations in all cell morphology consisting of loss of filopodia or lamellipodia or changes in cell shape. Metals that were toxic at clinically relevant concentrations (less than previously reported values in peri-implant tissues/fluids) include Co (0.6 mM), Ni (0.8 mM), V (0.5 mM) for lymphocytes and Co (0.8 mM), V (0.3 mM), Al (1-5 mM), Fe (1-5 mM) for fibroblasts, and Co (0.8 mM), Ni (0.7 mM), V (0.1 mM) for osteoblasts. Only Co and V were toxic in vitro at concentrations below that detected in vivo in synovial fluid (V at 0.1 mM and Co at 0.8 mM for fibroblasts, and V at 0.4 mM and Co at 0.8 mM on osteoblasts). Thus, soluble Co and V released from Co- and Ti-based alloys, respectively, could be implicated as the most likely to mediate cell toxicity in the periprosthetic milieu.