| Bone tuberculosis disease is a destructive disease caused by the invasion of bone or joint tissues by tuberculosis bacilli mainly transmitted by blood.Clinically,for the treatment of bone tuberculosis disease,it is generally used to remove the lesion by surgery,then fill the bone tissue defect,and place or long-term oral anti-tuberculosis drugs in the lesion.Commonly used bone defect filling materials can not induce the reconstruction of new tissue and are difficult to degrade in vivo.Placing antituberculous drugs at the lesion through surgery cannot guarantee the long-term effective and stable release of drugs,while local repeated administration increases the pain of treatment for patients.Oral administration is also difficult to ensure that the concentration of drugs in the focal area can reach the optimal antibacterial concentration,and long-term oral administration of drugs will cause serious damage to other normal organs.In this study,drug sustained-release microspheres were combined with bone tissue engineering scaffold materials,and a coaxial bone tissue engineering scaffold loaded with drug sustained-release microspheres was prepared by 3D printing technology,so that the system could achieve sustained and stable multistage sustained-release of antituberculosis drugs while maintaining certain mechanical properties.This study includes the following three parts:Firstly,under the conditions of different stirring speeds,different volume ratios of organic solvents to water phase and different solute ratios of GO solution to silk fibroin solution,According to the experimental results of scanning electron microscope,the best preparation parameters were obtained,drug loading,encapsulation rate and so on.Silk fibroin protein/streptomycin(SF/SM)and(GO/SF/SM)were prepared by using the optimal process,Among them,the drug loading of SF/SM drug-loaded microspheres was 6.596%,and the encapsulation rate was 52.19%.The drug loading of GO/SF/SM drug-loaded microspheres was 9.422%,and the encapsulation rate was60.51%.The cumulative release rate of the ball within 168 h is about 55.5% and 49.5%,After the modification of GO with SF,the drug loading and encapsulation rate of the microspheres were significantly improved.The slow and controlled release process of the two drug-loaded microspheres was both influenced by diffusion and dissolution.It conforms to the law of drug release of drug sustained-release microspheres.Secondly,graphene oxide/polyvinyl alcohol(GO/PVA)composite gel was used as binder to prepare uniaxial loading SM active agent,SF/SM microspheres and GO/SF/SM microspheres scaffold by 3D printing technology.The interaction between drug-loading microspheres and scaffold matrix material was characterized by infrared spectroscopy(FTIR).There was no chemical reaction between the microspheres and HA and PVA.The degradation,mechanics and sustained-release properties of the three kinds of uniaxial drug-loading/microspheres showed that GO/SF/SM microspheres could accelerate the degradation of the scaffolds and prolong the sustained-release of drugs.However,the mechanical properties of the uniaxial drug-loading SM microspheres were lower than those of the pure drug-loading SM scaffolds.The active protease had a certain effect on the comprehensive properties of the scaffold.Finally,coaxial core-loaded SM active agent,SF/SM microspheres and GO/SF/SM microspheres were prepared by 3D printing technology.It was determined that the addition of GO/SF/SM microspheres improved the degradation rate and mechanical properties of coaxial scaffolds,improved the drug burst release phenomenon of scaffolds and could release drugs stably in the long term.Compared with single coaxial scaffolds,it was found that the coaxial structure can realize gradient drug release and has certain mechanical properties. |
