Heparin-conjugated Sr-nHAp/silk Fibrin Scaffold For Sustained Release Of BMP-2 And Its Application In Bone Regeneration

The development of tissue engineering and regenerative medicine provides new ideas and methods for clinical repair and treatment of bone defects.Bone tissue engineering scaffold is one of the key elements in bone tissue engineering technology,and its preparation method and function are of great concern.An ideal bone repair scaffold material generally meets the following characteristics: excellent biocompatibility,moderate biodegradation rate and certain mechanical properties.It is difficult for a single material to meet clinical requirements.Therefore,the materials were modified to prepare the composite scaffolds with loaded growth factors.However,growth factors are generally unstable and easily deactivated.Therefore,the design of a kind of bone tissue engineering scaffold that can sustain release growth factor slowly to repair bone defect is proposed,which provides a new idea to solve the current clinical problems.In this study,Sr-nHAp was selected as the inorganic component of the scaffold for bone tissue engineering and SF was used as a natural polymer to provide support.The composite scaffolds were prepared by mixed the suspension solution of different strontium content of hydroxyapatite into the SF solution.Microstructures of the scaffolds were observed by scanning electron microscopy(SEM).The thermal stability,mechanical properties and mineralization of composite scaffolds were characterized by thermogravimetric analyzer,universal testing machine and immersing in simulated body fluids.In addition,the results of the cell experiment showed that all scaffolds held good biocompatibility.The above results indicated that the 10%Sr-nHAp/SF scaffold possessed good thermal stability,mechanical properties,mineralization and contributed to proliferation,adhesion and differentiation of cell.Bone morphogenetic protein(BMP-2)was loaded on a composite scaffold to enhance the osteoinduction and osteogenic properties.To the sustained release of BMP-2,heparin was conglutinated to the Sr-nHAp/SF composite scaffold and then loaded with BMP-2.Next,the Sr-nHAp/SF-Hep-BMP-2 composite scaffold was evaluated by release experiments,alkaline phosphatase(ALP)activity,osteocalcin(OCN)and osteopontin(OPN)expression.The Sr-nHAp/SF-Hep-BMP-2 composite scaffold was implanted into the cranial defect of rats,and the ability of the composite scaffold for repairment the cranial defect in rats was evaluated by micro-CT and histological staining analysis.In summary,the Sr-nHAp/SF-Hep-BMP-2 composite scaffold has good biocompatibility,thermal stability,mechanical properties,and mineralization ability.In addition,the composite scaffold has ability to control the release of BMP-2.In addition,Sr-nHAp enhanced its biological activity in composite scaffolds,indicating that the composite scaffold prepared in this study has great potential in the field of bone tissue engineering.