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Nanoporous titanium implant surface promotes osteogenesis by suppressing osteoclastogenesis via integrin β1/FAKpY397/MAPK pathway

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Bioactive Materials 2022年第2期7卷 109-123页

作者： Yide He Zhe Li Xin Ding Boya Xu Jinjin Wang Yi Li Fanghao Chen Fanhui Meng Wen Song Yumei Zhang State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi key laboratory of Oral Diseases Department of ProsthodonticsSchool of StomatologyThe Fourth Military Medical UniversityXi’anChina Huaian Stomatological Hospital NanjingChina State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi key laboratory of Oral Diseases Department of PeriodontologySchool of StomatologyThe Fourth Military Medical UniversityXi’anChina State Key Laboratory of Military Stomatology Department of Dental MaterialsSchool of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina

Macrophages and osteoclasts are both derived from monocyte/macrophage lineage,which plays as the osteoclastic part of bone metabolism.Although they are regulated by bone implant surface nanoarchitecture and involved in osseointegration,the beneath mechanism has not been simultaneously analyzed in a given surface model and their communication with osteoblasts is also blurring.Here,the effect of implant surface topography on monocyte/macrophage lineage osteoclastogenesis and the subsequent effect on osteogenesis are systematically investigated.The nanoporous surface is fabricated on titanium implant by etching and anodizing to get the nanotubes structure.The early bone formation around implant is significantly accelerated by the nanoporous surface in vivo.Meanwhile,the macrophage recruitment and osteoclast formation are increased and decreased respectively.Mechanistically,the integrin mediated FAK phosphorylation and its downstream MAPK pathway(p-p38)are significantly downregulated by the nanoporous surface,which account for the inhibition of osteoclastogenesis.In addition,the nanoporous surface can alleviate the inhibition of osteoclasts on osteogenesis by changing the secretion of clastokines,and accelerate bone regeneration by macrophage cytokine profiles.In conclusion,these data indicate that physical topography of implant surface is a critical factor modulating monocyte/macrophage lineage commitment,which provides theoretical guidance and mechanism basis for promoting osseointegration by coupling the osteogenesis and osteoclastogenesis.

关键词： Nanoporous implant Osteogenesis Osteoclastogenesis FAK phosphorylation MAPK

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Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

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Bone Research 2024年第1期12卷 137-152页

作者： Weicheng Lu Jianfei Yan Chenyu Wang Wenpin Qin Xiaoxiao Han Zixuan Qin Yu Wei Haoqing Xu Jialu Gao Changhe Gao Tao Ye Franklin R.Tay Lina Niu Kai Jiao Department of stomatology Tangdu Hospital&State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina state key laboratory of Oral and Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi key laboratory of stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina The Dental College of Georgia Augusta UniversityAugustaGAUSA

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

关键词： neurogenic ossification pathogenesis

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Microstructure and Mechanical Properties of Al_2O_3/ZrO_2 Directionally Solidified Eutectic Ceramic Prepared by Laser 3D Printing

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Journal of Materials Science & Technology 2016年第4期32卷 320-325页

作者： Zhi Liu Kan Song Bo Gao Tian Tian Haiou Yang Xin Lin Weidong Huang State Key Laboratory of Military Stomatology Department of Prosthodontics School of Stomatology Fourth Military Medical University state key laboratory of Solidification Processing Northwestern Polytechnical University

Directionally solidified eutectic ceramics such as Al2O3/ZrO2 are promising structural materials for ap- plications in harsh environment with an ultrahigh temperature. In this work, through adopting assistant heating laser 3D printing, Al2O3/ZrO2 eutectic samples were manufactured with suppressing the forma- tion of cracks. The dependence of the average rod spacing （λav） on the scanning rate （V） follows a relation with λavV0.5 = 1 μm1.5 s^-0.5. Typical eutectic microstructures, so-called complex regular, were analyzed with respect to its evolution with modulating the growth conditions. Formation mechanism of the solidifi- cation defect, shrinkage porosity, was discussed and the defect is found to be significantly suppressed by optimizing the solidification parameters. The maximum hardness and fracture toughness are mea- sured to he 16.7 GPa and 4.5 MPa m1/2, respectively. The interplay between the propagation of cracks and the Al2O3/ZrO2 interface is discussed.

关键词： Al2O3 ZrO2 Eutectic Solidification

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The integration of peri-implant soft tissues around zirconia abutments:Challenges and strategies

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Bioactive Materials 2023年第9期27卷 348-361页

作者： Kai Tang Meng-Lin Luo Wei Zhou Li-Na Niu Ji-Hua Chen Fu Wang National Clinical Research Center for Oral Diseases&State Key Laboratory of Military Stomatology&Shaanxi key laboratory of stomatology Department of ProsthodonticsSchool of StomatologyThe Fourth Military Medical UniversityXi’anShaanxi710032China Institute of stomatology&Oral Maxilla Facial key laboratory The First Medical CenterChinese PLA General Hospital&Department of StomatologyThe First Medical CenterChinese PLA General HospitalBeijingChina

Stable soft tissue integration around the implant abutment attenuates pathogen penetration,protects underlying bone tissue,prevents peri-implantitis and is essential in maintaining long-term implant stability.The desire for“metal free”and“aesthetic restoration”has favored zirconia over titanium abutments,especially for implant restorations in the anterior region and for patients with thin gingival biotype.Soft tissue attachment to the zirconia abutment surface remains a challenge.A comprehensive review of advances in zirconia surface treatment(micro-design)and structural design(macro-design)affecting soft tissue attachment is presented and strategies and research directions are discussed.Soft tissue models for abutment research are described.Guidelines for development of zirconia abutment surfaces that promote soft tissue integration and evidence-based references to inform clinical choice of abutment structure and postoperative maintenance are presented.

关键词： Zirconia Implant abutment Surface modification Soft tissue adhesion

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Polyphosphate-crosslinked collagen scaffolds for hemostasis and alveolar bone regeneration after tooth extraction

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Bioactive Materials 2022年第9期7卷 68-81页

作者： Jun-ting Gu Kai Jiao Jing Li Jian-fei Yan Kai-yan Wang Fu Wang Yan Liu Franklin R.Tay Ji-hua Chen Li-na Niu National Clinical Research Center for Oral Diseases State Key Laboratory of Military StomatologyShaanxi Key Laboratory of StomatologyDepartment of ProsthodonticsSchool of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina Department of Endodontics The Dental College of GeorgiaAugusta UniversityAugustaGA30912USA

Post-extraction bleeding and alveolar bone resorption are the two frequently encountered complications after tooth extraction that result in poor healing and rehabilitation difficulties.The present study covalently bonded polyphosphate onto a collagen scaffold(P-CS)by crosslinking.The P-CS demonstrated improved hemostatic property in a healthy rat model and an anticoagulant-treated rat model.This improvement is attributed to the increase in hydrophilicity,increased thrombin generation,platelet activation and stimulation of the intrinsic coagulation pathway.In addition,the P-CS promoted the in-situ bone regeneration and alveolar ridge preservation in a rat alveolar bone defect model.The promotion is attributed to enhanced osteogenic differentiation of bone marrow stromal cells.Osteogenesis was improved by both polyphosphate and blood clots.Taken together,P-CS possesses favorable hemostasis and alveolar ridge preservation capability.It may be used as an effective treatment option for post-extraction bleeding and alveolar bone loss.statement of significance:Collagen scaffold is commonly used for the treatment of post-extraction bleeding and alveolar bone loss after tooth extraction.However,its application is hampered by insufficient hemostatic and osteoinductive property.Crosslinking polyphosphate with collagen produces a modified collagen scaffold that possesses improved hemostatic performance and augmented bone regeneration potential.

关键词： Alveolar ridge preservation Blood clotting Osteogenesis Polyphosphate

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Silicified collagen scaffold induces semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration

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Bioactive Materials 2022年第3期7卷 475-490页

作者： Yu-Xuan Ma Kai Jiao Qian-Qian Wan Jing Li Ming-Yi Liu Zi-Bin Zhang Wen Qin Kai-Yan Wang Ya-zhou Wang Franklin R.Tay Li-Na Niu State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi key laboratory of stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxi710032China Department of Neurobiology The Fourth Military Medical UniversityXi’anShaanxi710032China The Graduate School Augusta UniversityAugustaGA30912USA

Sensory nerves promote osteogenesis through the release of neuropeptides.However,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive.The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats.The wound sites were accompanied by extensive nerve innervation and angiogenesis.Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model.Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A(Sema3A)and semaphorin 4D(Sema4D)in the dorsal root ganglion(DRG),as detected by the upregulation of signaling molecules.Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells.These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies.Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model,whereas overexpression of Sema3A promoted the silicon-induced phenomena.Activation of“mechanistic target of rapamycin”(mTOR)pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds.These findings support the role of silicon in inducing Sema3A production by sensory nerves,which,in turn,stimulates osteogenesis and angiogenesis.Taken together,silicon has therapeutic potential in orthopedic rehabilitation.

关键词： Distal femur defect Mechanistic target of rapamycin Semaphorin 3A Sensory nerve Silicified collagen scaffolds

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Application of fluoride disturbs cariogenic oral microecology and promotes remineralization of enamel initial caries

Application of fluoride disturbs cariogenic oral microecolog...

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中华口腔医学会牙体牙髓病学专业委员会第十四次全国牙体牙...

作者： Qianxia Zhang Lingxia Guan Jing Guo Aiyun Chuan Wei Zhang Shengchao Wang Wenkai Jiang State Key Laboratory of Military Stomatology

Objectives: The caries-preventive effect of topical fluoride application has been corroborated by a considerable number of clinical studies. The objective of this study is to monitor the microbial diversity of supragingival plaque and enamel initial caries after fluoride application in deciduous dentition from the perspective of microbiology and enamel demineralization/remineralization. Methods: Three-yearold children were subjected in the study. Fluoride was applied at baseline and 6 month. Supragingival plaque samples were collected at baseline, on the 3 day and on the 2nd weekend, and 16S rRNA sequencing and bioinformatics analyses were performed. International Caries Detection and Assessment System II(ICDAS II) indices were measured at baseline and on the 3, 6 and 12 month. SPSS 19.0 was used for statistical analysis. Results: Changes in microbial community structure were observed by Beta diversity analysis on the 3 day after the first fluoridation(P0.05). Significant changes in the relative abundance of a variety of microorganisms were observed by LEfSe analysis on the 3 day(P<0.05) with the decreasement of Capnocytophaga and the increasement of Rothia at genus level. The cell movement and energy metabolism might be inhibited as observed by PICRUSt analysis on the 3 day(P<0.05). The mean ICDAS II scores at smooth surface sites presented a significant decreasing trend, which reached a minimum at the 6 month(P<0.05) and slightly recovered at the 12 month. However, no significant change of the scores at occlusal surface sites was detected within 6 months, even significantly higher than the baseline level at the 12 month(P<0.05). The proportion of ICDAS code 0 showed a significant increasing trend(P<0.05) and code 1 showed a significant decreasing trend(P<0.05) after each fluoride application at the site GB, site OB, and site GL. At the site IL, the proportion of code 3-6 significantly increased on the 12 month(P<0.05). At t

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MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts

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International Journal of Oral Science 2023年第1期15卷 63-75页

作者： Qingyuan Ye Xinyu Qiu Jinjin Wang Boya Xu Yuting Su Chenxi Zheng Linyuan Gui Lu Yu Huijuan Kuang Huan Liu Xiaoning He Zhiwei Ma Qintao Wang Yan Jin State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi International Joint Research Center for Oral Diseases Center for Tissue EngineeringSchool of StomatologyAir Force Medical UniversityXi’anChina State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi key laboratory of stomatology Digital Dentistry CenterSchool of StomatologyAir Force Medical UniversityXi’anChina State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral Diseases Department of Preventive DentistrySchool of StomatologyAir Force Medical UniversityXi’anChina State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Department of PeriodontologySchool of StomatologyAir Force Medical UniversityXi’anChina State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi key laboratory of Oral Diseases Department of ProsthodonticsSchool of StomatologyAir Force Medical UniversityXi’anChina Aerospace Clinical Medical Center School of Aerospace MedicineAir Force Medical UniversityXi’anChina Department of Otolaryngology Head and Neck Surgery Peking University Third HospitalBeijingChina

Severe muscle injury is hard to heal and always results in a poor prognosis.Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine,however,whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown.Herein,we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells(MSCs-Apo EVs)to treat cardiotoxin induced tibialis anterior(TA)injury and found that MSCs-Apo EVs promoted muscles regeneration and increased the proportion of multinucleated cells.Besides that,we also found that apoptosis was synchronized during myoblasts fusion and MSCs-Apo EVs promoted the apoptosis ratio as well as the fusion index of myoblasts.Furthermore,we revealed that MSCs-Apo EVs increased the relative level of creatine during myoblasts fusion,which was released via activated Pannexin 1 channel.Moreover,we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived Apo EVs(Myo-Apo EVs)instead of apoptotic myoblasts,and creatine was the pivotal metabolite involved in myoblasts fusion.Collectively,our findings firstly revealed that MSCs-Apo EVs can promote muscle regeneration and elucidated that the new function of Apo EVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel,which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

关键词： apo extracellular release

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New classification of hereditary dentin defects with systemic diseases

New classification of hereditary dentin defects with systemi...

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2023年中华口腔医学会口腔遗传病与罕见病专业委员会第...

作者： Tongyu Su Yulong Zhu Xiangpu Wang Qinglin Zhu Xiaohong Duan State Key Laboratory of Military Stomatology Department of Operative Dentistry and Endodontics School of Stomatology The Fourth Military Medical University & State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology

History:In 1973, Shields classified DI into three subgroups (Ⅰ-Ⅲ) and DD into two groups (DD-Ⅰ and DD-Ⅱ) according to the different clinical manifestations.In 2015, de La Dure-Molla proposed a new two-type classification of hereditary dentin disease to better distinguish DI and DD and their subgroups, i.e., dentinogenesis imperfecta (DI) and radicular dentin dysplasia (Shields’ DD type I).

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Visualization analysis of research frontiers and trends in nerve regeneration and osseoperception in the repair of tooth loss

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Neural Regeneration Research 2014年第22期9卷 2013-2018页

作者： Xiaoge Zhang Tian Tang Zhihe Zhao Leilei Zheng Yin Ding State Key Laboratory of Military Stomatology Department of OrthodonticsSchool of Stomatologythe Fourth Military Medical University state key laboratory of Oral Diseases Department of OrthodonticsWest China Hospital of StomatologySichuan University Department of Orthodontics the Affiliated Hospital of StomatologyChongqing Medical University

This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace Ⅲ software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.

关键词： nerve regeneration tooth nerve injury peripheral nerve injury nerve repair osseoperception neuroprotection scientific map Web of Science Citespace neural regeneration

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