The Effect of Ifosfamide and Mifamurtide Loaded Cement on The Viability of Osteosarcoma Cells

Abstract

Purpose: Despite the good results of neoadjuvant chemotherapy used in the treatment of osteosarcoma, post-operative recurrences continue to be a common problem. It is important to seek new approaches to prevent recurrence in post-operative patients and to eliminate the disadvantages of systemic chemotherapy. The study aims to examine the effects of chemotherapeutic (ifosfamide) and immunotherapeutic (mifamurtide) agents, which are adsorbed into cementum in vitro, on the viability of the osteosarcoma cell line K7M2. Methods: After the K7M2 osteosarcoma cell line was cultured, the cells were adhered to and became 70% confluent, and the supernatants were removed, taking care not to lose the cells. Different doses of ifosfamide (10 ug/ml, 20 ug/ml, 40 ug/ml) alone and with cement; Different doses of mifamurtide (0.25 μg/ml, 0.5 μg/ ml, 1 μg/ml) were given by co-culture with mononuclear cells alone and with cement. Cement was used as the control group. Cell viability was determined by WST after the plate was placed in a 37°C 5% CO2 incubator for 24 hours and 48 hours. Results: It was determined that ifosfamide and mifamurtide in cementum were released into the environment compared to the agent alone, causing more cytotoxic effects in osteosarcoma cells at 24 hours. While an increased effect at 48 hours was observed in mifamurtide, it was not detected in the ifosfamide plus cement group compared to the ifosfamide group alone. Conclusion: Our findings support that local application of ifosfamide and mifamurtide in bone cement may be effective in preventing local recurrence of osteosarcoma after surgery; while filling bone defects resulting from excision surgeries. Among post-operative biomaterials, local therapy may be an additive treatment option in preventing recurrence in osteosarcoma by interacting directly and with the microenvironment.