Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes.The circadian clock mechanisms in brain and peripheral tissues can osc...Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes.The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli.Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown.Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms.Teeth enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during amelogenesis.This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis.Several physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and mineralization.Next,the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed.Circadian rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis imperfecta.Finally,future research trajectory in this field is extrapolated.It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.展开更多
Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells(BMSCs)and vascular endothelial cells(ECs).However,there are apparent limitations in stem cell-based therapy which hinder it...Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells(BMSCs)and vascular endothelial cells(ECs).However,there are apparent limitations in stem cell-based therapy which hinder its clinic translation.Hence,we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration.In this study,we successfully prepared cell membrane vesicles(CMVs)from BMSCs and ECs.The results showed that BMSC-derived cell membrane vesicles(BMSC-CMVs)possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells.EC-derived cell membrane vesicles(EC-CMVs)also contained BMP2 and VEGF derived from their parental cells.BMSC-CMVs enhanced tube formation and migration ability of hUVECs,while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro.Using a rat skull defect model,we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo.Therefore,our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.展开更多
Understanding the bioelectrical properties of bone tissue is key to developing new treatment strategies for bone diseases and injuries,as well as improving the design and fabrication of scaffold implants for bone tiss...Understanding the bioelectrical properties of bone tissue is key to developing new treatment strategies for bone diseases and injuries,as well as improving the design and fabrication of scaffold implants for bone tissue engineering.The bioelectrical properties of bone tissue can be attributed to the interaction of its various cell lineages(osteocyte,osteoblast and osteoclast)with the surrounding extracellular matrix,in the presence of various biomechanical stimuli arising from routine physical activities;and is best described as a combination and overlap of dielectric,piezoelectric,pyroelectric and ferroelectric properties,together with streaming potential and electro-osmosis.There is close interdependence and interaction of the various electroactive and electrosensitive components of bone tissue,including cell membrane potential,voltage-gated ion channels,intracellular signaling pathways,and cell surface receptors,together with various matrix components such as collagen,hydroxyapatite,proteoglycans and glycosaminoglycans.It is the remarkably complex web of interactive cross-talk between the organic and non-organic components of bone that define its electrophysiological properties,which in turn exerts a profound influence on its metabolism,homeostasis and regeneration in health and disease.This has spurred increasing interest in application of electroactive scaffolds in bone tissue engineering,to recapitulate the natural electrophysiological microenvironment of healthy bone tissue to facilitate bone defect repair.展开更多
External cervical resorption(ECR)refers to a pathological state in which resorption tissues penetrate into the dentin at the cervical aspect of the root.Despite being latent in its initial phase,ECR could cause severe...External cervical resorption(ECR)refers to a pathological state in which resorption tissues penetrate into the dentin at the cervical aspect of the root.Despite being latent in its initial phase,ECR could cause severe damage to mineralized dental tissue and even involve the pulp if not given timely diagnosis and treatment.Nevertheless,the etiology of ECR is still poorly understood,which adds to the difficulty in early diagnosis.ECR has received growing attention in recent years due to the increasing number of clinical cases.Several potential predisposing factors have been recognized in cross-sectional studies as well as case reports.In the meantime,studies on histopathology and pathogenesis have shed light on possible mechanisms of ECR.This review aims to summarize the latest findings in the pathogenesis and potential predisposing factors of ECR,so as to provide pragmatic reference for clinical practice.展开更多
1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many ...1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.展开更多
The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin,coupled with their ready accessibility and easy isolation from clinical waste,make these ideal cell source...The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin,coupled with their ready accessibility and easy isolation from clinical waste,make these ideal cell sources for neuroregeneration therapy.Nevertheless,these cells also have high propensity to differentiate into the osteo-odontogenic lineage.One strategy to enhance neurogenesis of these cells may be to recapitulate the natural physiological electrical microenvironment of neural tissues via electroactive or electroconductive tissue engineering scaffolds.Nevertheless,to date,there had been hardly any such studies on these cells.Most relevant scientific information comes from neurogenesis of other mesenchymal stem/stromal cell lineages(particularly bone marrow and adipose tissue)cultured on electroactive and electroconductive scaffolds,which will therefore be the focus of this review.Although there are larger number of similar studies on neural cell lines(i.e.PC12),neural stem/progenitor cells,and pluripotent stem cells,the scientific data from such studies are much less relevant and less translatable to dental and oral-derived stem cells,which are of the mesenchymal lineage.Much extrapolation work is needed to validate that electroactive and electroconductive scaffolds can indeed promote neurogenesis of dental and oral-derived stem cells,which would thus facilitate clinical applications in neuroregeneration therapy.展开更多
Y2O3-stabilized tetragonal zirconia polycrystalline （Y-TZP） ceramics with high-performance were prepared for dental ap- plication by use of the micro-emulsion and two-step sintering method. The crystal phase, morpho...Y2O3-stabilized tetragonal zirconia polycrystalline （Y-TZP） ceramics with high-performance were prepared for dental ap- plication by use of the micro-emulsion and two-step sintering method. The crystal phase, morphology, and microstructure of the reaction products were characterized by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, and transmission electron mi- croscopy （TEM）. XRD results show that the ceramics mainly consist of tetragonal zirconia. Physical and mechanical properties test results show that the bending strength, fracture toughness, and the density of full sintered Y-TZP ceramics are 1150 MPa, 5.53 MPa.m1/2, and 6.08 g/cm3, respectively, which suggest that the material is relatively suitable for dental restoration. The dental base crown machined with this material by CAD/CAM system exhibits a verisimilitude configuration and the material＇s expansion coefficient well matches that of the glaze. These results further indicate that the product can be used as a promising new ceramic material to fabricate dental base crowns and bridges.展开更多
Mesenchymal stem cell(MSC)migration determines the healing capacity of bone and is crucial in promoting bone regeneration.Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enz...Mesenchymal stem cell(MSC)migration determines the healing capacity of bone and is crucial in promoting bone regeneration.Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes.However,the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood.Here,this study shows that high-temperature requirement A3(HtrA3)overcomes the physical barrier and provides anchor points through collagen IV degradation,paving the way for MSC migration.HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing.HtrA3 degrades the surrounding collagen IV,which increases the collagen network porosity and increases integrinβ1 expression.Subsequently,integrinβ1 enhances the mechanotransduction of MSCs,thus remodeling the cytoskeleton,increasing cellular stiffness and nuclear translocation of YAP,eventually promoting the migration and subsequent osteogenic differentiation of MSCs.Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration.This study helps to reveal the novel roles of HtrA3,explore potential targets for regenerative medicine,and offer new insights for the development of bioactive materials.展开更多
Dentine hypersensitivity is an annoying worldwide disease,yet its mechanism remains unclear.The long-used hydrodynamic theory,a stimuli-induced fluid-flow process,describes the pain processes.However,no experimental e...Dentine hypersensitivity is an annoying worldwide disease,yet its mechanism remains unclear.The long-used hydrodynamic theory,a stimuli-induced fluid-flow process,describes the pain processes.However,no experimental evidence supports the statements.Here,we demonstrate that stimuli-induced directional cation transport,rather than fluid-flow,through dentinal tubules actually leads to dentine hypersensitivity.The in vitro/in vivo electro-chemical and electro-neurophysiological approaches reveal the cation current through the nanoconfined negatively charged dentinal tubules coming from external stimuli(pressure,pH,and temperature)on dentin surface and further triggering the nerve impulses causing the dentine hypersensitivity.Furthermore,the cationic-hydrogels blocked dentinal tubules could significantly reduce the stimuli-triggered nerve action potentials and the anionhydrogels counterpart enhances those,supporting the cation-flow transducing dentine hypersensitivity.Therefore,the inspired ion-blocking desensitizing therapies have achieved remarkable pain relief in clinical applications.The proposed mechanism would enrich the basic knowledge of dentistry and further foster breakthrough initiatives in hypersensitivity mitigation and cure.展开更多
Stem cells from human exfoliated deciduous teeth(SHED)uniquely exhibit high proliferative and neurogenic potential.Charged biomaterials have been demonstrated to promote neural differentiation of stem cells,but the do...Stem cells from human exfoliated deciduous teeth(SHED)uniquely exhibit high proliferative and neurogenic potential.Charged biomaterials have been demonstrated to promote neural differentiation of stem cells,but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated.Here,by utilizing different annealing temperatures prior to corona poling treatment,BaTiO_(3)/P(VDF-TrFE)ferroelectric nanocomposite membranes with varying charge polarization intensity(d_(33)≈0,4,12 and 19 pC N^(-1))were fabricated.Enhanced expression of neural markers,increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation.Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx,focal adhesion formation,FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge.Hence,this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.展开更多
Macrophage-mediated inflammation compromises bone repair in diabetic patients.Electrical signaling cues are known to regulate macrophage functions.However,the biological effects of electrical microenvironment from cha...Macrophage-mediated inflammation compromises bone repair in diabetic patients.Electrical signaling cues are known to regulate macrophage functions.However,the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated.Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite membrane.In vitro,the polarized BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite membranes inhibited high glucose-induced M1-type inflammation,by effecting changes in cell morphology,M1 marker expression and pro-inflammatory cytokine secretion in macrophages.This led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells(BM-MSCs).In vivo,the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory(M1)into the pro-healing(M2)phenotype,which in turn enhanced bone regeneration in rats with type 2 diabetes mellitus.Mechanistic studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway,thereby inducing favorable osteo-immunomodulatory effects.Our study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions,and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.展开更多
Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell ...Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.展开更多
Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures.However,how mechanical characteristics of extracellular ...Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures.However,how mechanical characteristics of extracellular matrix(ECM)modulates tip cell formation has been largely neglected.In this study,we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues.Stiffened matrix promoted sprouting from endothelial cell(EC)spheroids and upregulated expressions of tip cell-enriched genes in vitro.Moreover,tip cells showed increased cellular stiffness,more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs.We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state.YAP is subsequently activated and translocated into nucleus,leading to increased tip cell specification.p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification.Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis,shedding light on the role of mechanotransduction in tip cell formation.This is of special significance in biomaterial design and treatment of some pathological situations.展开更多
BaTiO3 nanofibers of about 400 nm in diameter were synthesized via electrospinning.The evolution of the morphology and phase composition of the BaTiO3 nanofibers was studied by scanning electron microscopy and X-ray d...BaTiO3 nanofibers of about 400 nm in diameter were synthesized via electrospinning.The evolution of the morphology and phase composition of the BaTiO3 nanofibers was studied by scanning electron microscopy and X-ray diffraction within the annealing temperature of 750-1050 ℃.Higher annealing temperature led to rougher surface and better crystallization of the BaTiO3 nanofibers.Below 1050 ℃,the BaTiO3 nanofibers maintained its large aspect ratios and could still be regarded as individual nanofiber.The dielectric permittivities of the BaTiO3 nanofibers（εr 820） were calculated with the MG equation by considering the porous bulk specimens as composites of BaTiO3 nanofibers and air.The ferroelectric properties of the BaTiO3nanofibers were measured by using a ferroelectric analyzer coupled with an atomic force microscope.P-E loop measured for the BaTiO3 nanofiber exhibits small hysteresis.展开更多
Myoclonus dystonia syndrome(MDS)is an inherited movement disorder,and most MDS-related mutations have so far been found in theε-sarcoglycan(SGCE)coding gene.By generating SGCE-knockout(KO)and human 237 C>T mutatio...Myoclonus dystonia syndrome(MDS)is an inherited movement disorder,and most MDS-related mutations have so far been found in theε-sarcoglycan(SGCE)coding gene.By generating SGCE-knockout(KO)and human 237 C>T mutation knock-in(KI)mice,we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients.SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro.Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology.Indeed,using a zebrafish MDS model,we found that among 1700 screened chemical compounds,Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models.Our study strengthens the notion that mutations of SGCE lead to MDS and most likely,SGCE functions to brake synaptogenesis in the CNS.展开更多
In the past few decades,we have seen the rapid development of bioactive materials which can repair damaged tissues and save human lives.Traditionally,researchers have sought to develop bioactive materials with unique ...In the past few decades,we have seen the rapid development of bioactive materials which can repair damaged tissues and save human lives.Traditionally,researchers have sought to develop bioactive materials with unique physical and chemical properties,such as stiffness,functional groups,nanotopographies and stimulus-responsive properties,to promote tissue regeneration at the biointerface.展开更多
基金supported by grants from the National Key R&D Program of China(2022YFC2401803)the National Natural Science Foundation of China(51973004)+1 种基金the China Postdoctoral Science Foundation(2023M730116)the Peking University Medicine Sailing Program for YoungScholars’Scientific&Technological Innovation(BMU2023YFJHPY012).
文摘Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes.The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli.Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown.Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms.Teeth enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during amelogenesis.This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis.Several physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and mineralization.Next,the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed.Circadian rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis imperfecta.Finally,future research trajectory in this field is extrapolated.It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.
基金supported by the National Natural Science Foundation of China(Nos.U22A20160,82221003,81991505,82201123)China Postdoctoral Science Foundation(2022M720290,2021M700279)Hubei Provincial Key Laboratory of Oral and Maxillofacial Development and Regeneration Open Fund(2022kqhm004).
文摘Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells(BMSCs)and vascular endothelial cells(ECs).However,there are apparent limitations in stem cell-based therapy which hinder its clinic translation.Hence,we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration.In this study,we successfully prepared cell membrane vesicles(CMVs)from BMSCs and ECs.The results showed that BMSC-derived cell membrane vesicles(BMSC-CMVs)possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells.EC-derived cell membrane vesicles(EC-CMVs)also contained BMP2 and VEGF derived from their parental cells.BMSC-CMVs enhanced tube formation and migration ability of hUVECs,while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro.Using a rat skull defect model,we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo.Therefore,our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.
基金the National Key Research and Development Program of China,Grant/Award Number:2021YFB3800800 and 2021YFC2400400National Natural Science Foundation of China,Grant/Award Number:82022016,51973004,81991505 and 52103312+2 种基金the Beijing Municipal Natural Science Foundation,Grant/Award Number:7222226National Program for Multidisciplinary Cooperative Treatment on Major Diseases,Grant/Award Number:PKUSSNMP-202002Peking University School of Stomatology National Clinical Key Discipline Construction Project,Grant/Award Number:PKUSSNKP-T202101。
文摘Understanding the bioelectrical properties of bone tissue is key to developing new treatment strategies for bone diseases and injuries,as well as improving the design and fabrication of scaffold implants for bone tissue engineering.The bioelectrical properties of bone tissue can be attributed to the interaction of its various cell lineages(osteocyte,osteoblast and osteoclast)with the surrounding extracellular matrix,in the presence of various biomechanical stimuli arising from routine physical activities;and is best described as a combination and overlap of dielectric,piezoelectric,pyroelectric and ferroelectric properties,together with streaming potential and electro-osmosis.There is close interdependence and interaction of the various electroactive and electrosensitive components of bone tissue,including cell membrane potential,voltage-gated ion channels,intracellular signaling pathways,and cell surface receptors,together with various matrix components such as collagen,hydroxyapatite,proteoglycans and glycosaminoglycans.It is the remarkably complex web of interactive cross-talk between the organic and non-organic components of bone that define its electrophysiological properties,which in turn exerts a profound influence on its metabolism,homeostasis and regeneration in health and disease.This has spurred increasing interest in application of electroactive scaffolds in bone tissue engineering,to recapitulate the natural electrophysiological microenvironment of healthy bone tissue to facilitate bone defect repair.
基金the Beijing Municipal Natural Science Foundation(grant number:7182185).
文摘External cervical resorption(ECR)refers to a pathological state in which resorption tissues penetrate into the dentin at the cervical aspect of the root.Despite being latent in its initial phase,ECR could cause severe damage to mineralized dental tissue and even involve the pulp if not given timely diagnosis and treatment.Nevertheless,the etiology of ECR is still poorly understood,which adds to the difficulty in early diagnosis.ECR has received growing attention in recent years due to the increasing number of clinical cases.Several potential predisposing factors have been recognized in cross-sectional studies as well as case reports.In the meantime,studies on histopathology and pathogenesis have shed light on possible mechanisms of ECR.This review aims to summarize the latest findings in the pathogenesis and potential predisposing factors of ECR,so as to provide pragmatic reference for clinical practice.
文摘1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.
基金supported by the National Natural Science Foundation of China(Nos.82022016,51772006,51973004,and 81991505)Peking University Medicine Fund(Nos.PKU2020LCXQ009 and BMU2020PYB029)。
文摘The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin,coupled with their ready accessibility and easy isolation from clinical waste,make these ideal cell sources for neuroregeneration therapy.Nevertheless,these cells also have high propensity to differentiate into the osteo-odontogenic lineage.One strategy to enhance neurogenesis of these cells may be to recapitulate the natural physiological electrical microenvironment of neural tissues via electroactive or electroconductive tissue engineering scaffolds.Nevertheless,to date,there had been hardly any such studies on these cells.Most relevant scientific information comes from neurogenesis of other mesenchymal stem/stromal cell lineages(particularly bone marrow and adipose tissue)cultured on electroactive and electroconductive scaffolds,which will therefore be the focus of this review.Although there are larger number of similar studies on neural cell lines(i.e.PC12),neural stem/progenitor cells,and pluripotent stem cells,the scientific data from such studies are much less relevant and less translatable to dental and oral-derived stem cells,which are of the mesenchymal lineage.Much extrapolation work is needed to validate that electroactive and electroconductive scaffolds can indeed promote neurogenesis of dental and oral-derived stem cells,which would thus facilitate clinical applications in neuroregeneration therapy.
文摘Y2O3-stabilized tetragonal zirconia polycrystalline （Y-TZP） ceramics with high-performance were prepared for dental ap- plication by use of the micro-emulsion and two-step sintering method. The crystal phase, morphology, and microstructure of the reaction products were characterized by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, and transmission electron mi- croscopy （TEM）. XRD results show that the ceramics mainly consist of tetragonal zirconia. Physical and mechanical properties test results show that the bending strength, fracture toughness, and the density of full sintered Y-TZP ceramics are 1150 MPa, 5.53 MPa.m1/2, and 6.08 g/cm3, respectively, which suggest that the material is relatively suitable for dental restoration. The dental base crown machined with this material by CAD/CAM system exhibits a verisimilitude configuration and the material＇s expansion coefficient well matches that of the glaze. These results further indicate that the product can be used as a promising new ceramic material to fabricate dental base crowns and bridges.
基金supported by the National Natural Science Foundation of China 81991505,U22A20160,82221003,82201123,82022016,and 52273258the National Key Research and Development Program of China 2021YFB3800800+1 种基金the Beijing Municipal Natural Science Foundation 7222226China Postdoctoral Science Foundation 2021M700279 and 2023T160029.We thank Dr.Siying Qin at the National Center for Protein Sciences of Peking University for technical help with AFM.
文摘Mesenchymal stem cell(MSC)migration determines the healing capacity of bone and is crucial in promoting bone regeneration.Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes.However,the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood.Here,this study shows that high-temperature requirement A3(HtrA3)overcomes the physical barrier and provides anchor points through collagen IV degradation,paving the way for MSC migration.HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing.HtrA3 degrades the surrounding collagen IV,which increases the collagen network porosity and increases integrinβ1 expression.Subsequently,integrinβ1 enhances the mechanotransduction of MSCs,thus remodeling the cytoskeleton,increasing cellular stiffness and nuclear translocation of YAP,eventually promoting the migration and subsequent osteogenic differentiation of MSCs.Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration.This study helps to reveal the novel roles of HtrA3,explore potential targets for regenerative medicine,and offer new insights for the development of bioactive materials.
基金We thank the National Key R&D Program of China(No.2020YFA0710401)the National Natural Science Foundation of China(Nos.82225012,81922019,82071161,81991505,22122207,21988102,and 52075138)+1 种基金the Young Elite Scientist Sponsorship Program by CAST(No.2020QNRC001)the Beijing Nova Program(No.211100002121013).
文摘Dentine hypersensitivity is an annoying worldwide disease,yet its mechanism remains unclear.The long-used hydrodynamic theory,a stimuli-induced fluid-flow process,describes the pain processes.However,no experimental evidence supports the statements.Here,we demonstrate that stimuli-induced directional cation transport,rather than fluid-flow,through dentinal tubules actually leads to dentine hypersensitivity.The in vitro/in vivo electro-chemical and electro-neurophysiological approaches reveal the cation current through the nanoconfined negatively charged dentinal tubules coming from external stimuli(pressure,pH,and temperature)on dentin surface and further triggering the nerve impulses causing the dentine hypersensitivity.Furthermore,the cationic-hydrogels blocked dentinal tubules could significantly reduce the stimuli-triggered nerve action potentials and the anionhydrogels counterpart enhances those,supporting the cation-flow transducing dentine hypersensitivity.Therefore,the inspired ion-blocking desensitizing therapies have achieved remarkable pain relief in clinical applications.The proposed mechanism would enrich the basic knowledge of dentistry and further foster breakthrough initiatives in hypersensitivity mitigation and cure.
基金supported by the National Key Research and Development Program of China(2021YFB3800800,2021YFC2400400)the National Natural Science Foundation of China(Nos.82022016,81991505,51973004,52103312)+1 种基金the Beijing Municipal Natural Science Foundation(7222226)Peking University Medicine Fund(PKU2020LCXQ009).
文摘Stem cells from human exfoliated deciduous teeth(SHED)uniquely exhibit high proliferative and neurogenic potential.Charged biomaterials have been demonstrated to promote neural differentiation of stem cells,but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated.Here,by utilizing different annealing temperatures prior to corona poling treatment,BaTiO_(3)/P(VDF-TrFE)ferroelectric nanocomposite membranes with varying charge polarization intensity(d_(33)≈0,4,12 and 19 pC N^(-1))were fabricated.Enhanced expression of neural markers,increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation.Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx,focal adhesion formation,FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge.Hence,this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.
基金This work was supported by the National Key R&D Program of China(2018YFC1105303/04)National Natural Science Foundation of China(Nos.51772006,31670993,51973004,81991505,82022016)+3 种基金Beijing Municipal Science&Technology Commission Projects(Z181100002018001)Peking University Medicine Fund(Nos.PKU2020LCXQ009,BMU2020PYB029)Natural Science Foundation of Hunan Province(2019JJ50779)Health and Family Planning Commission of Hunan Province(20180246).
文摘Macrophage-mediated inflammation compromises bone repair in diabetic patients.Electrical signaling cues are known to regulate macrophage functions.However,the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated.Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite membrane.In vitro,the polarized BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite membranes inhibited high glucose-induced M1-type inflammation,by effecting changes in cell morphology,M1 marker expression and pro-inflammatory cytokine secretion in macrophages.This led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells(BM-MSCs).In vivo,the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory(M1)into the pro-healing(M2)phenotype,which in turn enhanced bone regeneration in rats with type 2 diabetes mellitus.Mechanistic studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway,thereby inducing favorable osteo-immunomodulatory effects.Our study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions,and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.
基金supported by the National Key R&D Program of China(2020YFA0710401)National Natural Science Foundation of China(51972005,51903003,51973226,81871782 and 51672009)the Youth Innovation Promotion Association CAS(No.2019031)for financial support.
文摘Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.
基金This work was supported by the National Key R&D Program of China(2018YFC1105303/04)National Natural Science Foundation of China(Nos.81991505,82022016,51772006,31670993,51973004)+1 种基金Beijing Municipal Science&Technology Commission Projects(Z181100002018001)We thank Dr.Siying Qin at the National Center for Protein Sciences of Peking University for technical help with AFM.
文摘Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures.However,how mechanical characteristics of extracellular matrix(ECM)modulates tip cell formation has been largely neglected.In this study,we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues.Stiffened matrix promoted sprouting from endothelial cell(EC)spheroids and upregulated expressions of tip cell-enriched genes in vitro.Moreover,tip cells showed increased cellular stiffness,more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs.We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state.YAP is subsequently activated and translocated into nucleus,leading to increased tip cell specification.p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification.Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis,shedding light on the role of mechanotransduction in tip cell formation.This is of special significance in biomaterial design and treatment of some pathological situations.
基金financial supports from the National Basic Research Program of China(No.2012CB933900)the Key Technologies R&D Program of China(No.2012BAI07B00)+3 种基金the National High Technology Research and Development Program of China(No.2011AA030100)the Foundation for the Authors of National Excellent Doctoral Dissertations of China(Grant No. 201144)Beiing Nova Program(Grant No.XX2013037)Tsinghua University(Grant No.20121087925)
文摘BaTiO3 nanofibers of about 400 nm in diameter were synthesized via electrospinning.The evolution of the morphology and phase composition of the BaTiO3 nanofibers was studied by scanning electron microscopy and X-ray diffraction within the annealing temperature of 750-1050 ℃.Higher annealing temperature led to rougher surface and better crystallization of the BaTiO3 nanofibers.Below 1050 ℃,the BaTiO3 nanofibers maintained its large aspect ratios and could still be regarded as individual nanofiber.The dielectric permittivities of the BaTiO3 nanofibers（εr 820） were calculated with the MG equation by considering the porous bulk specimens as composites of BaTiO3 nanofibers and air.The ferroelectric properties of the BaTiO3nanofibers were measured by using a ferroelectric analyzer coupled with an atomic force microscope.P-E loop measured for the BaTiO3 nanofiber exhibits small hysteresis.
基金supported by National Natural Science Foundation of China(31630028,91632305,and 91632303)the Fund for Distinguished Young Scholars of National Natural Science Foundation of China(81425009 and 81425007)+1 种基金the National Basic Science Research Program of China(2012CB933900 and 2015CB755600)the Strategic Priority Research Program(B)of China(XDB02050500)。
文摘Myoclonus dystonia syndrome(MDS)is an inherited movement disorder,and most MDS-related mutations have so far been found in theε-sarcoglycan(SGCE)coding gene.By generating SGCE-knockout(KO)and human 237 C>T mutation knock-in(KI)mice,we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients.SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro.Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology.Indeed,using a zebrafish MDS model,we found that among 1700 screened chemical compounds,Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models.Our study strengthens the notion that mutations of SGCE lead to MDS and most likely,SGCE functions to brake synaptogenesis in the CNS.
基金supported by the National Natural Science Foundation of China(51932002,52072127,51773045,21772030,51922032,and 21961160720)the National Natural Science Foundation of China(51773045,21772030,51922032,and 21961160720)for financial support+2 种基金the National Key Research and Development Program of China(2017YFA0206600)the National Key Research and Development Program of China(2017YFA0206600)the Science and Technology Program of Guangzhou(202002030308)。
文摘In the past few decades,we have seen the rapid development of bioactive materials which can repair damaged tissues and save human lives.Traditionally,researchers have sought to develop bioactive materials with unique physical and chemical properties,such as stiffness,functional groups,nanotopographies and stimulus-responsive properties,to promote tissue regeneration at the biointerface.
