Preparation And Osteogenesis Of Controlled-release Electrosprayed Ng-loaded Microspheres/SAIB Hybrid Depots

Reconstruction of oral and maxillofacial bone defect under osteoporosis is a difficult problem faced by dental clinicians.The burst release of drug in osteogenic materials is usually not beneficial to osteogenesis in bone tissue engineering.In this study,after the polymer solutions made by PEG-b-PCL and PCL dissolved in chloroform were magnetically stirred,the influence of the content of PEG-b-PCL,flow rate,voltage on the morphology,size,and size distribution of microspheres were investigated by electrospraying,as well as the influence of PEG-b-PCL on hydrophilicity of microspheres,and the dispersion of the microspheres in water was investigated.The morphology and size distributions of electrosprayed Ng-microspheres were characterized by scanning electron microscopy(SEM).The Ng-microspheres and Ng-m-SAIB depots were characterized by SEM,Fourier transform infrared spectroscopy(FTIR)and in vitro release studies.In vitro osteoblast-microsphere interactions and in vivo osteogenesis after implantation of Ng-m-SAIB depots were assessed respectively.Results showed that monodispersed spherical microspheres with average particle sizes ranging from 5 to 6 ?m and the coefficient of variation ranging from 15%~21% could be fabricated when the content of PEG-b-PCL was 10%~20%,flow rate was 1ml/h,and voltage was 10 kV.Microspheres along with fibers could be fabricated when the content of PEG-b-PCL was 30%.The contact angle of the microspheres decreased from 126.2±4.8° to 29.9±4.9° when the content of PEG-b-PCL increased from 0% to 20%,and the differences have statistical significance(p < 0.05),which meaned that changing the content of PEG-b-PCL could improve the hydrophilicity of the microspheres.In the meantime,microspheres with 10% ~ 20% PEG-b-PCL could form homogeneous dispersions in water.The addition of sucrose acetate isobutyrate(SAIB)to monodisperse Ng-microspheres did not cause a change in the chemical structure.The performances of the microspheres in osteoblast-microsphere interactions were better when the naringin content was 4% than when it was at 2% and 6%.On the first day following the loading of Ng-microspheres(2%,4%,and 6%)into SAIB depots,the burst release was reduced dramatically from 70.9% to 6.3%,73.1% to 7.2%,and 73.9% to 9.9%,respectively.In addition,after 8 weeks,the new bone formation rate in the calvarial defects of SD rats receiving Ng-m-SAIB was 53.1% compared to 21.2% for the control group and 16.1% for the microsphere-SAIB group.These results demonstrated that monodispersed microspheres with improved hydrophilicity could be fabricated by PEG-b-PCL/ PCL and that Ng-m-SAIB hybrid depot may have promise in bone regeneration applications and may become a kind of bone substitute material with excellent sustained-release properties.