Proliferation and differentiation of MC3T3-E1 cells on polymethyl methacrylate cements containing Fe3O4 and TiO2 for hyperthermic treatment of metastatic bone tumors.

Abstract

Polymethyl methacrylate (PMMA) bone cement is widely used to relieve pain caused by metastatic bone tumors. We previously found that PMMA bone cement containing 15 mass% or more of TiO₂ showed good apatite-forming ability, and 25 mass% or more of Fe₃O₄ generated sufficient heat for hyperthermia under an alternating current (AC) magnetic field. In this study, the cytocompatibility of PMMA bone cement with Fe₃O₄:TiO₂ weight ratios of 25:15 (F25T15-3/2-42) and 30:15 (F30T15-3/2-42) was evaluated using osteoblastic cells (MC3T3-E1). The proliferation and differentiation of MC3T3-E1 cells were suppressed for F25T15-3/2-42 and F30T15-3/2-42 compared to PMMA bone cement without Fe₃O₄ and TiO₂ (F0T0-3/2-42). The release of methyl methacrylate (MMA) monomers from F25T15-3/2-42 and F30T15-3/2-42 at 7 days was about 33 and 50 times higher than that from F0T0-3/2-42, respectively. The remarkable release of MMA monomers from F25T15-3/2-42 and F30T15-3/2-42 may be responsible for the suppressed proliferation and differentiation of MC3T3-E1 cells. The release of MMA monomers was not reduced when the MMA/PMMA weight ratio was decreased from 3/2 to 1/1, however, it was significantly reduced by increasing the content of benzoyl peroxide (BPO) and N, N-dimethyl-p-toluidine (DMPT) to 8 and 4 mass% against MMA, respectively. Proliferation and differentiation of MC3T3-E1 cells on PMMA-type cements containing Fe₃O₄ and TiO₂ with increased BPO and DMPT contents need to be investigated in the future; however, our findings will be useful for designing PMMA cements for the hyperthermic treatment of metastatic bone tumors.