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A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface

International Journal of Oral Science 2024年第2期16卷 225-237页

作者： William Macalester Asme Boussahel Rafael O.Moreno-Tortolero Mark R.Shannon Nicola West Darryl Hill Adam Perriman school of Cellular and Molecular Medicine Biomedical Sciences BuildingUniversity of BristolUniversity WalkBristolUnited Kingdom bristol Centre for Functional Nanomaterials HH Wills Physics LaboratoryUniversity of BristolTyndall AvenueBristolUnited Kingdom Centre for Protolife Research School of ChemistryUniversity of BristolCantocks CloseBristolUnited Kingdom Max Planck-bristol Centre for Minimal Biology School of ChemistryUniversity of BristolBristolUnited Kingdom Periodontology Bristol Dental SchoolUniversity of BristolLower Maudlin StreetBristolUnited Kingdom

Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral ***,the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering,exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems,which will impact on cell fate and subsequent treatment ***,we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells(hMSCs)encapsulated in a microporous hydrogel *** demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs,and that both dentine andβ-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface,which is distal to the gel-substrate *** findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.

关键词： interface den surface

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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

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Caspase-11 mediated inflammasome activation in macrophages by systemic infection of *** exacerbates arthritis

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International Journal of Oral Science 2024年第3期16卷 499-514页

作者： Tokuju Okano Hiroshi Ashida Noriko Komatsu Masayuki Tsukasaki Tamako Iida Marie Iwasawa Yuto Takahashi Yasuo Takeuchi Takanori Iwata Miwa Sasai Masahiro Yamamoto Hiroshi Takayanagi Toshihiko Suzuki Department of Bacterial Pathogenesis Infection and Host ResponseGraduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Lifetime Oral Health Care Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Periodontology Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunoparasitology Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan

Clinical studies have shown that Aggregatibacter actinomycetemcomitans(***)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly ***,we show that systemic infection with *** triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in *** administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in *** data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with *** work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with ***.

关键词： CD11b inflam infection

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PRX1-positive mesenchymal stem cells drive molar morphogenesis

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International Journal of Oral Science 2024年第2期16卷 293-305页

作者： Xiaoqiao Xu Xuyan Gong Lei Zhang Han Zhang Yao Sun Department of Implantology Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghaiChina

Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be *** merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1^(+)cells within *** PRX1^(+)cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell *** into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1^(+)cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling *** loss of Wnt5a exhibits a defect phenotype similar to that of *** addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth *** findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

关键词： Wnt5a mesenchymal inhibited

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Regulating Blood Clot Fibrin Films to Manipulate Biomaterial-Mediated Foreign Body Responses

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Research 2024年第2期2023卷 565-581页

作者： Yang Zou Zhengjie Shan Zongpu Han Jieting Yang Yixiong Lin Zhuohong Gong Lv Xie Jieyun Xu Runlong Xie Zhuofan Chen Zetao Chen Hospital of Stomatology Guanghua School of StomatologySun Yat-sen University and Guangdong Research Center for Dental and Cranial Rehabilitation and Material EngineeringGuangzhou 510055China

The clinical efficacy of implanted biomaterials is often compromised by host immune recognition and subsequent foreign body responses(FBRs).During the implantation,biomaterials inevitably come into direct contact with the blood,absorbing blood protein and forming blood *** studies have been carried out to regulate protein adsorption,thus manipulating ***,the role of clot surface fibrin films formed by clotting shrinkage in host reactions and FBR is often *** of the principle of fibrin film formation being relevant to fibrinogen or clotting factor absorption,it is feasible to manipulate the fibrin film formation via tuning the absorption of fibrinogen and clotting *** biological hydroxyapatite reserved bone architecture and microporous structure,the smaller particle size may expose more microporous structures and adsorb more fibrinogen or clotting ***,we set up 3 sizes(small,<0.2 mm;medium,1 to 2 mm;large,3 to 4 mm)of biological hydroxyapatite(porcine bone-derived hydroxyapatite)with different microporous structures to investigate the absorption of blood protein,the formation of clot surface fibrin films,and the subsequent *** found that small group adsorbed more clotting factors because of more microporous structures and formed the thinnest and sparsest fibrin *** thinnest and sparsest fibrin films increased inflammation and profibrosis of macrophages through a potential signaling pathway of cell adhesion-cytoskeleton-autophagy,leading to the stronger *** group adsorbed lesser clotting factors,forming the thickest and densest fibrin films,easing inflammation and profibrosis of macrophages,and finally mitigating ***,this study deepens the understanding of the role of fibrin films in host recognition and FBR and demonstrates the feasibility of a strategy to regulate FBR by modulating fibrin films via tuning the absorption of blood proteins.

关键词： Blood subsequent biomaterials

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Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： Yang Li Shu-ting Yang Shuying Yang Department of Basic&Translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopaedic Surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA Center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn Center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic *** recent decades,AML patients are significantly *** 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to ***’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 *** great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality *** importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for ***,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

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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.

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The circadian clock in enamel development

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International Journal of Oral Science 2024年第3期16卷 371-380页

作者： Ke Wu Xiaochan Li Yunyang Bai Boon Chin Heng Xuehui Zhang Xuliang Deng Department of Geriatric Dentistry Peking University School and Hospital of StomatologyBeijingChina 4th Division Peking University School and Hospital of StomatologyBeijingChina Department of dental Materials&dental Medical Devices Testing Center Peking University School and Hospital of StomatologyBeijingChina National Engineering Research Center of Oral Biomaterials and Digital Medical Devices NMPA Key Laboratory for Dental MaterialsBeijing Laboratory of Biomedical Materials&Beijing Key Laboratory of Digital StomatologyPeking University School and Hospital of StomatologyBeijingChina Oral Translational Medicine Research Center Joint Training base for Shanxi Provincial Key Laboratory in Oral and Maxillofacial Repair Reconstruction and Regeneration The First People’s Hospital of Jinzhong JinzhongChina

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological *** circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external *** enamel is a type of mineralized tissue that forms the exterior surface of the tooth *** Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian *** enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during *** review will first examine the key roles of the circadian clock in regulating ameloblasts and *** physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and ***,the potential detrimental effects of circadian rhythm disruption on enamel formation are *** rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis ***,future research trajectory in this field is *** is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.

关键词： enamel crown exterior

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The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in early phase of cutting maneuvers in female athletes

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Journal of Sport and Health Science 2024年第3期13卷 376-386页

作者： Issei Ogasawara Ken Ohta Gajanan S.Revankar Shoji Konda Yohei Shimokochi Hideyuki Koga Ken Nakata Department of Health and Sport Sciences Graduate School of MedicineOsaka UniversityToyonaka 560-0043Japan Sports Sensing Co. LTD.Fukuoka 815-0035Japan Department of Neurology Graduate School of MedicineOsaka UniversitySuita 565-0871Japan Department of Health and Sport Management Osaka University of Health and Sport SciencesSennan-gun 590-0496Japan Department of Joint Surgery and Sports Medicine Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8519Japan

Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric *** utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as ***,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still ***:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational ***,we tested a stochastic aspect of our theory in a lab-controlled in vivo *** females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was *** trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial ***:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical ***:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the com

关键词： Center of pressure Deterministic condition Foot strike pattern Injury mechanism Moment of ground reaction force

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Stevens–Johnson syndrome and toxic epidermal necrolysis: Updates in pathophysiology and management

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中华医学杂志(英文版) 2024年第19期137卷 2024 Sep 5页

作者： Hasegawa Akito Abe Riichiro Division of Dermatology Niigata University Graduate School of Medical and Dental Sciences Niigata-8510 Japan

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions characterized by extensive detachment of the epidermis and mucous membranes. These severe disorders carry a high mortality rate, and their pathogenesis remains largely unclear. Furthermore, optimal therapeutic strategies for SJS/TEN remain a subject of ongoing debate. Early diagnosis of SJS/TEN is challenging, and reliable biomarkers for diagnosis or severity prediction have not been firmly established. Certain drugs, such as carbamazepine and allopurinol, have shown a strong association with specific human leukocyte antigen (HLA) types. Recently, the potential benefits of HLA screening prior to administering these drugs to reduce the incidence of SJS/TEN have been explored. Epidermal cell death in SJS/TEN lesions is caused by extensive apoptosis, primarily through the Fas–Fas ligand (FasL) and perforin/granzyme pathways. Our findings suggest that necroptosis, a form of programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, interacts with the formyl peptide receptor 1 to induce necroptosis. Several biomarkers, such as CC chemokine ligand (CCL)-27, interleukin-15, galectin-7, receptor-interacting protein kinases 3 (RIP3), and lipocalin-2, have been identified for diagnostic and prognostic purposes in SJS/TEN. Supportive care is recommended for treating SJS/TEN, but the efficacy of various therapeutic options–including systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and tumor necrosis factor-α antagonists–remains controversial. Recent studies have investigated the potential benefits of tumor necrosis factor-α antagonists. In this review, we discuss recent advances in the understanding and management of SJS/TEN.

关键词： Stevens-Johnson syndrome Toxic epidermal necrolysis Necroptosis Apoptosis

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