Preparation And Drug Release Characteristics Of Tissue Engineered Bone Scaffolds Loaded With Rifampicin Graphene Oxide/Silk Fibroin Microspheres

Bone tuberculosis disease is a destructive disease caused by the invasion of bone or joint tissues by tuberculosis bacilli mainly spread by blood.Clinically,for the treatment of bone tuberculosis disease requiring "bone reconstruction",surgical removal of the lesion is generally used,followed by the filling of the defective bone tissue,and finally,the treatment means of placing or long-term oral anti-tuberculosis drugs in the lesion is adopted.The commonly used bone defect filling materials,such as autologous bone and allograft bone,only play a supporting role and cannot induce the reconstruction of new tissue.However,the method of placing anti-tuberculosis drugs on the lesions cannot guarantee the long-term effective concentration of the drugs,which requires multiple operations and drugs,increasing the pain of the patients.Oral administration is also difficult to ensure that the drug concentration reaches the focal area to meet the optimal bacteriostatic concentration,which will bring serious toxic and side effects to other normal organs in the long run.In order to solve the above problems,this study combined the microspheres with excellent performance with the materials of tissue engineering bone scaffolds,and prepared the microspheres and scaffolds with the properties of drug sustained release through 3D printing technology,so that the system could realize the continuous and stable release of anti-tb drugs while filling and repairing bone defects.This research includes the following three parts: first of all,to GO in,drug loading ratio,organic solvent as main factors such as proportion,set different levels,by single factor experiment combined with mixed levels orthogonal experiment,with electron microscope scanning,particle characterization,drug-loading rate,coating rate and related experimental results for judging basis,finally it is concluded that the drug highest category microsphere preparation process parameters,the group microspheres drug loadings was 12.3%,the coating rate of 65%,within a week of microspheres in drug cumulative release a quantity to around 80%,conform to the law of the sustained release microspheres of drug release;Next GO/PVA composite gel preparation of different concentration,and with the nanometer hydroxyapatite(nHA)with different proportion of compound,composite materials for different groups of stents,using electron microscope scanning,infrared spectrum(FTIR),X-ray diffraction(XRD)and mechanical properties test results,the ratio of different properties of the scaffolds were characterized,ultimately determine the n HA: 0.1% GO/PVA = 1 g: 1.5 ml,composite materials mechanical properties of the optimal and meet the safety requirements;Finally,according to the minimum bacteriostatic and bactericidal concentration of the anti-tb drug rifapin(RFP),the amount of microspheres,drugs and materials of the stent were calculated and determined based on the test results obtained in the first two parts.Then,the tissue engineering bone scaffold loaded with rifapin GO/SF microspheres was prepared by 3D printing technology.The degradation and sustained-release properties of scaffolds were evaluated by in vitro biodegradation and drug sustained-release experiments,which provided an effective experimental basis and support for the clinical application of such drug sustained-release systems.