Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controlla...Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical applications.The SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no gap.Moreover,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,respectively.In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway.The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells.Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and angiogenesis.Meanwhile,SMS hydrogel was proved to be antibacterial,especially for gram-negative bacteria.Furthermore,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone formation.Thus,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.展开更多
Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach.Injectable calcium phosphate bone cement(CPC)has attracted broad attention for its bioactivity...Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach.Injectable calcium phosphate bone cement(CPC)has attracted broad attention for its bioactivity,as compared to non-degradable polymethyl methacrylate cement.However,its brittleness,poor anti-washout property and uncontrollable biodegradability are the main challenges to limit its further clinical application mainly because of its stone-like dense structure and fragile inorganic-salt weakness.Herein,we developed a kind of injectable CPC bone cement with porous structure and improved robustness by incorporating poly(lactide-co-glycolic acid)(PLGA)nanofiber into CPC,with carboxymethyl cellulose(CMC)to offer good injectability as well as anti-wash-out capacity.Furthermore,the introduction of PLGA and CMC also enabled a formation of initial porous structure in the cements,where PLGA nanofiber endowed the cement with a dynamically controllable biodegradability which provided room for cell movement and bone ingrowth.Inter-estingly,the reinforced biodegradable cement afforded a sustainable provision of Ca^(2+)bioactive components,together with its porous structure,to improve synergistically new bone formation and osteo-integration in vivo by using a rat model of femur condyle defect.Further study on regenerative mechanisms indicated that the good minimally-invasive bone regeneration may come from the synergistic enhanced osteogenic effect of calcium ion enrichment and the improved revascularization capacity contributed from the porosity as well as the lactic acid released from PLGA nanofiber.These results indicate the injectable bone cement with high strength,anti-washout property and controllable biodegradability is a promising candidate for bone regeneration in a minimally-invasive approach.展开更多
Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivit...Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.展开更多
Objective: To evaluate the feasibility and effectiveness of a new approach for craniofacial augmentation by a minimally-invasive subpericranial injection. Three commercially available semi-liquid bioceramic bone-graft...Objective: To evaluate the feasibility and effectiveness of a new approach for craniofacial augmentation by a minimally-invasive subpericranial injection. Three commercially available semi-liquid bioceramic bone-grafting materials were examined for this application in a rat model. Material and Methods: Twenty-four adult male rats were randomly assigned to undergo onlay calvarial grafting by subpericranial injection of three semi-liquid bone void fillers: Norian SRS(calcium phosphate), ChronOs InjectTM (porous beta-tricalcium phosphate), or BonePlastharvested after 24 hours to serve as controls. The rest were studied after 16 weeks. The volume fraction of the following parameters was morphometrically measured: new bone, blood vessels, residual bone filler and inflammation. Results: In all study groups (including controls), histological examination demonstrated that bone fillers were successfully delivered to the desired subpericranial space by the percutaneous injection method. New bone formation was evidenced adjacent to the cranial bone in all the study groups. The Norian filler material survived in a significantly higher volume fraction (38.4% ± 6.5%) than the ChronOs filler (18.8% ± 1.6%;P 0.0001) and the BonePlast filler (17.8% ± 1.5%;P 0.0001). New bone was formed in all groups, particularly adjacent to the interface of graft material with native bone but only to minimal extent. Conclusion: This new approach for craniomaxillofacial augmentation was successfully demonstrated in a rat model. The Norian filler (calcium phosphate) demonstrated superior space preservation abilities. This model may be further applied to test new injectable bone substitutes in the craniomaxillofacial area.展开更多
目的 :评价注射型富血小板纤维蛋白(injectable-platelet rich fibrin,I-PRF)在上颌窦外提升术中促进成骨的效果。方法:选取2014年6月—2015年6月就诊于江苏省常州市口腔医院种植科,上颌后部磨牙或前磨牙单颗缺失可用骨高度3～5 mm,需...目的 :评价注射型富血小板纤维蛋白(injectable-platelet rich fibrin,I-PRF)在上颌窦外提升术中促进成骨的效果。方法:选取2014年6月—2015年6月就诊于江苏省常州市口腔医院种植科,上颌后部磨牙或前磨牙单颗缺失可用骨高度3～5 mm,需进行上颌窦外提升的患者46例,随机分为2组,A组窦底填塞Bio-oss骨粉,B组窦底填塞Bio-oss骨粉+I-PRF混合物。拍摄锥形束CT(CBCT),于术前测量剩余骨高度(residual bone height,RBH),术后即刻、术后6个月、术后12个月测量新生骨高度(new formed bone height,NFBH),并于术后4个月进行二期手术,术后6个月修复时测量ISQ值,比较2组成骨效果。采用SPSS 20.0软件包对数据进行统计学分析。结果:46例患者伤口均一期愈合,无感染、裂开等。CBCT检查显示,术前、术后12个月2组间RBH比较差异无统计学意义(P>0.05),术后即刻、术后6个月,A组RBH显著高于B组(P<0.05)。术后4个月,A组ISQ值显著高于B组(P<0.05),而术后6个月2组ISQ值无显著差异(P>0.05)。结论:I-PRF在上颌窦底外提升术中安全可靠,能够有效缩短愈合时间,增强成骨效果。展开更多
目的探讨应用可注射骨修复材料﹙Injectable Bone Regeneration Composite,IBRC﹚结合骨碎补总黄酮﹙As-semble Flavone Of Rhizome Drynaria,AFDR﹚修复大鼠极量颅骨缺损的效果。方法 40只雄性SD大鼠,制成颅骨极量骨缺损﹙Critical Siz...目的探讨应用可注射骨修复材料﹙Injectable Bone Regeneration Composite,IBRC﹚结合骨碎补总黄酮﹙As-semble Flavone Of Rhizome Drynaria,AFDR﹚修复大鼠极量颅骨缺损的效果。方法 40只雄性SD大鼠,制成颅骨极量骨缺损﹙Critical Size Defects,CSDs﹚模型,随机分为3组:A组IBRC修复大鼠颅骨缺损结合去离子水﹙DeionizedWater,DW﹚灌胃13只;B组IBRC修复大鼠颅骨缺损结合AFDR灌胃13只;C组IBRC复合重组人骨形成蛋白骨形成蛋白2﹙recombinanthumanBone Morphogenetic Protein 2,rhBMP2﹚修复大鼠颅骨缺损结合DW灌胃14只。术后2、4、6、8周各组随机处死2只大鼠取材做HE和Masson组织学观察,并于4、8、12周各组随机处死1只大鼠行Micro-CT扫描。结果单用IBRC修复极量骨缺损有作用,但骨痂生成慢;结合AFDR灌胃可以促进血管及纤维组织长入材料,促进成骨,但不及IBRC复合rhBMP2的修复速度及质量。结论 IBRC结合AFDR修复大鼠颅骨缺损可促进新骨形成,缩短骨缺损修复时间,虽然逊于IBRC复合rhBMP2的效果,但从安全、经济以及对骨质疏松的改善作用等方面考虑,有其进一步研究的价值。展开更多
Rapid maxillary expansion(RME),as a common treatment for craniomaxillofacial deformity,faces the challenge of high relapse rates and unsatisfactory therapeutic effects.In this study,a standardized Sprague-Dawley(SD)ra...Rapid maxillary expansion(RME),as a common treatment for craniomaxillofacial deformity,faces the challenge of high relapse rates and unsatisfactory therapeutic effects.In this study,a standardized Sprague-Dawley(SD)rat RME model was first established with a modified expander as well as retainer design and optimized anterior maxillary expanding force of 100 g which exerted the most synchronized mobility of mid-palatal suture and incisors.Via the standardized model,the high relapse rate was proven to be attributed to insufficient osteogenesis in expanded suture,requiring long-term retainer wearing in clinical situations.To reduce the relapse rate,mesoporous bioactive glass/fibrin glue(MBG/FG)composite hydrogels were developed for an in situ minimal invasive injection that enhance osteogenesis in the expanded palate.The component of 1 wt%MBG was adopted for enhanced mechanical strength,matched degradation rate and ion dissolution,excellent in vitro biocompatibility and osteoinductivity.Effects of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized model.The results demonstrated that injection of 1%MBG/FG composite hydrogel significantly promoted bone formation within the expanded mid-palatal suture,inhibited osteoclastogenesis and benefited the balance of bone remodeling towards osteogenesis.Combination of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after RME.The model establishment and the composite hydrogel development in this article might provide new insight to other craniomaxillofacial deformity treatment and design of bone-repairing biomaterials with higher regenerative efficiency.展开更多
There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capac...There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo.However,the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined.In this study,bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr(0 mol%to 12 mol%SrO)were created and evaluated in vitro and in vivo.The setting time of the cement increased with Sr substitution of the glass.Upon immersion in PBS,the cement degraded and converted more slowly to HA(hydroxyapatite)with increasing Sr substitution.The released Sr2+modulated the proliferation,differentiation,and mineralization of hBMSCs(human bone marrow mesenchymal stem cells)in vitro.Osteogenic characteristics were optimally enhanced with cement(designated BG6Sr)composed of particles substituted with 6mol%SrO.When implanted in rabbit femoral condyle defects,BG6Sr cement supported better peri-implant bone formation and bone-implant contact,comparing to cements substituted with 0mol%or 9mol%SrO.The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs.These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.展开更多
基金National Natural Science Foundation of China(Nos.82130027,82100963,82270953,81991505 and 81921002)Shanghai Rising-Star Program(21QA1405400)+1 种基金Natural Science Foundation of Shanghai(22ZR1436400)Innovative Research Team of High-Level Local Universities in Shanghai.
文摘Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical applications.The SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no gap.Moreover,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,respectively.In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway.The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells.Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and angiogenesis.Meanwhile,SMS hydrogel was proved to be antibacterial,especially for gram-negative bacteria.Furthermore,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone formation.Thus,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.
基金National Key R&D Program of China(2018YFE0201500)National Natural Science Foundation of China(81772317,82272457 and 51973060)+4 种基金National Natural Science Foundation of China for Innovative Research Groups(51621002)“Technology Innovation Action Plan”of Shanghai Science and Technology Commission(21S11902700)Natural Science Foundation of Shanghai(21ZR1412300)Shanghai Talent Development Fund(2020067)Shanghai“Rising Stars of Medical Talent”Youth Development Program(Youth Medical Talents–Specialist Program,[2020]087).
文摘Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach.Injectable calcium phosphate bone cement(CPC)has attracted broad attention for its bioactivity,as compared to non-degradable polymethyl methacrylate cement.However,its brittleness,poor anti-washout property and uncontrollable biodegradability are the main challenges to limit its further clinical application mainly because of its stone-like dense structure and fragile inorganic-salt weakness.Herein,we developed a kind of injectable CPC bone cement with porous structure and improved robustness by incorporating poly(lactide-co-glycolic acid)(PLGA)nanofiber into CPC,with carboxymethyl cellulose(CMC)to offer good injectability as well as anti-wash-out capacity.Furthermore,the introduction of PLGA and CMC also enabled a formation of initial porous structure in the cements,where PLGA nanofiber endowed the cement with a dynamically controllable biodegradability which provided room for cell movement and bone ingrowth.Inter-estingly,the reinforced biodegradable cement afforded a sustainable provision of Ca^(2+)bioactive components,together with its porous structure,to improve synergistically new bone formation and osteo-integration in vivo by using a rat model of femur condyle defect.Further study on regenerative mechanisms indicated that the good minimally-invasive bone regeneration may come from the synergistic enhanced osteogenic effect of calcium ion enrichment and the improved revascularization capacity contributed from the porosity as well as the lactic acid released from PLGA nanofiber.These results indicate the injectable bone cement with high strength,anti-washout property and controllable biodegradability is a promising candidate for bone regeneration in a minimally-invasive approach.
基金financial support from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 857287(BBCE).
文摘Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.
文摘Objective: To evaluate the feasibility and effectiveness of a new approach for craniofacial augmentation by a minimally-invasive subpericranial injection. Three commercially available semi-liquid bioceramic bone-grafting materials were examined for this application in a rat model. Material and Methods: Twenty-four adult male rats were randomly assigned to undergo onlay calvarial grafting by subpericranial injection of three semi-liquid bone void fillers: Norian SRS(calcium phosphate), ChronOs InjectTM (porous beta-tricalcium phosphate), or BonePlastharvested after 24 hours to serve as controls. The rest were studied after 16 weeks. The volume fraction of the following parameters was morphometrically measured: new bone, blood vessels, residual bone filler and inflammation. Results: In all study groups (including controls), histological examination demonstrated that bone fillers were successfully delivered to the desired subpericranial space by the percutaneous injection method. New bone formation was evidenced adjacent to the cranial bone in all the study groups. The Norian filler material survived in a significantly higher volume fraction (38.4% ± 6.5%) than the ChronOs filler (18.8% ± 1.6%;P 0.0001) and the BonePlast filler (17.8% ± 1.5%;P 0.0001). New bone was formed in all groups, particularly adjacent to the interface of graft material with native bone but only to minimal extent. Conclusion: This new approach for craniomaxillofacial augmentation was successfully demonstrated in a rat model. The Norian filler (calcium phosphate) demonstrated superior space preservation abilities. This model may be further applied to test new injectable bone substitutes in the craniomaxillofacial area.
文摘目的 :评价注射型富血小板纤维蛋白(injectable-platelet rich fibrin,I-PRF)在上颌窦外提升术中促进成骨的效果。方法:选取2014年6月—2015年6月就诊于江苏省常州市口腔医院种植科,上颌后部磨牙或前磨牙单颗缺失可用骨高度3～5 mm,需进行上颌窦外提升的患者46例,随机分为2组,A组窦底填塞Bio-oss骨粉,B组窦底填塞Bio-oss骨粉+I-PRF混合物。拍摄锥形束CT(CBCT),于术前测量剩余骨高度(residual bone height,RBH),术后即刻、术后6个月、术后12个月测量新生骨高度(new formed bone height,NFBH),并于术后4个月进行二期手术,术后6个月修复时测量ISQ值,比较2组成骨效果。采用SPSS 20.0软件包对数据进行统计学分析。结果:46例患者伤口均一期愈合,无感染、裂开等。CBCT检查显示,术前、术后12个月2组间RBH比较差异无统计学意义(P>0.05),术后即刻、术后6个月,A组RBH显著高于B组(P<0.05)。术后4个月,A组ISQ值显著高于B组(P<0.05),而术后6个月2组ISQ值无显著差异(P>0.05)。结论:I-PRF在上颌窦底外提升术中安全可靠,能够有效缩短愈合时间,增强成骨效果。
文摘目的探讨应用可注射骨修复材料﹙Injectable Bone Regeneration Composite,IBRC﹚结合骨碎补总黄酮﹙As-semble Flavone Of Rhizome Drynaria,AFDR﹚修复大鼠极量颅骨缺损的效果。方法 40只雄性SD大鼠,制成颅骨极量骨缺损﹙Critical Size Defects,CSDs﹚模型,随机分为3组:A组IBRC修复大鼠颅骨缺损结合去离子水﹙DeionizedWater,DW﹚灌胃13只;B组IBRC修复大鼠颅骨缺损结合AFDR灌胃13只;C组IBRC复合重组人骨形成蛋白骨形成蛋白2﹙recombinanthumanBone Morphogenetic Protein 2,rhBMP2﹚修复大鼠颅骨缺损结合DW灌胃14只。术后2、4、6、8周各组随机处死2只大鼠取材做HE和Masson组织学观察,并于4、8、12周各组随机处死1只大鼠行Micro-CT扫描。结果单用IBRC修复极量骨缺损有作用,但骨痂生成慢;结合AFDR灌胃可以促进血管及纤维组织长入材料,促进成骨,但不及IBRC复合rhBMP2的修复速度及质量。结论 IBRC结合AFDR修复大鼠颅骨缺损可促进新骨形成,缩短骨缺损修复时间,虽然逊于IBRC复合rhBMP2的效果,但从安全、经济以及对骨质疏松的改善作用等方面考虑,有其进一步研究的价值。
基金the National Natural Science Foundation of China(No.81970973,No.81771036,No.82071097,No.82071096)China Postdoctoral Science Foundation(2020T130422)Shanghai Sailing Program(19YF1425500,19YF1426500).
文摘Rapid maxillary expansion(RME),as a common treatment for craniomaxillofacial deformity,faces the challenge of high relapse rates and unsatisfactory therapeutic effects.In this study,a standardized Sprague-Dawley(SD)rat RME model was first established with a modified expander as well as retainer design and optimized anterior maxillary expanding force of 100 g which exerted the most synchronized mobility of mid-palatal suture and incisors.Via the standardized model,the high relapse rate was proven to be attributed to insufficient osteogenesis in expanded suture,requiring long-term retainer wearing in clinical situations.To reduce the relapse rate,mesoporous bioactive glass/fibrin glue(MBG/FG)composite hydrogels were developed for an in situ minimal invasive injection that enhance osteogenesis in the expanded palate.The component of 1 wt%MBG was adopted for enhanced mechanical strength,matched degradation rate and ion dissolution,excellent in vitro biocompatibility and osteoinductivity.Effects of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized model.The results demonstrated that injection of 1%MBG/FG composite hydrogel significantly promoted bone formation within the expanded mid-palatal suture,inhibited osteoclastogenesis and benefited the balance of bone remodeling towards osteogenesis.Combination of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after RME.The model establishment and the composite hydrogel development in this article might provide new insight to other craniomaxillofacial deformity treatment and design of bone-repairing biomaterials with higher regenerative efficiency.
基金supported by the National Key R&D Program of China(Grant No.2018YFC1106300 , 2017YFC1105000)the National Natural Science Foundation of China(Grant No.51802340,31870956,31771041 , 81672227)+6 种基金the Science and Technology Project of Guangdong Province-Doctoral startup fund of 2017(Grant No.2017A030310318)the Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)the Strategic Priority Research Program of CAS(Grant No.XDA16021000)the Shenzhen significant strategy layout project(Grant No.JCYJ20170413162104773)the Economic,Trade and information Commission of Shenzhen Municipality“Innovation and Industry Chain”(Grant No.20170502171625936)the Beijing Municipal Natural Science Foundation(Grant No.7161001)Beijing Municipal Commission of Health and Family Planning(Grant No.PXM2018_026275_000001).
文摘There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo.However,the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined.In this study,bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr(0 mol%to 12 mol%SrO)were created and evaluated in vitro and in vivo.The setting time of the cement increased with Sr substitution of the glass.Upon immersion in PBS,the cement degraded and converted more slowly to HA(hydroxyapatite)with increasing Sr substitution.The released Sr2+modulated the proliferation,differentiation,and mineralization of hBMSCs(human bone marrow mesenchymal stem cells)in vitro.Osteogenic characteristics were optimally enhanced with cement(designated BG6Sr)composed of particles substituted with 6mol%SrO.When implanted in rabbit femoral condyle defects,BG6Sr cement supported better peri-implant bone formation and bone-implant contact,comparing to cements substituted with 0mol%or 9mol%SrO.The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs.These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.
