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生物陶瓷支架的功能改性及应用研究进展

无机材料学报 2020年第8期35卷 867-881页

作者：董少杰王旭东沈国芳王晓虹林开利同济大学口腔医学院上海牙组织修复与再生工程技术研究中心上海200072 上海交通大学医学院附属第九人民医院上海200011 上海健康医学院上海201318

生物陶瓷支架具有良好的生物相容性和引导组织再生特性,并可提供多孔的表面形貌和孔道结构,以促进新生组织的长入,在硬组织修复和骨组织工程支架领域获得了广泛的关注和临床应用。当前,生物陶瓷支架仍然存在骨诱导活性差、生物功能单一... 详细信息

生物陶瓷支架具有良好的生物相容性和引导组织再生特性,并可提供多孔的表面形貌和孔道结构,以促进新生组织的长入,在硬组织修复和骨组织工程支架领域获得了广泛的关注和临床应用。当前,生物陶瓷支架仍然存在骨诱导活性差、生物功能单一、力学性能差等缺陷,极大限制了它们的临床治疗效果和应用范围。本文从生物陶瓷支架的功能改性角度出发,对材料实施表面功能涂层修饰、微纳结构改性、功能元素掺杂、力学增强等策略,及其在改善植入体生物相容性、促进成骨活性、药物递送、抗肿瘤和抗菌等方面的应用进展进行了归纳和总结,并对功能改性生物陶瓷支架的未来发展趋势作了展望。

关键词：生物陶瓷骨组织工程支架表面改性微纳结构改性元素掺杂改性药物递送综述

The synergistic effect of 3D-printed microscale roughness surface and nanoscale feature on enhancing osteogenic differentiation and rapid osseointegration

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Journal of Materials Science & Technology 2021年第4期63卷 18-26页

作者： Hui Wang Jiaqiang Liu Chengtao Wang steve Guofang shen Xudong Wang Kaili Lin Department of Oral and Cranio-maxillofacial Surgery Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghai200011China School&Hospital of Stomatology Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai200072China School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai200240China Shanghai University of Medicine&Health Sciences Shanghai201318China

Personalized precision therapy and rapid osseointegration are the main development directions of dental implants.3 D printing is a vital advanced manufacturing technology for personalized precision ***,the osteogenesis of the 3 D printed Ti6 Al4 V implants is *** the bionic perspective,the hierarchical micro/nano-topography can mimic the microenvironment of the multilevel structure of natural bone tissue and may endow the implant surface with superior *** the present study,the hierarchical micro/nano-topography was successfully fabricated by construction the nanoscale feature on 3 D printed microscale roughness surface of 3 D-printed Ti6 Al4 V implants by alkali-heat treatment and hydrothermal *** the cell biological responses in vitro and osseointegration performance in vivo were systematically *** hierarchical micro/nano-topography evidently increased the roughness,improved the hydrophilicity and accelerated the hydroxyapatite deposition and mineralization,which significantly enhanced the adhesion,differentiation and extracellular matrix mineralization of bone marrow derived mesenchymal stromal cells(BMSCs).Most importantly,the hierarchical micro/nano-topography on 3 D-printed implants facilitated the new bone formation and rapid osseointegration in *** study suggested that 3 D-printed implant with micro/nano-topography may be a promising candidate to be applied in orthopedic field to meet the need of customized therapy and rapid osseointegration.

关键词： rapid roughness topography

Overexpression of Dlx2 enhances osteogenic differentiation of BMSCs and MC3T3-E1 cells via direct upregulation of Osteocalcin and Alp

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International Journal of Oral Science 2019年第2期11卷 119-130页

作者： Jianfei Zhang Wenbin Zhang Jiewen Dai Xudong Wang steve Guofang shen Department of Oral & Cranio-maxillofacial Surgery Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology

Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial *** aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 ***,we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 ***,Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell *** addition,micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in ***,Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2,Dlx5,Msx2,and Osterix,but led to upregulation of Alp and Osteocalcin (OCN),both of which play critical roles in promoting osteoblast ***,luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter *** chromatin-immunoprecipitation assay and site-directed mutagenesis analysis,we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two *** on these findings,we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene,suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.

关键词： BMSCs MC3T3-E1 Osteocalcin

Perinatal stem cells: A promising cell resource for tissue engineering of craniofacial bone

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World Journal of Stem Cells 2015年第1期7卷 149-159页

作者： Jia-Wen Si Xu-Dong Wang steve GF shen Department of Oral and Craniomaxillofacial Science Shanghai Ninth People’s Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine

In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.

关键词： Craniofacial bone regeneration Bone tissueengineering Extraembryonic tissue Perinatal stem cells

Productivity Gap and Inward FDI Spillovers: Theory and Evidence from China

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China & World Economy 2021年第2期29卷 24-48页

作者： Jim Huangnan shen Hao Wang steve Chu-Chia Lin School of Management Fudan UniversityChina Center for International Development Harvard Kennedy SchoolUS School of Economics and Trade Guangdong University of Foreign StudiesChina School of Slavonic and East European Studies University College LondonUK Department of Economics National Chengchi UniversityTaiwanChina

This paper constructs a two-stage sequential game model to shed light on the spillover effect of inward FDI on the efficiency of domestic firms in host *** model shows that,given an optimal joint-venture policy made by foreign firms,the impact of the spillover effect of inward FDI is contingent upon the productivity gap between the domestic firms and foreign *** particular,we demonstrate that the spillover effect of inward FDI varies negatively with the productivity gap between domestic lowproductivity firms and foreign firms but works in the opposite way for high-productivity *** suggests that once the productivity gap widens,the entry of foreign firms will increase the efficiency of high-productivity firms but reduce the efficiency of lowproductivity *** support of our theoretical model,we provide robust empirical results by using the dataset of annual survey of Chinese industrial enterprises.

关键词： efficiency improvement inward FDI productivity gap spillover effect

Macrophage-derived small extracellular vesicles promote biomimetic mineralized collagen-mediated endogenous bone regeneration

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International Journal of Oral Science 2020年第4期12卷 317-326页

作者： Anqi Liu Shanshan Jin Cuicui Fu shengji Cui Ting Zhang Lisha Zhu Yu Wang steve G.F.shen Nan Jiang Yan Liu Department of Oral and Maxillofacial Surgery Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Key Laboratory of StomatologyShanghaiChina Laboratory of Biomimetic Nanomaterials Department of OrthodonticsPeking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijingChina Department of Oral Biochemistry Academic Centre for Dentistry Amsterdam(ACTA)University of Amsterdam(UvA)and Vrije Universiteit Amsterdam(VU)Gustav Mahlerlaan 3004AmsterdamThe Netherlands Shanghai University of Medicine and Health Sciences ShanghaiChina Central Laboratory Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijingChina

Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still ***,we evaluated intracellular communication through small extracellular vesicles(sEVs)and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen(IMC).After implantation in the bone defect area,IMC generated more neobone and recruited more mesenchymal stem cells(MSCs)than did extrafibrillarly mineralized collagen(EMC).More CD63+CD90+and CD63+CD163+cells were detected in the defect area in the IMC group than in the EMC *** determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological ***,macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2,BGLAP,COL1,and OSX and calcium nodule ***,sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway,and blocking sEV secretion with GW4869 significantly impaired MSC proliferative,immunomodulative and osteogenic *** together,these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.

关键词： endogenous CD63 mediated

Magnesium-containing bioceramics stimulate exosomal miR-196a-5p secretion to promote senescent osteogenesis through targeting Hoxa7/MAPK signaling axis

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Bioactive Materials 2024年第3期33卷 14-29页

作者： Lei Qi Xin Fang Jinge Yan Cancan Pan Weiwen Ge Jing Wang steve GF.shen Kaili Lin Lei Zhang Department of Oral&Cranio-Maxillofacial Surgery Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghai200011PR China National Clinical Research Center for Oral Diseases Shanghai200011PR China Shanghai Key Laboratory of Stomatology&Shanghai Research Institute of Stomatology Shanghai200011PR China Shanghai University of Medicine and Health Sciences Shanghai201318PR China

Stem cell senescence is characterized by progressive functional dysfunction and secretory phenotypic changes including decreased proliferation,dysfunction of osteogenic and angiogenic differentiation,increased secretion of the senescence-associated secretory phenotype(SASP),which bring difficulties for bone *** or delaying senescence of aged bone marrow mesenchymal stem cells(O-BMSCs)was considered as effective strategy for bone regeneration in aging ***(Mg)ion released from bioceramics was reported to facilitate bone regeneration via enhancing osteogenesis and alleviating *** this study,Akermanite biocreamics(Akt)containing Mg ion as a model was demonstrated to promote osteogenesis and angiogenesis effects of O-BMSCs by activating the MAPK signaling pathway in ***,the enhanced osteogenesis effects might be attributed to enhanced Mg-containing Akt-mediated exosomal miR-196a-5p cargo targeting Hoxa7 and activation of MAPK signaling ***,the in vivo study confirmed that 3D-printed porous Mg-containing Akt scaffolds effectively increased bone regeneration in cranial defects of aged *** current results indicated that the exosomal-miR-196a-5p/Hoxa7/MAPK signaling axis might be the potential mechanism underlying Akt-mediated *** exosome-meditaed therapy stimulated by the released Mg ion contained in Akt biocreamics or other biomaterials might serve as a candidate strategy for bone repair in aged individuals.

关键词： Magnesium Akermanite Senescent osteogenesis Exosomal miR-196a-5p Hoxa7/MAPK axis

Reducing relapse and accelerating osteogenesis in rapid maxillary expansion using an injectable mesoporous bioactive glass/fibrin glue composite hydrogel

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Bioactive Materials 2022年第12期7卷 507-525页

作者： Hanjiang Zhao Xiangyu Wang Anting Jin Minjiao Wang Zeying Wang Xingtai Huang Jiewen Dai Xudong Wang Dan Lin steve GF.shen Department of Oral&Cranio-Maxillofacial Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghai200011PR China Shanghai University of Medicine and Health Sciences Shanghai201318China

Rapid maxillary expansion(RME),as a common treatment for craniomaxillofacial deformity,faces the challenge of high relapse rates and unsatisfactory therapeutic *** this study,a standardized Sprague-Dawley(SD)rat RME model was first established with a modified expander as well as retainer design and optimized anterior maxillary expanding force of 100 g which exerted the most synchronized mobility of mid-palatal suture and *** the standardized model,the high relapse rate was proven to be attributed to insufficient osteogenesis in expanded suture,requiring long-term retainer wearing in clinical *** reduce the relapse rate,mesoporous bioactive glass/fibrin glue(MBG/FG)composite hydrogels were developed for an in situ minimal invasive injection that enhance osteogenesis in the expanded *** component of 1 wt%MBG was adopted for enhanced mechanical strength,matched degradation rate and ion dissolution,excellent in vitro biocompatibility and *** of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized *** results demonstrated that injection of 1%MBG/FG composite hydrogel significantly promoted bone formation within the expanded mid-palatal suture,inhibited osteoclastogenesis and benefited the balance of bone remodeling towards *** of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after *** model establishment and the composite hydrogel development in this article might provide new insight to other craniomaxillofacial deformity treatment and design of bone-repairing biomaterials with higher regenerative efficiency.

关键词： Rapid maxillary expansion Sutural distraction osteogenesis Injectable hydrogel Mesoporous bioactive glass Bone regeneration

Different people,different wild:Comparing and mapping wilderness representation in Wuyishan National Park,China

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Geography and Sustainability 2024年第1期5卷 144-156页

作者： Aifang Weng Lingyun Liao Yue Cao steve Carver Li Lin Siyuan shen Zhengduo Xu Jianwen Dong Siren Lan Rui Yang College of Landscape Architecture and Art Fujian Agriculture and Forestry UniversityFuzhou 350002China College of Geographical Science Fujian Normal UniversityFuzhou 350117China Institute of Wuyishan National Park Fuzhou 350002China Department of Landscape Architecture School of ArchitectureTsinghua UniversityBeijing 100084China Institute for National Parks Tsinghua UniversityBeijing 100084China Wildland Research Institute School of GeographyUniversity of LeedsLeedsUK

It is essential to better integrate wilderness representations of different stakeholders into wilderness *** way in which local residents and other stakeholders frame the construction of wilderness of protected areas in developing countries are poorly *** these areas,land use policy and decision may lead to *** study aims to explore existing public wilderness representations using a questionnaire survey(n=514)administered amongst tourists and other stakeholders in the Wuyishan National Park,in southeast *** spatial differences in public representations of wilderness across different stakeholder groups were compared against expert *** found that integrated wilderness representation maps of different stakeholder groups were consistent,namely'area where wild animals live','area with no human influence','a barren and lonely area'.However,three sub-representations of the individual stakeholders varied ***,expert-based wilderness mapping did not reflect public representations accurately,and an integrated wilder-ness quality map considering wilderness representations across both stakeholders and experts can better identify detailed wilderness *** study provides new insights and technical support for future exploration of wilder-ness conservation and mapping in China and other countries with insufficient awareness of wilderness values and investigations in a regional scale.

关键词： Wilderness mapping Public participation Environment perception Protected areas