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Engineered Regeneration 2024年第1期5卷 11-20页

作者： Selina Beal Iain Stewart Paul Hatton Marysia Placzek Ilida Ortega school of clinical dentistry and Insigneo Institute Claremont CrescentUniversity of SheffieldSheffield S102TAUK school of Biosciences University of SheffieldEnglandUK National Heart and Lung Institute Imperial CollegeLondon SW36LYUK

Tanycytes are stem/progenitor cells that reside in the hypothalamus of the adult vertebrate *** can be cultured as free-floating neurospheres in vitro but tend to spontaneously differentiate over *** we asked whether morphological cues provided by engineered polymer scaffolds can modify spontaneous ***-derived neurospheres were cultured on electrospun scaffolds,prepared with either random or aligned fiber *** dispersed widely on the scaffolds,and-on aligned scaffolds-were highly organized,orientated parallel to the *** analysis showed that cells cultured on aligned scaffolds showed significantly greater expression of the neural stem/progenitor cell marker,NrCAM and reduced expres-sion of differentiated cell markers in comparison to those cultured on random *** this shows that tanycytes respond to local engineered cues,and that a morphologically constrained environment can better main-tain tanycytes as stem *** aligned scaffold culture system provides a powerful tool to better investigate this novel stem/progenitor cell population.

关键词： Scaffold Tanycytes Neural stem/progenitor cells Fiber alignment Electrospinning

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead Department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich school of Medicine and dentistry Western UniversityLondonONCanada Deparment of clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration

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Regenerative Biomaterials 2024年第4期3卷 138-148页

作者： Woo-Jin Kim Jeong-Hyun Ryu Ji Won Kim Ki-Tae Kim Hye-Rim Shin Heein Yoon Hyun-Mo Ryoo Young-Dan Cho Department of Molecular Genetics School of Dentistry and Dental Research InstituteSeoul National UniversitySeoul03080Republic of Korea Department of Periodontology School of Dentistry and Dental Research InstituteSeoul National University and Seoul National University Dental HospitalSeoul03080Republic of Korea

clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and *** tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone *** encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore *** PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation *** PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in *** PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect *** findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.

关键词： 3D bioprinting bone-targeting lipoplex BMP2 bone regeneration

An overview of autophagy in the differentiation of dental stem cells

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BIOCELL 2024年第1期48卷 47-64页

作者： XITONG ZHAO TIANJUAN JU XINWEI LI CHANGFENG LIU LULU WANG LI-AN WU State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China

Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune *** properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative *** many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular *** evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress *** comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC *** achieve this goal,we dissect the intricacies of autophagy and its ***,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic ***,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic *** implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.

关键词： Dental stem cells Cell differentiation Autophagy Mitophagy Autophagy regulation

Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang Zhe Ma Haiyan Lu Hebei Key Laboratory of Stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Preventive dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in ***, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano Research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Center of Digital dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection

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Nano Research 2024年第3期17卷 1737-1747页

作者： Guiyan Wang Ning Yuan Jun Zhang Man Qin Suwei Dong Yuguang Wang Department of Pediatric dentistry Peking University School and Hospital of StomatologyBeijing 100081China State Key Laboratory of Natural and Biomimetic Drugs Chemical Biology Centerand School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical *** eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected ***,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is *** antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene *** this reaction,the acrylate gelatin undergoes cross-linkage within *** on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential *** results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial ***,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT *** a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization *** results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.

关键词： antimicrobial peptide vascular endothelial growth factor(VEGF)mimetic peptide sequential release visible-light crosslinking hydrogel wound therapy

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration

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Bone Research 2024年第2期12卷 361-371页

作者： Dandan Wang Yaru Guo Boon Chin Heng Xuehui Zhang Yan Wei Ying He Mingming Xu Bin Xia Xuliang Deng Department of Pediatric dentistry Peking University School and Hospital of StomatologyBeijing 100081P.R.China Department of Geriatric dentistry Peking University School and Hospital of StomatologyNational Center for StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081P.R.China Department of Dental Materials&Dental Medical Devices Testing Center Peking University School and Hospital of StomatologyNational Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081P.R.China

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 ***,we investigated the potential of alternative stem cell substitutes for facilitating bone *** this study,we successfully prepared cell membrane vesicles(CMVs)from BMSCs and *** results showed that BMSC-derived cell membrane vesicles(BMSC-CMVs)possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental ***-derived cell membrane vesicles(EC-CMVs)also contained BMP2 and VEGF derived from their parental ***-CMVs enhanced tube formation and migration ability of hUVECs,while EC-CMVs promoted the osteogenic differentiation of hBMSCs in *** a rat skull defect model,we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in ***,our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

关键词： hinder apparent vesicles

Glycerol solutions of highly concentrated biomineral counter-ions towards water-responsive mineralization: Demonstration on bacterial cellulose and its application in hard tissue repair

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Nano Research 2024年第3期17卷 2154-2163页

作者： Yunfei Zhao Xiaohao Liu Zhi Zhou Chaobo Feng Nan Luo Jiajun Yan Shuo Tan Yang Lu Feng Chen Bing-Qiang Lu Shisheng He Department of Orthopedic Spinal Pain Research InstituteShanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Preventive dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China

Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue *** current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low *** typically results in inefficient mineralization and weak control over biomineral ***,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic *** approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and *** resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy *** shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory *** study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.

关键词： biomineralization organic solvent bacterial cellulose(BC) hard tissue repair

3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

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Journal of Magnesium and Alloys 2024年第3期12卷 966-979页

作者： Xiao Zhao Siyi Wang Feilong Wang Yuan Zhu Ranli Gu Fan Yang Yongxiang Xu Dandan Xia Yunsong Liu Department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China National Center of Stomatology National Engineering Laboratory for Digital and Material Technology of StomatologyNational Clinical Research Center for Oral DiseasesBeijing Key Laboratory of Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing 100081China Department of Dental Materials Peking University School and Hospital of StomatologyBeijing 100081China

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its *** this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these *** used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling *** explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL *** 5 and 10 wt%Mg-1Ca/PCL composites were found to have good ***,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure *** vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and *** tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone *** results indicated that the Wnt/β-catenin pathway was involved in the osteogenic ***,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical *** of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone ***,there remain many limitations in the materials and manufacturing methods used to fabricate *** study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation ***,the fused deposition modeling method allows precise control of the macroscopic morphology and microsc

关键词： 3D printing Bone tissue engineering Magnesium Osteogenic Polycaprolactone Scaffold.