Acute toxicity of metal ions in cultures of osteogenic cells derived from bone marrow stromal cells

The effects of metal ions released from orthopedic implants on nearby bone cells remain largely unknown. The purpose of this study was to examine the acute toxicity of metal ions on osteogenic cells derived from bone marrow. Bone marrow stromal cells were cultured with metal ions found in commonly used orthopedic implants, that is, Ti-6Al-4V, Co-Cr-Mo, and 316L stainless steel. Solutions of individual ions and combinations representing the alloy composition were prepared from atomic absorption standards and added to the cultures to give concentrations ranging from 50 ppb to 50 ppm. After a 48-h period of exposure to ions, the bone marrow cultures were examined for effects of cytotoxicity by measuring total cell number, total cell protein, and mitochondrial activity. Cr⁶⁺ was grossly cytotoxic; Co²⁺, Mo⁶⁺, Fe³⁺, and Ni²⁺ were moderately cytotoxic; and Ti⁴⁺, Al³⁺, V⁵⁺, and Mn²⁺ were minimally toxic, as determined by the assays used. Ion solutions representing Co-Cr-Mo and 316L stainless steel were moderately toxic; solutions representing Ti-6Al-4V were toxic at only the highest concentrations used. The observed cytotoxicity was time-dependent, with irreversible toxic effects being initiated following as short as a 3- to 6-hour exposure. These results show that metal ions associated with Co-Cr-Mo and 316L stainless steel are toxic to osteogenic cells at concentrations approximating those measured in the fibrous membrane encapsulating orthopedic implants.