Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of uniq...Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multidisciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.展开更多
Epithelial–mesenchymal transition(EMT)is involved in both physiological and pathological processes.EMT plays an essential role in the invasion,migration and metastasis of tumours.Autophagy has been shown to regulate ...Epithelial–mesenchymal transition(EMT)is involved in both physiological and pathological processes.EMT plays an essential role in the invasion,migration and metastasis of tumours.Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma(HNSCC).Herein,we investigated whether autophagy also regulates EMT in HNSCC.Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1(FN1)correlated with poorer prognosis and higher tumour pathological grade in HNSCC.Data from SCC-25 cells demonstrated that rapamycin and Earle’s balanced salt solution(EBSS)promoted autophagy,leading to increased FN1 degradation,while 3-methyladenine(3-MA),bafilomycin A1(Baf A1)and chloroquine(CQ)inhibited autophagy,leading to decreased FN1 degradation.On the other hand,autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells,and rapamycin did not promote autophagy in Cal-27 cells;also in addition,FN1 degradation was inhibited.Further,we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132.Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy–lysosome pathway of FN1 degradation.Finally,data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines.These results indicate that autophagy significantly promotes the degradation of FN1.Collectively,our findings clearly suggest that FN1,as a marker of EMT,has adverse effects on HNSCC and elucidate the autophagy–lysosome degradation mechanism of FN1.展开更多
Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immun...Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.展开更多
Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of ...Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area,we evaluated the hollow polydopamine nanoparticles(HPDA NPs),in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect.Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility.Results of qRT-PCR,ALP,and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells(rBMSCs)in vitro.Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo,especially tacrolimus.These results suggest that the HPDA NPs,the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability,have good prospect to treat the bone defect in future clinical practice.展开更多
The endoplasmic reticulum(ER)is the main site for regulating protein synthesis and processing.Endoplasmic reticulum stress plays a role in regulating the osteogenic differentiation of stem cells and general osteoblast...The endoplasmic reticulum(ER)is the main site for regulating protein synthesis and processing.Endoplasmic reticulum stress plays a role in regulating the osteogenic differentiation of stem cells and general osteoblasts.Bone marrow stromal cells(BMSCs,also known as bone marrow mesenchymal stem cells)are a group of progenitor cells that contain a small number of bone stem cells(SSCs)that rebuild cartilage,bone,stroma,and fat cells that support hematopoiesis and bone marrow.Therefore,due to their self-renewal and differentiation capabilities,they have become an important resource for researching regenerative medicine and tissue engineering treatment strategies.Exposure of osteoblasts to physical and biochemical stimuli facilitates rapid activation of early tissue repair processes in organisms.Therefore,the rational regulation of the induction conditions of osteoblasts has become a hot research topic.This article reviews the recent advances in the role of endoplasmic reticulum stress in the process of osteoblast differentiation.展开更多
Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic ...Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and diseases.EVs can be traced to their cells of origin and exhibit a similar function.Moreover,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent cells.Mesenchymal stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell therapy.The mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously noted.However,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell therapy.Especially EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample collection.Here,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular communication.Furthermore,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases.We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation.We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.展开更多
Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limite...Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limited outcomes in the repair and regeneration of bone defects that might be attributed to the reciprocal interventions of these pathways. In order to satisfy the combinational and sequential activation of BMP and WNT pathways, inspired by the heterogeneous hydrogel-liked structures of Brasenia, heterogeneous alginate/chitosan hydrogels were fabricated and spatially loaded with FK506 and BIO to achieve sustained and sequential release of the activators. Alkaline phosphatase staining, alizarin red staining and q RT-PCR results suggested that FK506 and BIO enhanced osteoblastic differentiation in vitro when used separately. Besides, by mixing and matching the activators and the hydrogel layers, a superior releasing mode that a combination of early FK506 release and following BIO release was identified via both in vitro and in vivo explorations for most efficient bone regeneration. These results suggested that drug-loaded heterogeneous hydrogels possess great potentials in treating bone loss defects for future clinical practice.展开更多
For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ...For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.展开更多
The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degrad...The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting ability.Encapsulating or binding these biologics within biomaterials is an effective way to address these problems.Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and versatility.However,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune response.Here,we summarize how key physical and chemical properties of hydrogels affect the immune response.We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials.Then,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical cues.Thus,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.展开更多
The effect of Pt and Cu electrodes on the resistive switching properties and failure behaviors of amorphous ZrO_2 ?lms were investigated. Compared with Cu/ZrO_2/Pt structures, the Pt/ZrO_2/Pt structures exhibit better...The effect of Pt and Cu electrodes on the resistive switching properties and failure behaviors of amorphous ZrO_2 ?lms were investigated. Compared with Cu/ZrO_2/Pt structures, the Pt/ZrO_2/Pt structures exhibit better resistive switching properties such as the higher resistance ratio of OFF/ON states, the longer switching cycles and narrow distribution of OFF state resistance(Roff). The switching mechanism in the Pt/ZrO_2/Pt structure can be attributed to the formation and rupture of oxygen vacancy ?laments; while in the Cu/Zr O2/Pt structure, there exist both oxygen vacancy ?laments and Cu ?laments. The formation of Cu?laments is related to the redox reaction of Cu electrode under the applied voltage. The inhomogeneous dispersive injection of Cu ions results in the dispersive Roff and signi?cant decrease of operate voltage.Schematic diagrams of the formation of conductive ?laments and the failure mechanism in the Cu/ZrO_2/Pt structures are also proposed.展开更多
基金project was supported by grants from National Natural Science Foundations of China (Nos. 82025010, 81630023, 81900917)Changjiang Scholars and Innovative Research Team (No. IRT13082)+4 种基金CAMS Innovation Fund for Medical Sciences (No. 2019-I2M-5-022)Beijing Municipal Science and Technology Commision (Nos. Z181100001618002, Z211100002921057)Capital’s Funds for Health Improvement and Research (No.CFH2022-1-1091)Beijing Municipal Administration of Hospitals’ Mission Project (No. SML20150203)Beijing Municipal Administration of Hospitals’ Dengfeng Project (No. DFL20190202)。
文摘Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multidisciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
基金This work was supported by grants from the National Natural Science Foundation of China(881320108011,81600823,81920108012,81870741)China Postdoctoral Science Foundation(2017M611332,2019M661177)+2 种基金Provincial Science Foundation of Jilin Provincial Department of Finance(JLS22019378-28)Bethune Project of Jilin University(2018A06,2015340)Jilin Scientific and Technological Development Programme(20170101093JC).
文摘Epithelial–mesenchymal transition(EMT)is involved in both physiological and pathological processes.EMT plays an essential role in the invasion,migration and metastasis of tumours.Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma(HNSCC).Herein,we investigated whether autophagy also regulates EMT in HNSCC.Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1(FN1)correlated with poorer prognosis and higher tumour pathological grade in HNSCC.Data from SCC-25 cells demonstrated that rapamycin and Earle’s balanced salt solution(EBSS)promoted autophagy,leading to increased FN1 degradation,while 3-methyladenine(3-MA),bafilomycin A1(Baf A1)and chloroquine(CQ)inhibited autophagy,leading to decreased FN1 degradation.On the other hand,autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells,and rapamycin did not promote autophagy in Cal-27 cells;also in addition,FN1 degradation was inhibited.Further,we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132.Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy–lysosome pathway of FN1 degradation.Finally,data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines.These results indicate that autophagy significantly promotes the degradation of FN1.Collectively,our findings clearly suggest that FN1,as a marker of EMT,has adverse effects on HNSCC and elucidate the autophagy–lysosome degradation mechanism of FN1.
基金supported by grants from the National Key R&D Program of China (2016YFC1102800)National Natural Science Foundation of China (81879741, 51872332)+1 种基金Natural Science Foundation of Liaoning Province (20170541040)China Postdoctoral Science Foundation Grant (2020M681020)
文摘Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
基金supported by grants from the National Key Research and Development Program of China(2016YFC1102800)the Natural Science Foundation of China(81870741,21774045,and 81920108012)Program for JLU Science and Technology Innovative Research Team(2017TD-11)。
文摘Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area,we evaluated the hollow polydopamine nanoparticles(HPDA NPs),in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect.Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility.Results of qRT-PCR,ALP,and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells(rBMSCs)in vitro.Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo,especially tacrolimus.These results suggest that the HPDA NPs,the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability,have good prospect to treat the bone defect in future clinical practice.
基金Supported by the National Natural Science Foundation of China(No.81870741)。
文摘The endoplasmic reticulum(ER)is the main site for regulating protein synthesis and processing.Endoplasmic reticulum stress plays a role in regulating the osteogenic differentiation of stem cells and general osteoblasts.Bone marrow stromal cells(BMSCs,also known as bone marrow mesenchymal stem cells)are a group of progenitor cells that contain a small number of bone stem cells(SSCs)that rebuild cartilage,bone,stroma,and fat cells that support hematopoiesis and bone marrow.Therefore,due to their self-renewal and differentiation capabilities,they have become an important resource for researching regenerative medicine and tissue engineering treatment strategies.Exposure of osteoblasts to physical and biochemical stimuli facilitates rapid activation of early tissue repair processes in organisms.Therefore,the rational regulation of the induction conditions of osteoblasts has become a hot research topic.This article reviews the recent advances in the role of endoplasmic reticulum stress in the process of osteoblast differentiation.
基金supported by the National Key R&D Program of China(No.2022YFC2504200)the National Natural Science Foundation of China(No.82270960)the Science&Technology Development Talent Project of Jilin Financial Department,Jilin,China(No.JCSZ2021893-35)to AZ.
文摘Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and diseases.EVs can be traced to their cells of origin and exhibit a similar function.Moreover,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent cells.Mesenchymal stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell therapy.The mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously noted.However,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell therapy.Especially EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample collection.Here,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular communication.Furthermore,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases.We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation.We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.
基金supported by the National Natural Science Foundation of China (Nos. 81970903 and 81920108012)Fundamental Research Funds for the Central Universities,Jilin Provincial Science & Technology Department (No. 20200201527JC)+1 种基金Jilin Department of Health (No. 2019Q013)Department of Finance of Jilin Province (No. JCSZ2019378-6)。
文摘Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limited outcomes in the repair and regeneration of bone defects that might be attributed to the reciprocal interventions of these pathways. In order to satisfy the combinational and sequential activation of BMP and WNT pathways, inspired by the heterogeneous hydrogel-liked structures of Brasenia, heterogeneous alginate/chitosan hydrogels were fabricated and spatially loaded with FK506 and BIO to achieve sustained and sequential release of the activators. Alkaline phosphatase staining, alizarin red staining and q RT-PCR results suggested that FK506 and BIO enhanced osteoblastic differentiation in vitro when used separately. Besides, by mixing and matching the activators and the hydrogel layers, a superior releasing mode that a combination of early FK506 release and following BIO release was identified via both in vitro and in vivo explorations for most efficient bone regeneration. These results suggested that drug-loaded heterogeneous hydrogels possess great potentials in treating bone loss defects for future clinical practice.
基金This work was supported by the National Natural Science Foundation of China （Nos. 51503085, 51373061 and 21304090）, Science Foundation of China University of Petroleum, Beijing （No. 2462017YJRC027）, open project of state key laboratory of supramolecular structure and materials （No. sklssm201724） and Graduate Innovation Fund of Jilin University （Project 2016112）.
基金supported by the National Nature Science Foundation of China(Nos.51861145311,22005338)Science Foundation of China University of Petroleum,Beijing(No.2462017YJRC027)Open Project of State Key Laboratory of Superhard Materials(Jilin University 201802)。
文摘For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.
基金supported by the ERC Proof-of-Concept Grant(MINGRAFT),the AO Foundation Grant(AOCMF-17-19M)the Medical Research Council(UK Regenerative Medicine Platform Acellular/Smart Materials-3D Architecture,MR/R015651/1)+2 种基金the National Natural Science Foundation of China(81870741,82001023),China Postdoctoral Science Foundation(2019M661177)Natural Science Foundation of Liaoning Province(2020-MS-154)China Scholarship Council([2020]50).
文摘The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting ability.Encapsulating or binding these biologics within biomaterials is an effective way to address these problems.Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and versatility.However,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune response.Here,we summarize how key physical and chemical properties of hydrogels affect the immune response.We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials.Then,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical cues.Thus,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.
基金supported by the National Natural Science Foundation of China(Nos.51202107 and 50932001)the Opening Funding of National Laboratory of Solid State Microstructure(No.M26017)+1 种基金the Doctoral Scientific Research Foundation of Henan Normal University(No.5101029170260)the support of PAPD in Jiangsu Province and Doctoral Fund of Ministry of Education of the People’s Republic of China(No.20120091110049)
文摘The effect of Pt and Cu electrodes on the resistive switching properties and failure behaviors of amorphous ZrO_2 ?lms were investigated. Compared with Cu/ZrO_2/Pt structures, the Pt/ZrO_2/Pt structures exhibit better resistive switching properties such as the higher resistance ratio of OFF/ON states, the longer switching cycles and narrow distribution of OFF state resistance(Roff). The switching mechanism in the Pt/ZrO_2/Pt structure can be attributed to the formation and rupture of oxygen vacancy ?laments; while in the Cu/Zr O2/Pt structure, there exist both oxygen vacancy ?laments and Cu ?laments. The formation of Cu?laments is related to the redox reaction of Cu electrode under the applied voltage. The inhomogeneous dispersive injection of Cu ions results in the dispersive Roff and signi?cant decrease of operate voltage.Schematic diagrams of the formation of conductive ?laments and the failure mechanism in the Cu/ZrO_2/Pt structures are also proposed.
