Preparation Of Mechanically Enhanced Bioactive Glass-Reinforced 45S5 Bioglass Porous Scaffolds And Experimental Study On Their Osteogenic Capacity In Rabbit Bone Defects

Background:Massive bone defect resulted from various reasons is a challenging problem in the clinical practice.Lack of artificial biomaterials with the best effect is the core of the problem.45S5(?)bioactive glass is widely concerned due to its excellent bioactivity and bone binding ability,however,because of high brittleness and rapid degradation,45 S5(?)bioactive glass is only limited to the fixation of non-weight bearing bone.Poor mechanical properties,high brittleness and uncontrollable biodegradation is considered as the key problems in the bone regeneration in situ of porous bioactive glass.Thus,how to maintain the osteogenic capacity of bioactive glass and meanwhile to enhance its mechanical properties,and how to match the biodegradation rate with osteogenesis have been the urgent problems.Objective:The current study aimed to fabricate a mechanically reinforced 45S5 Bioglass(?)-derived glass cera1ic porous scaffolds by low-melt Zn/B-containing bioactive glass(BG-ZB)-assisted sintering at a low temperature.Relationships between BG-ZB content and the structural parameters,mechanical strength,and osteogenic capacity of the scaffolds were investigated systematically.In addition,the osteogenic activity and biological degradation were evaluated in rabbit bone defect model.Methods:1.The BG-ZB powders were added into the 45S5 Bioglass(?)powder/paraffin microsphere mixtures(paraffin diameter:350 or 500?m)and then compacted at 3 MPa in compression,and finally the green bodies were sintered at 900? to obtain porous scaffolds with highly bioactive BG-ZB of 0%,2%,or 4%of mass fraction(denoted as 45S5/ZB0-350,45S5/ZB2-350,45S5/ZB2-500,45S5/ZB4-350,45S5/ZB4-500).The as-sintered scaffolds were characterized by Hg instrument,mechanical test and X-Ray analysis.Furthermore,the degeneration performance was evaluated;2.The porous scaffolds of 45S5/ZB0-350,45S5/ZB4-350,45S5/ZB4-500 were respectively implanted in the critical-sized bone defect on distal femur of rabbits.The osteogenic capacity of the porous scaffolds was investigated by X-ray,MicroCT,histological and immunohistochemical analysis,at 6,12 and 18 weeks postoperatively.Results:1.The linear shrinkage rate of porous scaffolds in each group was less than 10%,with the open porosity of greater than 70%and the interconnected pore percentage of greater than 30%.However,the pore size and porosity of those glass ceramic scaffolds decreased slowly with the increase of BG-ZB content;2.The compressive strength of 45S5/ZB4-350 scaffolds was 19.4±1.2 Mpa,which was nearly 5-fold higher than that of the 45S5/ZnB0 scaffolds;3.The porous scaffolds in each group degraded gradually with the passage of time.However,the residual materials of 45S5/ZB4-500 was significantly less than that of other scaffolds at postoperative 18 weeks(P<0.001);4.The bone volume of newly formed bone in the 45S5/ZB4-500 scaffolds group was greater than that in other groups,at all the timepoints.At 18 weeks postoperatively,the bone volume fraction of 45S5/ZB4-500 scaffolds(58±1.9%)was significantly higher than that of the 45S5/ZB0-350 scaffolds(48±2.5%)(P=0.036);5.HE staining showed that more bone formation was observed in the 45S5/ZB4-500 scaffolds group,and that the bone volume fraction of 45S5/ZB4-500 scaffolds group(29.5 ± 3.7%)was higher than that of the other two groups(P<0.001),at the postoperative 18 weeks.Similarly,Masson trichrome staining showed that the rate of new bone formation in the 45S5/ZB4-500 scaffolds group was significantly higher than that in other groups;6.Immunohistochemistry results showed that the expression of Col-1 and OC in the 45S5/ZB4-500 scaffolds group was significantly higher than those in the other two groups at the 3 timepoints,respectively.Conclusions:The current study successfully fabricated a mechanically reinforced 45S5 Bioglass(?)-derived glass ceramic porous scaffolds by low-melt BG-ZB-assisted sintering at a low temperature condition.In particular,45S5/ZB4-500 scaffolds have both higher mechanical properties and better osteogenic capacities.This study resolves the problems that the 45S5 Bioglass(?)-derived glass ceramic porous scaffolds sintered at a low temperature develop poor mechanical properties,and that high temperature sintering decreases materials bioactivity.To summarize,the mechanically reinforced 45S5 Bioglass(?)-derived glass ceramic porous scaffolds could be potentially used for the regeneration and clinical repair of the bone defects.