2017 年 7 巻 1 号 p. 59-65
Purpose Osteoporosis is a progressive and debilitating metabolic bone disease characterized by low bone mass and structural deterioration leading to increased bone fragility. Carbonated hydroxyapatite cement can be a potential biomaterial to be used as a drug carrier. We reported previously that sustainable release of simvastatin (SIM) from poly (lactic-co-glycolic acid) (PLGA) formulations could induce bone formation. The aim of this study was to develop a SIM-loaded PLGA microspheres (SPMs)/self-setting carbonated hydroxyapatite (CHAP) composite, and investigate the effect of SIM released from that composite in comparison with a SIM/CHAP composite used as a control. Methods SPMs were prepared by O/W emulsion technique. The self-setting CHAP cements were fabricated using the cement powder consisted of tetraclcium phosphate (TTCP), dicalcium phosphate dehydrate (DCPD) and NaHCO3. The SIM release from SPMs, SIM/CHAP and SPMs/CHAP cement composite scaffolds in simulated body fluid solution were determined by UV spectrometer. Cell proliferation was determined using WST-8 assay. SPMs, SIM/CHAP and SPMs/CHAP cement composite scaffolds were put into 96 well plate. MC3T3-E1 cells were seeded at 5.0 × 103 cells/well and cultured for 1, 2, 3, 4 weeks. In addition, alkaline phosphatase activity was evaluated after 7, 14, 21 days culture. Results X-ray diffraction analysis (XRD) and Fourier-transformed infrared spectroscopy (FT-IR) results showed most parts of the cement bulk powder transformed into carbonated hydroxyapatite. The SPMs and SPMs/CHAP were able to produce sustained release of SIM for 1 month, whereas the SIM/CHAP released SIM for 2 weeks. The proliferation of MC3T3-E1 cells on the SPLGAMs/CHAP showed no significant difference in comparison with the SIM/CHAP. However, the SPLGAMs/CHAP significantly increased alkaline phosphate activity, a differentiation marker of MC3T3-E1 cells, compared with the SIM/CHAP. Conclusion This study showed that the SPLGAMs/CHAP could release SIM sustainably and induce proliferation and differentiation of MC3T3-E1 more effectively than the SIM/CHAP.