The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most...The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most of them are macromolecular proteins with the drawbacks of short effective half-life,poor stability and high cost,which constrain their clinical translation.Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule,dimethyloxalylglycine(DMOG),and an osteoinductive inorganic nanomaterial,nanosilicate(nSi)into poly(lactic-co-glycolic acid)(PLGA)fibers by electrospinning.The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized.Thereafter,the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells(PDLSCs)in vitro.Additionally,the fibrous membranes were transplanted into rat periodontal defects,and tissue regeneration was assessed with histological evaluation,micro-computed tomography(micro-CT),and immunohistochemical analysis.DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility.PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers,higher alkaline phosphatase(ALP)activity,and more tube formation in comparison with single application.Further,in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34stromal cells,induced angiogenesis and osteogenesis,and regenerated cementum-ligament-bone complex in periodontal defects.Consequently,the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration.DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis,and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.展开更多
Critical oral-maxillofacial bone defects,damaged by trauma and tumors,not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct.Personalized biomaterials ...Critical oral-maxillofacial bone defects,damaged by trauma and tumors,not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct.Personalized biomaterials customized by 3D printing technology have the potential to match oralmaxillofacial bone repair and regeneration requirements.Laponite(LAP)nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity.Herein,porous nanosilicate-functionalized polycaprolactone(PCL/LAP)was fabricated by 3D printing technology,and its bioactivities in bone regeneration were investigated in vitro and in vivo.In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the viability of bone marrow mesenchymal stem cells(BMSCs).PCL/LAP functioned to stimulate osteogenic differentiation of BMSCs at the mRNA and protein levels and elevated angiogenic gene expression and cytokine secretion.Moreover,BMSCs cultured on PCL/LAP promoted the angiogenesis potential of endothelial cells by angiogenic cytokine secretion.Then,PCL/LAP scaffolds were implanted into the calvarial defect model.Toxicological safety of PCL/LAP was confirmed,and significant enhancement of vascularized bone formation was observed.Taken together,3D-printed PCL/LAP scaffolds with brilliant osteogenesis to enhance bone regeneration could be envisaged as an outstanding bone substitute for a promising change in oral-maxillofacial bone defect reconstruction.展开更多
基金the National Natural Science Foundation of China(No.81670993,81873716,and 81901009)The Construction Engineering Special Fund of“Taishan Scholars”of Shandong Province(No.ts20190975 and tsqn201909180)+1 种基金National Key R&D Program of China(No.2017YFB0405400)Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong,The National Key Research and Development Program of China(No.2017YFA0104604),Open Foundation of Shandong Provincial Key Laboratory of Oral Tissue Regeneration(No.SDKQ201901,SDKQ201904).The funders had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.The authors also thank Prof.Hongyu Zhang and Dr.Yi Wang from Tsinghua University for technical guidance.The authors declare that no financial or other potential competing interests exist with regard to this study.
文摘The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most of them are macromolecular proteins with the drawbacks of short effective half-life,poor stability and high cost,which constrain their clinical translation.Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule,dimethyloxalylglycine(DMOG),and an osteoinductive inorganic nanomaterial,nanosilicate(nSi)into poly(lactic-co-glycolic acid)(PLGA)fibers by electrospinning.The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized.Thereafter,the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells(PDLSCs)in vitro.Additionally,the fibrous membranes were transplanted into rat periodontal defects,and tissue regeneration was assessed with histological evaluation,micro-computed tomography(micro-CT),and immunohistochemical analysis.DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility.PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers,higher alkaline phosphatase(ALP)activity,and more tube formation in comparison with single application.Further,in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34stromal cells,induced angiogenesis and osteogenesis,and regenerated cementum-ligament-bone complex in periodontal defects.Consequently,the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration.DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis,and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.
基金supported by the National Natural Science Foundation of China(Grant No.81870766)the Fujian Medical Innovation Project,Fujian Province(2020CXA048)+1 种基金the Fujian Medical Talents Training Project(2020GGA061)the Startup Fund for scientific research,Fujian Medical University(Grant No.2019QH2041).
文摘Critical oral-maxillofacial bone defects,damaged by trauma and tumors,not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct.Personalized biomaterials customized by 3D printing technology have the potential to match oralmaxillofacial bone repair and regeneration requirements.Laponite(LAP)nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity.Herein,porous nanosilicate-functionalized polycaprolactone(PCL/LAP)was fabricated by 3D printing technology,and its bioactivities in bone regeneration were investigated in vitro and in vivo.In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the viability of bone marrow mesenchymal stem cells(BMSCs).PCL/LAP functioned to stimulate osteogenic differentiation of BMSCs at the mRNA and protein levels and elevated angiogenic gene expression and cytokine secretion.Moreover,BMSCs cultured on PCL/LAP promoted the angiogenesis potential of endothelial cells by angiogenic cytokine secretion.Then,PCL/LAP scaffolds were implanted into the calvarial defect model.Toxicological safety of PCL/LAP was confirmed,and significant enhancement of vascularized bone formation was observed.Taken together,3D-printed PCL/LAP scaffolds with brilliant osteogenesis to enhance bone regeneration could be envisaged as an outstanding bone substitute for a promising change in oral-maxillofacial bone defect reconstruction.
