The functionalities and diverse metastable phases of multiferroic BiFeO_(3)(BFO)thin films depend on the misfit strain.Although mixed phase-induced strain relaxation in multiphase BFO thin films is well known,it is un...The functionalities and diverse metastable phases of multiferroic BiFeO_(3)(BFO)thin films depend on the misfit strain.Although mixed phase-induced strain relaxation in multiphase BFO thin films is well known,it is unclear whether a singlecrystalline BFO thin film can accommodate misfit strain without the involvement of its polymorphs.Thus,understanding the strain relaxation behavior is key to elucidating the lattice strain–property relationship.In this study,a correlative strain analysis based on dark-field inline electron holography(DIH)and quantitative scanning transmission electron microscopy(STEM)was performed to reveal the structural mechanism for strain accommodation of a single-crystalline BFO thin film.The nanoscale DIH strain analysis results indicated a random combination of multiple strain states that acted as a primary strain relief,forming irregularly strained nanodomains.The STEM-based bond length measurement of the corresponding strained nanodomains revealed a unique strain accommodation behavior achieved by a statistical combination of multiple modes of distorted structures on the unit-cell scale.The globally integrated strain for each nanodomain was estimated to be close to1.5%,irrespective of the nanoscale strain states,which was consistent with the fully strained BFO film on the SrTiO_(3) substrate.Density functional theory calculations suggested that strain accommodation by the combination of metastable phases was energetically favored compared to single-phase-mediated relaxation.This discovery allows a comprehensive understanding of strain accommodation behavior in ferroelectric oxide films,such as BFO,with various low-symmetry polymorphs.展开更多
It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enha...It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enhanced the secretion of MSC-derived exosomes with stronger anti-inflammatory protein,cytokine profiles,and functional RNA via altering COX2/PGE2 pathway.Recently,accumulating evidence has also revealed that biophysical cues(especially biomechanical cues)in cell microenvironment have significant effects not only on cells but also on their exosomes.It has been reported that applying bi-axial strain to MSCs induces formation of a stiffer cytoskeleton through mTORC2 signaling,which biases against adipogenic differentiation and toward osteoblastogenesis.At the same time,For example,dimensionality,composition and stiffness of the extracellular matrix(ECM)has been proved to affect the size and composition of exosomes secreted by cancer cells.However,the effects of biomechanical cues in the three-dimensional(3D)microenvironment on stem cell-derived exosomes remains to be unveiled.Therefore,it is important to understand the roles of 3D cell mechanical microenvironment in regulating the characteristics of stem cell-derived exosomes and develop more efficient approaches to enhance their functions.This study aimed to explore the changes in characteristics of exosomes secreted by MSCs in periodontium in response to the matrix strain in 3D.Periodontal ligament stem cells(PDLSCs)were cultured in a 3D strain microenvironment engineered with microscale magnetically stretched collagen hydrogels.The morphology,particle distribution,marker protein expression of PDLSC-derived exosomes were analyzed.Then the pro-osteogenic property of exosomes was evaluated by assessing cell viability,proliferation,migration and osteogenic differentiation of target cells,for instance human bone marrow mesenchymal stem cells(hBMSCs).Detailed characterizations revealed that PDLSC-derived exosomes in the 3D strain mi-croenvironment were with similar morphology,particle distribution and surface markers.Notably,Exosomes secreted by PDLSCs in strain microenvironment were more endocytosed by hBMSCs and were more potent in improving proliferation and migration of hBMSCs,comparing with PDLSCs in non-strain environment.Alizarin red staining and molecular biology experiments confirmed that treatment of exosomes secreted by PDLSCs under mechanical stimulation led to a significant increase in osteogenic differentiation of hBMSCs in vitro.Meanwhile,in vivo study also indicated that PDLSC-derived exosomes obtained from the 3D strain microenvironment could obviously promote new bone formation.Our findings revealed that mechanical cues profoundly affected the characteristics of PDLSC-derived exosomes,especially for their bio-activity,providing a foundation for using the 3D mechanical microenvironment to enhance the osteo-inductive functions of stem cell-derived exosomes in cell-free therapy for bone regeneration.展开更多
基金Samsung Research Fundings&Incubation Center of Samsung Electronics(Grant No.SRFCMA1702-01)Y.-M.K acknowledges partial support from the National Research Foundation of Korea(NRF)(Grant No.2023R1A2C2002403)funded by the Korean government in KoreaA.Borisevich acknowledges support from FaCT,an Energy Frontier Research Center funded by the U.S.Department of Energy,Office of Science,Office of Basic Energy Science,Collaboratives Research Division.
文摘The functionalities and diverse metastable phases of multiferroic BiFeO_(3)(BFO)thin films depend on the misfit strain.Although mixed phase-induced strain relaxation in multiphase BFO thin films is well known,it is unclear whether a singlecrystalline BFO thin film can accommodate misfit strain without the involvement of its polymorphs.Thus,understanding the strain relaxation behavior is key to elucidating the lattice strain–property relationship.In this study,a correlative strain analysis based on dark-field inline electron holography(DIH)and quantitative scanning transmission electron microscopy(STEM)was performed to reveal the structural mechanism for strain accommodation of a single-crystalline BFO thin film.The nanoscale DIH strain analysis results indicated a random combination of multiple strain states that acted as a primary strain relief,forming irregularly strained nanodomains.The STEM-based bond length measurement of the corresponding strained nanodomains revealed a unique strain accommodation behavior achieved by a statistical combination of multiple modes of distorted structures on the unit-cell scale.The globally integrated strain for each nanodomain was estimated to be close to1.5%,irrespective of the nanoscale strain states,which was consistent with the fully strained BFO film on the SrTiO_(3) substrate.Density functional theory calculations suggested that strain accommodation by the combination of metastable phases was energetically favored compared to single-phase-mediated relaxation.This discovery allows a comprehensive understanding of strain accommodation behavior in ferroelectric oxide films,such as BFO,with various low-symmetry polymorphs.
基金financially supported by the Young Elite Scientist Sponsorship Program by CAST ( 2018QNRC001)the China Postdoctoral Science Foundation ( 2018M631172)
文摘It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enhanced the secretion of MSC-derived exosomes with stronger anti-inflammatory protein,cytokine profiles,and functional RNA via altering COX2/PGE2 pathway.Recently,accumulating evidence has also revealed that biophysical cues(especially biomechanical cues)in cell microenvironment have significant effects not only on cells but also on their exosomes.It has been reported that applying bi-axial strain to MSCs induces formation of a stiffer cytoskeleton through mTORC2 signaling,which biases against adipogenic differentiation and toward osteoblastogenesis.At the same time,For example,dimensionality,composition and stiffness of the extracellular matrix(ECM)has been proved to affect the size and composition of exosomes secreted by cancer cells.However,the effects of biomechanical cues in the three-dimensional(3D)microenvironment on stem cell-derived exosomes remains to be unveiled.Therefore,it is important to understand the roles of 3D cell mechanical microenvironment in regulating the characteristics of stem cell-derived exosomes and develop more efficient approaches to enhance their functions.This study aimed to explore the changes in characteristics of exosomes secreted by MSCs in periodontium in response to the matrix strain in 3D.Periodontal ligament stem cells(PDLSCs)were cultured in a 3D strain microenvironment engineered with microscale magnetically stretched collagen hydrogels.The morphology,particle distribution,marker protein expression of PDLSC-derived exosomes were analyzed.Then the pro-osteogenic property of exosomes was evaluated by assessing cell viability,proliferation,migration and osteogenic differentiation of target cells,for instance human bone marrow mesenchymal stem cells(hBMSCs).Detailed characterizations revealed that PDLSC-derived exosomes in the 3D strain mi-croenvironment were with similar morphology,particle distribution and surface markers.Notably,Exosomes secreted by PDLSCs in strain microenvironment were more endocytosed by hBMSCs and were more potent in improving proliferation and migration of hBMSCs,comparing with PDLSCs in non-strain environment.Alizarin red staining and molecular biology experiments confirmed that treatment of exosomes secreted by PDLSCs under mechanical stimulation led to a significant increase in osteogenic differentiation of hBMSCs in vitro.Meanwhile,in vivo study also indicated that PDLSC-derived exosomes obtained from the 3D strain microenvironment could obviously promote new bone formation.Our findings revealed that mechanical cues profoundly affected the characteristics of PDLSC-derived exosomes,especially for their bio-activity,providing a foundation for using the 3D mechanical microenvironment to enhance the osteo-inductive functions of stem cell-derived exosomes in cell-free therapy for bone regeneration.
