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Enamel biomimetics—fiction or future of dentistry?

International Journal of Oral Science 2019年第1期11卷 1-9页

作者： Mirali Pandya Thomas G.H.Diekwisch center for craniofacial research and Diagnosis Texas A&M College of Dentistry

Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering,(i) enamel synthesis using physico-chemical means,(ii) protein matrix-guided enamel crystal growth,(iii) enamel surface remineralization,(iv) cell-based enamel engineering, and(v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal *** methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogeninderived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.

关键词： complex mineralized Biochemical methods

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Multispecies communities:interspecies interactions influence growth on saliva as sole nutritional source

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International Journal of Oral Science 2011年第2期3卷 49-54页

作者： Paul E.Kolenbrander National Institute of Dental and craniofacial research National Institutes of Health

Human oral bacteria live in multispecies communities in the biofilm called dental plaque. This review focuses on the interactions of seven species and the ability of each species individually and together with other species to grow on saliva as the sole source of nutrient. Community formation in biofihns in flow cells is monitored using species-specific fluorophore-conjugated immunoglobulin Gy and images are captured by confocal microscopy. Early colonizing veillonellae emerge from this review of interspecies interactions in saliva as a critical genus that guides the development of multispecies communities. Highly selective interspecies recognition is evident as initial colonizers pair with early and middle colonizers to form multispecies communities that grow on saliva.

关键词： growth on saliva multispecies communities biofilm flow cell interspecies interactions

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Optogenetics in oral and craniofacial research

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 656-671页

作者： Qinmeng ZHANG Luyao SONG Mengdie FU Jin HE Guoli YANG Zhiwei JIANG Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310000China Zhejiang University School of Medicine Hangzhou 310058China

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high *** modified photosensory sensors are engineered into proteins to modulate conformational changes with light ***,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral ***,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial *** addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational *** the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental *** future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.

关键词： Lasers Cell differentiation Bacterial virulence Nervous system Neurophysiology Behavioral science

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Salivary Gland Branching Morphogenesis——Recent Progress and Future Opportunities

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International Journal of Oral Science 2010年第3期2卷 117-126页

作者： Jeff Chi-feng Hsu Kenneth M.Yamada Laboratory of Cell and Developmental Biology National Institute of Dental and Craniofacial ResearchNational Institutes of Health

Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality-of-life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branchingmorphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell-cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process.

关键词： salivary gland epithelium branching morpho-genesis fibronectin E-cadherin growth factor

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The recent advances in scaffolds for integrated periodontal regeneration

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Bioactive Materials 2021年第10期6卷 3328-3342页

作者： Hyun Nyun Woo Young Joon Cho Solaiman Tarafder Chang H.Lee center for Dental and craniofacial research Columbia University Medical Center630 W.168 St.VC12-212New YorkNY10032USA

The periodontium is an integrated,functional unit of multiple tissues surrounding and supporting the tooth,including but not limited to cementum(CM),periodontal ligament(PDL)and alveolar bone(AB).Periodontal tissues can be destructed by chronic periodontal disease,which can lead to tooth *** support of the treatment for periodontally diseased tooth,various biomaterials have been applied starting as a contact inhibition membrane in the guided tissue regeneration(GTR)that is the current gold standard in dental ***,various biomaterials have been prepared in a form of tissue engineering scaffold to facilitate the regeneration of damaged periodontal *** a physical substrate to support healing of a single type of periodontal tissue to multi-phase/bioactive scaffold system to guide an integrated regeneration of periodontium,technologies for scaffold fabrication have emerged in last *** review covers the recent advancements in development of scaffolds designed for periodontal tissue regeneration and their efficacy tested in vitro and in *** and Cons of different biomaterials and design parameters implemented for periodontal tissue regeneration are also discussed,including future perspectives.

关键词： Periodontium Periodontitis Bioactive scaffold Multi-phase scaffold Periodontal regeneration

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Chronic inflammation deteriorates structure and function of collagen fibril in rat temporomandibular joint disc

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International Journal of Oral Science 2019年第1期11卷 42-49页

作者： Shengjie Cui Yu Fu Yan Liu Xiaoxing Kou Jieni Zhang Yehua Gan Yanheng Zhou Xuedong Wang Department of Orthodontics Peking University School and Hospital of Stomatology center for craniofacial Stem Cell research and Regeneration Peking University School and Hospital of Stomatology center for Temporomandibular Disorders and Orofacial Pain Peking University School and Hospital of Stomatology

Collagen is the building component of temporomandibular joint(TMJ) discs and is often affected by inflammation in temporomandibular disorders. The macromechanical properties of collagen are deteriorated by chronic inflammation. However,the mechanism by which inflammation influences disc function remains unknown. The relationship between the ultrastructure and nanomechanical properties of collagen in inflamed discs should be clarified. Seven-week-old female Sprague–Dawley rats were randomly divided into two groups. Chronic TMJ inflammation was induced by intra-articular injection of complete Freund's adjuvant, and samples were harvested after 5 weeks. Picrosirius staining revealed multiple colours under polarized light, which represented alternative collagen bundles in inflamed discs. Using atomic force microscopy scanning, the magnitude of Young's modulus was reduced significantly accompanied with disordered collagen fibril arrangement with porous architecture of inflamed discs. Transmission electron microscopy scanning revealed a non-uniform distribution of collagen fibres, and oversized collagen fibrils were observed in inflamed discs. Fourier transform infrared microspectroscopy revealed a decrease in 1 338 cm^(-1)/amide II area ratio of collagen in different regions. The peak positions of amide I and amide II bands were altered in inflamed discs,indicating collagen unfolding. Our results suggest that sustained inflammation deteriorates collagen structures, resulting in the deterioration of the ultrastructure and nanomechanical properties of rat TMJ discs.

关键词： temporomandibular joint(TMJ female Sprague-Dawley

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Platelet-rich plasma enhances adipose-derived stem cell-mediated angiogenesis in a mouse ischemic hindlimb model

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World Journal of Stem Cells 2018年第12期10卷 212-227页

作者： Chia-Fang Chen Han-Tsung Liao Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital craniofacial research center Chang Gung Memorial Hospital College of Medicine Chang Gung University

AIM To evaluate the angiogenic effect of platelet-rich plasma(PRP)-preconditioned adipose-derived stem cells(ADSCs) both in vitro and in a mouse ischemic hindlimb *** ADSCs were divided based on culture medium: 2.5% PRP, 5% PRP, 7.5% PRP, and 10% PRP. Cell proliferation rate was analyzed using the MTS assay. The gene expression of CD31, vascular endothelial growth factor, hypoxia-inducible factors, and endothelial cell nitric oxide synthase was analyzed using reverse transcription polymerase chain reaction. Cell markers and structural changes were assessed through immunofluorescence staining and the tube formation assay. Subsequently, we studied the in vivo angiogenic capabilities of ADSCs by a mouse ischemic hindlimb *** The proliferation rate of ADSCs was higher in the 2.5%, 5%, and 7.5% PRP groups. The expression of hypoxia-inducible factor, CD31, vascular endothelial growth factor, and endothelial cell nitric oxide synthase in the 5% and 7.5% PRP groups increased. The 5%, 7.5%, and 10% PRP groups showed higher abilities to promote both CD31 and vascular endothelial growth factor production and tubular structure formation in ADSCs. According to laser Doppler perfusion scan, the perfusion ratios of ischemic limb to normal limb were significantly higher in 5% PRP, 7.5% PRP, and human umbilical vein endothelial cells groups compared with the negative control and fetal bovine serum(FBS) groups(0.88 ± 0.08, 0.85 ± 0.07 and 0.81 ± 0.06 for 5%, 7.5% PRP and human umbilical vein endothelial cells compared with 0.42 ± 0.17 and 0.54 ± 0.14 for the negative control and FBS, P < 0.01).CONCLUSION PRP-preconditioned ADSCs presented endothelial cell characteristics in vitro and significantly improved neovascularization in ischemic hindlimbs. The optimal angiogenic effect occurred in 5% PRP-and 7.5% PRPpreconditioned ADSCs.

关键词： Platelet-rich plasma Adipose-derived stem cells Mesenchymal stem cell Angiogenesis Endothelial differentiation Mouse ischemic hindlimb model

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The importance of a potential phosphorylation site in enamelin on enamel formation

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International Journal of Oral Science 2017年第4期9卷 210-215页

作者： Wen-Juan Yan Pan Ma Ye Tian Jing-Ya Wang Chun-Lin Qin Jian Q Feng Xiao-Fang Wang Department of Biomedical Sciences and center for craniofacial research and Diagnosis Texas A&M University College of DentistryDallasUSA Department of Endodontics Nanfang HospitalSouthern Medical UniversityGuangzhouChina

Enamelin （ENAM） has three putative phosphoserines （pSers） phosphorylated by a Golgi-associated secretory pathway kinase （FAM20C） based on their distinctive Ser-x-Glu （S-x-E） motifs. Fam2OC-knockout mice show severe enamel defects similar to those in the Enam-knockout mice, implying an important role of the pSers in ENAM. To determine the role of pSer5s in ENAM, we characterized ENAMRgsc514 mice, in which Sers5 cannot be phosphorylated by FAM20C due to an E57〉Gs7 mutation in the S-x-E motif, The enamel microstructure of 4-week-old mice was examined by scanning electron microscopy. The teeth of 6-day-old mice were characterized by histology and immunohistochemistry. The protein lysates of the first lower molars of 4-day-old mice were analyzed by Western immunoblotting using antibodies against ENAM, ameloblastin and amelogenin. ENAMRgsc514 heterozygotes showed a disorganized enamel microstructure, while the homozygotes had no enamel on the dentin surface. The N-terminal fragments of ENAM in the heterozygotes were detained in the ameloblasts and localized in the mineralization front of enamel matrix, while those in the WT mice were secreted out of ameloblasts and distributed evenly in the outer 1/2 of enamel matrix. Surprisingly, the 15 kDa C-terminal fragments of ameloblastin were not detected in the molar lysates of the homozygotes. These results suggest that the phosphorylation of SerSS may be an essential posttranslational modification of ENAM and is required for the interaction with other enamel matrix molecules such as ameloblastin in mediating the structural organization of enamel matrix and protein-mineral interactions during enamel formation.

关键词： ameloblastin enamel enamelin FAM20C phosphorylation phosphoserine

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Bone morphogenetic protein 2-induced human dental pulp cell differentiation involves p38 mitogen-activated protein kinase-activated canonical WNT pathway

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International Journal of Oral Science 2015年第2期7卷 95-102页

作者： Jing Yang Ling Ye Tian-Qian Hui Dong-Mei Yang Ding-Ming Huang Xue-Dong Zhou Jeremy J Mao Cheng-Lin Wang State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan University center for craniofacial Regeneration(CCR) Columbia University Medical Center

Both bone morphogenetic protein 2（BMP2） and the wingless-type MMTV integration site（WNT）/p-catenin signalling pathway play important roles in odontoblast differentiation and ***-talk between BMP2 and WNT/p-catenin in osteoblast differentiation and bone formation has been ***,the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely ***,we demonstrate that BMP2 promotes the differentiation of human dental pulp cells（HDPCs） by activating WNT/p-catenin signalling,which is further mediated by p38mitogen-activated protein kinase（MAPK） in ***2 stimulation upregulated the expression of p-catenin in HDPCs,which was abolished by SB203580 but not by Noggin or ***,BMP2 enhanced cell differentiation,which was not fully inhibited by Noggin or ***,SB203580 partially blocked BMP2-induced p-catenin expression and cell *** together,these data suggest a possible mechanism by which the elevation of p-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway,which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.

关键词： dental catenin morphogenetic stimulation canonical inhibited blocked repair activating mitogen

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Polymeric vs hydroxyapatite-based scaffolds on dental pulp stem cell proliferation and differentiation

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World Journal of Stem Cells 2015年第10期7卷 1215-1221页

作者： Arash Khojasteh Saeed Reza Motamedian Maryam Rezai Rad Mehrnoosh Hasan Shahriari Nasser Nadjmi Oral and Maxillofacial Surgery Dental Research CenterResearch Institute of Dental SciencesSchool of DentistryShahid Beheshti University of Medical Sciences Dental research center Research Institute of Dental SciencesSchool of DentistryShahid Beheshti University of Medical Sciences the Team for Cleft and craniofacial Anomalies Oral and Maxillofacial SurgeryUniversity of Antwerp

AIM: To evaluate adhesion, proliferation and differentiation of human dental pulp stem cells(h DPSCs) on four commercially available scaffold biomaterials. METHODS: hD PSCs were isolated from human dental pulp tissues of extracted wisdom teeth and established in stem cell growth medium. h DPSCs at passage 3-5 were seeded on four commercially available scaffold biomaterials, SureO ss(Allograft), Cerabone(Xenograft), PLLA(Synthetic), and OSTEON Ⅱ Collagen(Composite), for 7 and 14 d in osteogenic medium. Cell adhesion and morphology to the scaffolds were evaluated by scanning electron microscopy(SEM). Cell proliferation and differentiation into osteogenic lineage were evaluated using DNA counting and alkaline phosphatase(ALP) activity assay, respectively. RESULTS: All scaffold biomaterials except Sure Oss(Allograft) supported h DPSC adhesion, proliferation and differentiation. hD PSCs seeded on PLLA(Synthetic) scaffold showed the highest cell proliferation and attachment as indicated with both SEM and DNA counting assay. Evaluating the osteogenic differentiation capability of hD PSCs on different scaffold biomaterials with ALP activity assay showed high level of ALP activity on cells cultured on PLLA(Synthetic) and OSTEON ⅡCollagen(Composite) scaffolds. SEM micrographs also showed that in the presence of Cerabone(Xenograft) and OSTEON Ⅱ Collagen(Composite) scaffolds, the h DPSCs demonstrated the fibroblastic phenotype with several cytoplasmic extension, while the cells on PLLA scaffold showed the osteoblastic-like morphology, round-like shape. CONCLUSION: PLLA scaffold supports adhesion, proliferation and osteogenic differentiation of hD PSCs. Hence, it may be useful in combination with hD PSCs for cell-based reconstructive therapy.

关键词： Human dental pulp stem cell Stem cell Tissue engin

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