Three-dimensional Printed Bioactive Glass Porous Scaffolds Treat A Large Bone Defect In A Rabbit Model

Background:Severe bone defect has always been one of the problems in orthopedics.Bone transplantation is an effective means to solve various bone defects.However,traditional bone transplantation methods often fail to meet clinical needs due to its limiting factors.Therefore,there is an urgent need for a bone substitute material with good biocompatibility and excellent osteogenic properties to be used in clinical practice.Objective:This research aims to construct a bioactive glass porous scaffold(BGS)through 3D printing technology,and to explore its internal microstructure and material properties.At the same time,it will be the first time to evaluate its in vivo osteogenic activity on a rabbit femoral shaft supercritical segmental bone defect model.Provide theoretical basis for clinical application.Methods:Bioactive glass microspheres were prepared by the organic template method,using polyvinyl alcohol(PVA)as a binder,and a cylindrical porous scaffold with a diameter of 0.5 cm,a height of 1.0 cm and 1.5 cm was printed by 3D fiber deposition technology.The mechanical properties,microscopic morphology and biocompatibility of the scaffolds were evaluated.A segmental bone defect model was made in the middle of the rabbit femoral shaft and divided into 1.0 cm defect group and 1.5 cm defect group,and then 3D BGS of the same length was implanted into the bone defect.Autogenous bone graft(ABG)was used as the positive control group,and the blank control group did not intervene.Mainly observe the effect of bone healing in the BGS group.The osteogenesis effect of 3D BGS was evaluated semi-quantitatively by X-ray images,histopathology and immunohistochemistry.Results:The stent has a three-dimensional perforated pore structure with a pore size of 800μm and a porosity of about 58.34%.The average compressive strength of the 1.0 cm and 1.5 cm stents are 24.47 Mpa and 23.15 Mpa,respectively.The apatite formed in vitro has good activity and can support cell adhesion and proliferation,which is in line with the basic properties of bioactive scaffolds.X-ray imaging showed that the BGS group could observe newly formed bone tissue around the scaffold 4 weeks after implantation,but different ossification enhancement trends were observed at different time points.The bone tissue formation in the 1.0 cm defect group was faster than that in the 1.0 cm defect group.1.5 cm defect group.Nevertheless,both groups eventually formed a callus connection at the defect at 18 weeks.In the ABG group,complete implant fusion eventually occurred,with no visible interface,and mature bone bridging the defect.The H&E staining and Masson staining of the BGS group showed that 3D BGS is easily degraded in the body to form a bone-like substance.With the gradual degradation of the bioglass,the newly ossified tissue grows from the edge of the material to the center of the material,and finally wraps the material.H&E staining and Masson staining of ABG group showed that new bone regeneration was active.The immunohistochemical analysis of the BGS group showed that in the 1.0 cm defect group,the expression levels of BMP2 and Col-Ⅰ protein reached their peak at the 8th week,and then gradually decreased at the 12th and 18th weeks,and the expression level of the RUNX2 protein It peaked from 8 weeks to 12 weeks,and decreased significantly at 18 weeks.In the 1.5 cm defect group,the expression levels of BMP2 and Col-I protein reached their peak at the 8th week,and then the two protein expression levels gradually decreased at the 12th and 18th weeks,but the protein expression level of RUNX2 was at the 12th week.It reached its peak and its expression decreased significantly at 18 weeks.Statistical results The expression level of BMP2 protein in the 1.0 cm defect group at 8 weeks was significantly different from the expression levels of BMP2 protein at 12 and 18 weeks(P<0.05);BMP2 protein and RUNX2 protein in the 1.0 cm defect group at 8 weeks Compared with the expression levels of BMP2 protein and RUNX2 protein in the 1.5 cm defect group at 8 weeks,there was a significant difference(P<0.05).There was no statistical difference in other indicators.Conclusions:The pBGS has large pore size and high porosity,and has excellent biomechanical properties.It has good apatite formation activity in vitro,can support cell adhesion and proliferation,and has good cell compatibility.All these results indicate that the 3D printed bioactive glass scaffold meets the basic properties of a bioactive scaffold.It has good biocompatibility,osteoconductivity and osteoinductivity in the repair of rabbit femoral critical segmental bone defect model,and the first attempt to repair the supercritical bone defect model shows that the biomaterial has certain osteogenesis Ability.In the case of limited amount and source of autologous bone,it is a large-scale animal model and clinical practice The reconstruction of large bone defects opened up a new way.