Fabrication Of Sr-or Cu-Doped Hollow Bioactive Glass Nanofibrous Scaffolds For Controlled Drug Delivery

Millions of patients across the country need bone graft repair every year,bone scaffold materials with excellent performance in bioactivity,biocompatibility,biodegradability,and mechanism are urgently needed in clinical treatment of bone defect.Moreover,the plasma concentration of traditional drug administration fluctuates greatly in human body and the utilization ratio of drug is low.Therefore,it has become an urgent problem to prepare new composite bone scaffold materials for controlled drug delivery.Hollow bioactive glass nanospheres(HBGNs)have good bioactivity and its unique microstructure can make it control the drug delivery behavior.Sr or Cu-doped hollow bioactive glass nanospheres(Doped-HBGNs)also has the properties of osteostimulation,angiogenesis capacity or antibacterial activity,which can be better applied to the treatment of bone defect.In this article,doped hollow bioactive glass drug-loading nanospheres(VAN@Doped-HBGNs)were choose as drug carrier and were combined with silk fibroin(SF)with excellent adsorption and biological properties,to prepare new organic/inorganic composite bone scaffold materials for controlled drug delivery,and study systematically controlled drug delivery and biological activity in vitro.Specific research contents are as follows:(1)Preparation and biological activity in vitro of Doped-HBGNs.Doped-HBGNs were prepared with sol-gel method by using polyacrylic acid(PAA)as the template and strontium or copper sources replaced part of calcium sources.The influence of Sr,Cu doping on the morphology,structure,element composition and thermal property of Doped-HBGNs were further studied,and the SBF solution immersion method was used to evaluate its biological activity in vitro.The results showed that the controlled doping of Doped-HBGNs could be realized through replacing the corresponding molar ratios of CaO component with different molar ratios of SrO or CuO component.Doped-HBGNs had hollow spherical structure,smooth surface,uniform particle size and good dispersibility,while its particle size decreased,pore volume,pore size,along with specific surface area increased,and itsthermal property became more stable after doping.Its biological activity could be improved under appropriate concentration(no more than 10 mol%)of Sr and Cu doping.(2)The controlled drug delivery and biological activity in vitro of VAN@Doped-HBGNs.The controlled drug loading and release of VAN@Doped-HBGNs at different drug concentrations or different pH value and temperature were studied,respectively,by selecting Vancomycin hydrochloride(VAN)as the model drug molecules and Doped-HBGNs as drug carrier.And the SBF solution immersion method was also used to evaluate its biological activity in vitro.The results showed that the drug loading efficiency of VAN@Doped-HBGNs could be effectively adjusted by drug concentration,and its drug release behavior was pH and temperature sensitive.The drug loading efficiency,release rate and cumulative release rate of VAN@HBGNs and VAN@5Sr-HBGNs were obviously higher than VAN@5Cu-HBGNs,and its slow release time was more durable.Its biological activity could be improved as the loading of VAN molecules.(3)Fabrication and the properties in vitro of VAN@Doped-HBGNs/PEO/SF nanofibrous scaffolds.VAN@Doped-HBGNs/PEO/SF nanofibrous scaffolds were fabricated though electrospinning technique.The effects of Sr doping on its morphology,structure and its controlled drug release in specific pH value and temperature were further studied,and the SBF solution immersion method was also used to evaluate its biological activity in vitro.The results showed that the fibers of drug-loading nanofibrous scaffolds were complete and continuous,uniform in thickness and smooth in surface,and the doping of Sr had no obvious influence on its appearance.Drug-loading nanofibrous scaffolds could realized continuous release for VAN,and its drug release behavior is pH sensitive.The drug cumulative release rate of VAN@5Sr-HBGNs/PEO/SF was lower than VAN@HBGNs/PEO/SF,but its drug release rate in the early stage was lower and slow release time was more durable.Its biological activity could be improved under 5 mol% doping concentration of Sr.In conclusion,as-prepared VAN@Doped-HBGNs/PEO/SF nanofibrous scaffolds had good biological activity and could realize controlled drug loading and release,may even had the properties of osteostimulation,angiogenesis capacity or antibacterial activity,which made it have potential as new bone scaffold materials with controlled drug delivery applied in the biomedical sciences.