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
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
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
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
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.
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 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.
