| Bone tuberculosis is a common complication of extrapulmonary tuberculosis with high incidence,difficult to cure and easy to recurrence.The current treatment generally involves surgical removal of necrotic tissue at the lesion and long-term systemic administration.However,this method has problems such as long treatment cycle,high toxic side effects on liver,kidney,nerve and other tissues and organs,and low drug concentration at the defect lesion and lack of mechanical support carriers.Therefore,the preparation of a coaxial drug-loaded tissue engineering bone scaffold with good mechanical strength and drug slow release characteristics has important practical significance for the treatment of bone defects.This study will carry out experimental research in three aspects:screening the scaffold structure from the simulation results,optimizing the ratio of bone scaffold materials to improve the mechanical properties of the materials,exploring the influence of printing process on the molding quality,and analyzing the mechanics and slow-release characteristics of each group of drug-loaded bone scaffolds.Firstly,the scaffold structure with excellent mechanical strength and circulation is selected through the finite element simulation results to reduce the test period.Using UG to establish five porous bone scaffold models with of each structure;Using FLUENT to simulate the fluid flow in the porosity about 55%,and performing quasi-static compression simulation on the scaffold model through Workbench to judge the difference in mechanical properties the stent structure model,the flow velocity distribution and shear stress cloud graph data of different macrostructure characteristics are obtained to analyze the influence of the macropores and through holes of the stent structure on the fluidity of the fluid.It is concluded that the larger the structural pore area and the better the penetration,the worse the mechanical properties,but the more uniform the fluid flow rate in the stent and the smaller the shear stress,the better the biological flow performance.Secondly,optimizing the preparation parameter ratio of composite materials to improve the mechanical strength,and exploring the influence of process parameters on the molding of the scaffold to improve the molding quality.The composite of silk fibroin(SF),polyvinyl alcohol(PVA)and hydroxyapatite(HA)was selected as the scaffold material,and carring out the orthogonal experiment and analysis.When the ratio was combined as SF solution concentration 3%,PVA:SF(Mass ratio)=5:1,PVA/SF hydrogel:HA=1.6 m L:1 g,the material mechanical strength is the best.In the 3D printing process,when the rate ratio of the nozzle filament rate V2to the three-coordinate platform movement rate U is V2/U≈1.5,the ratio of the print layer height H to the nozzle diameter D is H/D≈0.8-1,the filament spacing L and the nozzle diameter the ratio of D is L/D≈1-2,the preparation process parameters are more compatible with the viscosity of the composite material,the molding effect is better,and the error is reduced in printing.Finally,the performance of four porous sustained-release drug-loaded bone scaffolds was analyzed and selecting drug-loaded scaffolds with good mechanics and drug release properties.The drug-loaded microspheres are prepared by the emulsification method,and the microspheres,in four ways the drug and the scaffold material are mixed as the slurry to 3D print the drug-loaded bone:porous uniaxial pure medicine,uniaxial microspheres,coaxial pure medicine,and coaxial microspheres bone scaffold.Performing microscopic morphology,compression experiment,in vitro degradation and drug release simulation experiments on each drug-loaded bone scaffold to compare the performance of the drug-loaded bone scaffold.The experiment shows that the porous coaxial bone scaffolds embedded with INH/RFP drug-loaded microspheres have good mechanical compressive properties,with a compressive strength of about 7.7MPa,and a compressive strength of3.7MPa after 12 weeks of degradation,which can reduce the"explosive release"of early-stage drugs.,INH has a cumulative drug release of 70%in 35 days,and RFP has a cumulative drug release of 40%in 84 days,which can achieve long-term stable and sustained drug release. |