Subacute systemic toxicity assessment of beta-tricalcium phosphate/carboxymethyl-chitin composite implanted in rat femur.

The efficacy of a composite of beta-tricalcium phosphate particles and carboxymethyl-chitin (beta-TCP/CM-chitin) for bone repair has already been established in animal experiments. In the present study, subacute systemic toxicity was evaluated to further assess the biological safety of the implanted composite. beta-TCP/CM-chitin (approximately 4 mg/kg and 7 mg/kg in male and female rats, respectively) was implanted for 28 days into penetrating defects (2 mm diameter) made artificially in the shaft of the right femur of rats. Sham operation groups with the defect only were prepared as controls. Haematology, blood chemistry, urinalysis, and the histopathology of 44 organs and tissues were investigated. Body weight measurements and clinical observations were performed daily throughout the study. No subacute systemic toxicity possibly caused by the implantation of beta-TCP/CM-chitin was detected. These findings indicate that beta-TCP/CM-chitin composite is a highly biocompatible bone substitute, at least with an implantation dosage of < 4-7 mg/kg.