Study On Aminated Mesoporous Silica Nanoparticles Enhanced Chitosan/Silk Fibroin Gels And Their Drug Release

Bone injury or bone defect caused by trauma,inflammation,tumor and degenerative disease is one of the common diseases in orthopedics.Autogenous and allogeneic bone transplantation techniques that are commonly used in clinic for the treatment of large-size bone defects are facing various problems such as limited donors,rejection,and disease transmission.Tissue engineering strategy involving in use of scaffolds,seed cells and cytokines for bone repair has shown clinical potential.In addition to commonly used pre-formed porous solid scaffolds in bone repair,hydrogels have also been attracted a lot of interest in the repair and reconstruction of injured bone tissues.Chitosan/glycerophosphate is a kind of thermo-sensitive hydrogel with good biocompatibility in vivo.It is an injectable fluid at room temperature,and can rapidly transform from a sol state to a gel state at physiological temperature and p H.Chitosan/glycerophosphate gel has been widely used for drug release,cell delivery,and tissue repair.However,its shortcomings such as poor mechanical properties and fast degradation in vivo have limited its application in bone tissue engineering.In order to improve the performance of chitosan/glycerophosphate hydrogel,a kind of aminated mesoporous silica nanoparticles were combined with chitosan and silk fibroin for preparing a type of thermo-sensitive chitosan/silk fibroin composite gel using genipin as a covalent crosslinker.Owing to the genipin-involved linkages among the amino groups on the surface of aminated mesoporous silica nanoparticles and the amino groups on chitosan backbone,the resulting composite gels can be significantly enhanced in their strength.In addition,the pores in aminated mesoporous silica nanoparticles can be used to load certain drugs suited for bone repair or reconstruction.Therefore,it is possible to achieve goals for preparation of mechanically strong hydrogels while having an ability to control the drug release.Aminated silica nanoparticles with hierarchical mesopores（HMSNs-NH₂）were firstly prepared by a co-condensation method and used for loading naringin.The naringin load for these nanoparticles was found to reach around 13.4%,and the release profile was seen to reach the plateau phase after 8-hour release.The color change and FTIR characterization of nanoparticles revealed that HMSNs-NH₂ were able to directly react with genipin.HMSNs-NH₂were embedded into the chitosan/silk fbrion hydrogel,and the resulting composite hydrogels were detected to be thermo-sensitive.The transition temperature of the composite gels increased with incremental content of HMSNs-NH₂.The rheological measurements showed that the elastic modulus of composite gels was significantly higher than that for chitosan gel without embedding HMSNs-NH₂.As the content of HMSNs-NH₂ increased,the elastic modulus and pressure-bearing capacity of the composite gels also increased,demonstrating that the incorporation of HMSNs-NH₂makes the composite gels strong and stable.By loading naringin into HMSNs-NH₂and embedding naringin-loaded HMSNs-NH₂into chitosan/silk fbrion gel,the achieved composite gels showed ability to administer sustained naringin release.It was also found that the dry composite gels had well interconnected pores with suitable pore sizes.MC3T3-E1 cells were used as seed cells,and their viability and proliferation were detected using a MTT essay and a live/dead staining method.Results showed that MC3T3-E1 cells were alive and proliferated normally inside the composite gels,indicating that the composite gels have good biocompatibility.These results confirm that chitosan/silk fibroin embedded with HMSNs-NH₂have potential in bone tissue engineering applications.