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Cellular & Molecular Immunology 2021年第9期18卷 2224-2235页

作者： Zongshan Shen Shuhong kuang Min Zhang Xin huang Jiayao Chen Meiliang Guan Wei Qin hockin h.k.xu Zhengmei Lin hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhouGuangdongChina Department of Andrology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina The key Laboratory for Stem Cells and Tissue Engineering Center for Stem Cell Biology and Tissue EngineeringMinistry of EducationSun Yat-sen UniversityGuangzhouGuangdongChina Department of Advanced Oral Sciences&Therapeutics University of Maryland School of DentistryBaltimoreMDUSA Center for Stem Cell Biology and Regenerative Medicine University of Maryland School of MedicineBaltimoreMDUSA University of Maryland Marlene and Stewart Greenebaum Cancer Center University of Maryland School of MedicineBaltimoreMDUSA

Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from *** is caused by diabetes-enhanced host immune-inflammatory responses to bacterial *** this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to ***,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal ***,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic *** finding provides a basis for the development of an effective therapeutic approach for treating DP.

关键词： Diabetes-associated periodontitis bindarit proinflammatory monocytes macrophages

Induced Pluripotent Stem Cell-derived Mesenchymal Stem Cell Seeding on Biofunctionalized Calcium Phosphate Cements

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Bone Research 2013年第4期1卷 371-384页

作者： WahWah Theinhan Jun Liu Minghui Tang Wenchuan Chen Linzhao Cheng hockin h.k.xu Biomaterials & Tissue Engineering Division Department of EndodonticsProsthodontics and Operative DentistryUniversity of Maryland Dental School State key Laboratory of Oral Diseases West China Hospital of StomatologySichuan University Stem Cell Program in Institute for Cell Engineering and Division of hematology Johns Hopkins University Center for Stem Cell Biology & Regenerative Medicine University of Maryland School of Medicine University of Maryland Marlene and Stewart Greenebaum Cancer Center University of Maryland School of Medicine Department of Mechanical Engineering University of Maryland

Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.

关键词： induced pluripotent stem cells RGD fibronectin platelet concentrate biofunctionalized calciumphosphate cement bone tissue engineering

Effects of water-aging for 6 months on the durability of a novel antimicrobial and protein-repellent dental bonding agent

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International Journal of Oral Science 2018年第3期10卷 160-167页

作者： Ning Zhang ke Zhang Michael D.Weir David J.xu Mark A.Reynolds Yuxing Bai hockin h.k.xu Department of Orthodontics School of StomatologyCapital Medical UniversityBeijingChina Biomatexrials&Tissue Engineering Division Department of EndodonticsPeriodontics and ProsthodonticsUniversity of Maryland Dental SchoolBaltimoreMDUSA Center for Stem Cell Biology&Regenerative Medicine University of Maryland School of MedicineBaltimoreMDUSA Marlene and Stewart Greenebaum Cancer Center University of Maryland School of MedicineBaltimoreMDUSA Department of Mechanical Engineering University of MarylandBaltimore CountyMDUSA

Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate(DMAhDM) and 2-methacryloyloxyethyl phosphorylcholine(MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent(MPC) and antibacterial agent(DMAhDM) were added to a Scotchbond multi-purpose(SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days(d).At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAhDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control(P he SBMP + MPC + DMAhDM group had protein adhesion that was only 1/20 of that of the SBMP control(P hDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d(P > 0.1). In conclusion, a bonding agent with MPC and DMAhDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.

关键词： MPC Effects of water-aging for 6 months on the durability of a novel antimicrobial and protein-repellent dental bonding agent

3D-printed Mechanically Strong Calcium Phosphate Cement Scaffold with Metformin/Stem Cell-encapsulating Alginate Microbeads for Bone Tissue Engineering

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Journal of Bionic Engineering 2022年第6期19卷 1658-1670页

作者： Xiong Xiong Yuanyuan Chen Rupan Yuan Gengtao Qiu Michael D.Weir hockin h.k.xu Jin Liu Jianping Ruan Xiaofeng Chang Shuxin Qu School of Life Science and Engineering Southwest Jiaotong UniversityChengdu610031China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China key Lab of Advanced Technologies of Materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China Department of Advanced Oral Sciences and Therapeutics University of Maryland School of DentistryBaltimoreMD21201USA Center for Stem Cell Biology and Regenerative Medicine University of Maryland School of MedicineBaltimoreMD21201USA University of Maryland Marlene and Stewart Greenebaum Cancer Center University of Maryland School of MedicineBaltimoreMD21201USA key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research Clinical Research Center of Shannxi Province for Dental and Maxillofacial DiseasesCollege of StomatologyXi’an Jiaotong UniversityXi’anShannxi710004China

The utilization of Calcium Phosphate Cement(CPC)is limited due to its low mechanical strength and difficulty to seed cells deep into the *** objectives of this study were to:(1)develop a 3D-printed CPC-dopamine-metformin scaffold encapsulating human periodontal ligament stem cells(hPDLSCs),(2)investigate the effect of dopamine on the performance of CPC,and(3)evaluate the effect of microbead degradation and metformin release on the osteogenic differentiation of the released *** mechanical property of the CPC scaffolds was elevated by adding dopamine,and the CPC scaffold with 7 wt.%dopamine had the highest compressive strength(7.35 MPa).Four types of microbeads with different content of alginate(oxidized alginate),hPDLSCs,and 2%metformin were *** and cell counting kit tests confirm that the hPDLSCs are protected by microbeads encapsulation during the CPC setting *** alkaline phosphatase test indicates that the osteogenic differentiation of hPDLSCs was enhanced by the fast release of cells and *** microbeads consisting of 2%oxidized alginate and 2%metformin were optimal for cell delivery due to favorable cell release and osteogenic *** CPC scaffold is promising used for bone regeneration in dental,craniofacial,and orthopedic applications.

关键词： Calcium phosphate cement 3D Printing Bionic Alginate microbeads Metformin

Toward dental caries: Exploring nanoparticle-based platforms and calcium phosphate compounds for dental restorative materials

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Bioactive Materials 2019年第1期4卷 43-55页

作者： Abdulrahman A.Balhaddad Anmar A.kansara Denise hidan Michael D.Weir hockin h.k.xu Mary Anne S.Melo Ph.D.Program in Biomedical Sciences University of Maryland School of DentistryBaltimoreMD21201USA Division of Biomaterials&Tissue Engineering Department of Advanced Oral Sciences and TherapeuticsUniversity of Maryland School of DentistryBaltimoreMD21201USA Department of Restorative Dental Sciences Imam Abdulrahman Bin Faisal UniversityCollege of DentistryDammamSaudi Arabia Department of Restorative Dentistry Umm Al-Qura UniversityCollege of DentistryMakkahSaudi Arabia Division of Operative Dentistry Dept.of General DentistryUniversity of Maryland School of DentistryBaltimoreMD21201USA

Millions of people worldwide suffer from a toothache due to tooth cavity,and often permanent tooth *** caries,also known as tooth decay,is a biofilm-dependent infectious disease that damages teeth by minerals loss and presents a high incidence of clinical restorative polymeric fillings(tooth colored fillings).Until now,restorative polymeric fillings present no *** complexity of oral biofilms contributes to the difficulty in developing effective novel dental *** has been explored in the development of bioactive dental materials to reduce or modulate the activities of caries-related ***-structured platforms based on calcium phosphate and metallic particles have advanced to impart an anti-caries potential to restorative *** bioactivity of these platforms induces prevention of mineral loss of the hard tooth structure and antibacterial activities against caries-related *** has been suggested that this bioactivity could minimize the incidence of caries around restorations(CARS)and increase the longevity of such filling *** last few years witnessed growing numbers of studies on the preparation evaluations of these novel ***,the caries disease process and the role of pathogenic caries-related biofilm,the increasing incidence of CARS,and the recent efforts employed for incorporation of bioactive nanoparticles in restorative polymer materials as useful strategies for prevention and management of caries-related-bacteria are *** highlight the status of the most advanced and widely explored interaction of nanoparticle-based platforms and calcium phosphate compounds with an eye toward translating the potential of these approaches to the dental clinical reality.

关键词： Dental materials Bioactive Nanoparticles Dental caries

Dental remineralization via poly(amido amine) and restorative materials containing calcium phosphate nanoparticles

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International Journal of Oral Science 2019年第3期11卷 180-191页

作者： kunneng Liang Suping Wang Siying Tao Shimeng Xiao han Zhou Ping Wang Lei Cheng xuedong Zhou Michael D.Weir Thomas W.Oates Jiyao Li hockin h.k.xu State key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Advanced Oral Sciences and Therapeutics University of Maryland School of DentistryBaltimoreMDUSA Department of Operative Dentistry and Endodontics & Stomatology Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Center for Stem Cell Biology & Regenerative Medicine University of Maryland School of MedicineBaltimoreMDUSA Marlene and Stewart Greenebaum Cancer Center University of Maryland School of MedicineBaltimoreMDUSA

Tooth decay is prevalent,and secondary caries causes restoration failures,both of which are related to *** is an urgent need to develop new therapeutic materials with remineralization *** article represents the first review on the cutting edge research of poly(amido amine)(PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP).PAMAM was excellent nucleation template,and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate *** composite and adhesive showed acid-neutralization and Ca and P ion release *** +NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates,superior acidneutralization,and ions ***,the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP ***+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ***,the long-term remineralization capability of PAMAM+NACP was *** prolonged fluid challenge,the immersed PAMAM with the recharged NACP still induced effective dentin mineral ***,the hardness of predemineralized dentin was increased back to that of healthy dentin,indicating a complete ***,the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization,hardness increase,and caries-inhibition capabilities.

关键词： an urgent need calcium phosphate dentin

Advanced smart biomaterials and constructs for hard tissue engineering and regeneration

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Bone Research 2018年第4期6卷 316-330页

作者： ke Zhang Suping Wang Chenchen Zhou Lei Cheng Xianling Gao Xianju Xie Jirun Sun haohao Wang Michael D.Weir Mark A.Reynolds Ning Zhang Yuxing Bai hockin h.k.xu Department of Orthodontics School of Stomatology Capital Medical University Department of Advanced Oral Sciences and Therapeutics University of Maryland Dental School State key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Deptartment of Cariology and Endodonics West China hospital of Stomatology Sichuan University Department of Operative Dentistry and Endodontics Guanghua School of Stomatology Sun Yat-sen University Guangdong Provincial Key Laboratory of Stomatology Volpe Research Center American Dental Association Foundation National Institute of Standards and Technology Center for Stem Cell Biology & Regenerative Medicine University of Maryland School of Medicine Marlene and Stewart Greenebaum Cancer Center University of Maryland School of Medicine

hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. hard tissues include bone and tooth structures that contain calcium phosphate *** biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material’s responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to ph to protect tooth structures; smart ph-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.

关键词： regeneration engineering minerals

Novel dental implant modifications with two-staged double benefits for preventing infection and promoting osseointegration in vivo and in vitro

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Bioactive Materials 2021年第12期6卷 4568-4579页

作者： Xiaoyu huang Yang Ge Bina Yang Qi han Wen Zhou Jingou Liang Mingyun Li Xian Peng Biao Ren Bangcheng Yang Michael D.Weir Qiang Guo haohao Wang Xinxuan Zhou xugang Lu Thomas W.Oates hockin h.k.xu Dongmei Deng xuedong Zhou Lei Cheng State key Laboratory of Oral Diseases West China Hospital of StomatologyNational Clinical Research Center for Oral DiseasesSichuan UniversityChengdu610041China Department of Operative Dentistry and Endodontics West China School of StomatologySichuan UniversityChengdu610041China Stomatological hospital Southern Medical UniversityGuangzhou510280China Department of Pathology West China School of StomatologySichuan UniversityChengdu610041China Department of Pediatrics West China School of StomatologySichuan UniversityChengdu610041China Department of Advanced Oral Sciences and Therapeutics University of Maryland School of DentistryBaltimoreMD21201USA Department of Preventive Dentistry Academic Center for Dentistry Amsterdam(ACTA)University of Amsterdam and VU University AmsterdamAmsterdamthe Netherlands National Engineering Research Center for Biomaterials Sichuan UniversityChengdu610041China

Peri-implantitis are a major problem causing implant failure these ***,anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this ***-arc oxidation(MAO)treatment is a way to form an oxidation film on the surface of metallic *** method shows good osteogenic properties but weak antibacterial ***,we developed combined strategies to combat severe peri-implantitis,which included the use of a novel compound,PD,comprising dendrimers poly(amidoamine)(PAMAM)loading dimethylaminododecyl methacrylate(DMADDM)as well as MAO ***,we explored the chemical properties of the novel compound PD,and proved that this compound was successfully synthesized,with the loading efficiency and encapsulation efficiency of 23.91%and 31.42%,*** further report the two-stage double benefits capability of PD+MAO:(1)in the first stage,PD+MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo;(2)in the second stage,PD+MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in *** study first reports the two-staged,double benefits of PD+MAO,and demonstrates its potential in clinical applications for inhibiting peri-implantitis,especially in patients with severe infection risk.

关键词： Peri-implantitis Dimethylaminododecyl methacrylate Animal model Osseointegration Bioactive and therapeutic

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新型窝沟封闭剂的氟离子释放和抗菌性能研究

新型窝沟封闭剂的氟离子释放和抗菌性能研究

新型可充电磷酸钙树脂的研究初探——离子释放与离子充电

2019年中华口腔医学会口腔预防医学专业委员会第十九次全国学术年会

作者：费秀智张倩 hockin h.k.xu 阮建平西安交通大学口腔医学院·附属口腔医院 Department of Advanced Oral Sciences & Therapeutics University of Maryland School of Dentistry

目的评价一种含甲基丙烯酸十六烷基二甲铵(DMAhDM)和纳米氟化钙(nCaF)的窝沟封闭剂氟离子释放能力及对变形链球菌生物膜的抗菌性能。方法 helioseal F为商品对照组,50%BT+50%Glass为实验对照组,45%BT+5%DMAhDM+20%nCaF+30%Glass为实验... 详细信息

目的评价一种含甲基丙烯酸十六烷基二甲铵(DMAhDM)和纳米氟化钙(nCaF)的窝沟封闭剂氟离子释放能力及对变形链球菌生物膜的抗菌性能。方法 helioseal F为商品对照组,50%BT+50%Glass为实验对照组,45%BT+5%DMAhDM+20%nCaF+30%Glass为实验组。测试釉质剪切强度、氟离子释放量及对变形链球菌UA159 48h生物膜代谢活性、产乳酸能力、死活菌组成及菌落形成单位(CFU)的影响。SPSS18.0进行统计分析。结果实验组和商品对照组间釉质剪切强度无统计学差异(p>0.05),氟离子释放能力显著提高(phDM的窝沟封闭剂具有高氟离子释放能力和良好抗菌性能,具有一定临床应用价值。

关键词：窝沟封闭剂氟释放性能抗菌性能釉质剪切强度

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新型可充电磷酸钙树脂的研究初探——离子释放与离子充电