A Study On Nano-structural Design And Osteoinductivity Regulation Of Silk-hydroxyapatite Bone Materials

Repair of bone defects caused by trauma,infection or tumours resection still persent great challenges.Currently,autologous bone grafting is considered ―gold standard‖.However,limited bone supply and donor site morbidity are main shortcomings that restrict their application in clinical.The emergency of bone tissue engineering provides a new strategy of bone defect repair.Construction of artificial bone with biological characteristics similar to normal bone is a hot topic in bone tissue engineering.Silk fibroin(SF)with outstanding biocompatibility,slowly biodegrability,and mechanical property is a promising matrice in bone tissue engineering.Here,the bioactive bone materials were constructed where water-dispersed hydroxyapatite nanoparticles with silk fibroin as template and stabilizer were used as inorganic phase of natural bone,while silk fibroin(SF)matrix was used as orgnanic phase.The water-dispersed hydroxyapatite nanoparticles(Silk-HA)with silk fibroin as template was used to load bone morphogenetic protein 2(Silk-HA-BMP-2),achieving a controlled release of BMP-2 and inducing osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.These results revealed improved osteoinductivity of the BMP-2-loaded nanoparticles.Then the water-dispersable silk-HA nanoparticles were directly dispersed in SF solution to form uniform mixture.SF-HA composite scaffolds were prepared via freeze-drying process,and showed tunable BMP-2 release behaviors by regulating BMP-2 distribution on the SF-HA composite scaffolds.Improved osteoinductivity was achieved for these scaffolds through optimizing BMP-2 release behaviors.Furthermore,due to severial unique properties including handling properties,filling the site of irregular bone defects effectively,and fewer surgery complications,injecatble bone materials showed good bone regeneration capacity in the repair of irregular bone defects.In our study,we prepared injectable hydrogels by adding the SF-HA nanoparticles to SF nanofiber hydrogel to form uniform mixture.In this hydrogels system,HA particles distributed homogeneously inside SF hydrogels at nanoscale even at higher HA content of above 60%,without the sacrifice of injectable property.The in vitro and in vivo studies indicated that the injectable hydrogels have better osteogenesis ability.In conclusion,artificial bone materials were developed with SF and HA nanoparticles as the elements.These materials showed better osteogenesis capacity through imitating the structure and microenvironment of natural bone,which would provide valuable information for novel scaffold fabrication for bone repair.