Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effectivetherapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promisingstrat...Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effectivetherapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promisingstrategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study,motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized anexosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of thebenefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhanceosteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated thebeneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bonemarrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells(HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells,stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and acceleratedbone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed thatPLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, weprovide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesisproperty.展开更多
目的评价浓缩生长因子(concentrated growth factor,CGF)应用于上颌前牙区唇侧骨缺损引导骨再生(guided bone regeneration,GBR)的效果。方法选取上颌前牙区单牙缺失伴唇侧水平向骨缺损40例,随机分为观察组和对照组各20例。观察组使用...目的评价浓缩生长因子(concentrated growth factor,CGF)应用于上颌前牙区唇侧骨缺损引导骨再生(guided bone regeneration,GBR)的效果。方法选取上颌前牙区单牙缺失伴唇侧水平向骨缺损40例,随机分为观察组和对照组各20例。观察组使用浓缩生长因子+骨粉+胶原膜行引导骨再生术;对照组使用骨粉+胶原膜行常规引导骨再生术。术后行软组织愈合评估,术后半年评价骨增量的效果。结果观察组软组织伤口一期愈合率为100%,对照组为75%,观察组高于对照组,差异具有统计学意义(P=0.017)。观察组术后半年骨宽度增加量为(3.70±0.28)mm,对照组为(2.96±0.16)mm,观察组骨增量大于对照组,差异具有统计学意义(P=0.000)。结论 CGF能促进上颌前牙区骨缺损引导骨再生术的成骨量。展开更多
Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect...Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region.Three-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair.Here,we used modified bioinks comprising gelatin,gelatin methacryloyl(GelMA),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds.Moreover,MSNs sustainably released BMP-4 for long-term effectiveness.In 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors.BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds.Furthermore,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment.And 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone repair.In conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.展开更多
Background We previously showed that nano-hydroxyapatite/carboxymethyl chitosan （n-Ha/CMCS） displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicit...Background We previously showed that nano-hydroxyapatite/carboxymethyl chitosan （n-Ha/CMCS） displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicity. The aim of this study was to determine the effect of the same composite with vascular endothelial growth factor （VEGF）transfected bone marrow stromal cells （BMSCs） in a rabbit radial defect model.展开更多
基金Natural science Foundation of Liaoning Province,China,grant number of 2020-ZLLH-40.
文摘Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effectivetherapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promisingstrategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study,motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized anexosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of thebenefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhanceosteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated thebeneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bonemarrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells(HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells,stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and acceleratedbone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed thatPLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, weprovide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesisproperty.
基金supported by National Key R&D Program of China(2018YFB1105600/2018YFC2002300/2018YFA0703000)National Natural Science Foundation of China(81772326/81702124/81902195)+3 种基金Fundamental research program funding of Ninth People's Hospital affiliated to Shanghai JiaoTong University School of Medicine(JYZZ070)Project of Shanghai Science and Technology Commission(18441903700/19XD1434200/18431903700/19441908700/19441917500)Translational Medicine Innovation Project of Shanghai Jiao Tong University School of Medicine(TM201613/TM201915)Project of Shanghai Jiading National Health and Family Planning Commission(KYXM 2018-KY-03).
文摘Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region.Three-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair.Here,we used modified bioinks comprising gelatin,gelatin methacryloyl(GelMA),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds.Moreover,MSNs sustainably released BMP-4 for long-term effectiveness.In 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors.BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds.Furthermore,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment.And 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone repair.In conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.
文摘Background We previously showed that nano-hydroxyapatite/carboxymethyl chitosan （n-Ha/CMCS） displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicity. The aim of this study was to determine the effect of the same composite with vascular endothelial growth factor （VEGF）transfected bone marrow stromal cells （BMSCs） in a rabbit radial defect model.
文摘目的探讨应用IIizarov外固定架骨搬运技术治疗胫骨骨折术后感染、骨缺损临床疗效。方法对60例胫骨骨折术后感染、骨缺损患者依据Ilizarov技术标准进行治疗。术后定期摄X线片复查,评估牵张成骨情况。结果 60例均获得随访,时间18~30个月。骨搬运完成时间2~7个月,骨搬运长度6~18 cm。患者未出现血管神经损伤等并发症。6例出现钉道反应,1例切口皮缘水肿,均经治疗后愈合;17例搬运后期出现对线不良,经调整骨搬运方向、少量植骨,均获对位对线骨性愈合。骨搬运完成后9个月,按Paley et al骨折愈合评分标准评价疗效:优45例,良6例,可8例,差1例。骨缺损断端骨愈合及牵张成骨区成骨愈合满意,软组织创面愈合满意,所有患肢长度恢复良好,与健侧对比无明显差异。结论采用Ilizarov外固定架骨搬运技术进行感染扩创、炎性病变切除、骨段搬运修复骨缺损,对胫骨术后感染的控制、肢体功能的重建具有确切的临床疗效。
