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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 therapy.However,the osteogenesis of the 3 D printed Ti6 Al4 V implants is unsatisfactory.From 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 bioactivity.In 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 treatment.Then the cell biological responses in vitro and osseointegration performance in vivo were systematically evaluated.The 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 vivo.Our 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

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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 tissues.The 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 cells.Initially,we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells.Moreover,Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line.In addition,micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo.Unexpectedly,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 maturation.Importantly,luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity.Through 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 genes.Based 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

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生物陶瓷支架的功能改性及应用研究进展

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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

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Simultaneous gap arthroplasty combined with distraction osteogenesis in the treatment of unilateral temporo-mandibular joint ankylosis with micrognathia deformity

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中国口腔颌面外科杂志 2008年第B5期6卷 172-173页

作者： Hong Bo Yu Steve Guofang Shen Shi Lei Zhang Xu Dong Wang You sheng Tang Oral and Maxillofacial Surgery Ninth People's HospitalShanghai Jiao Tong University Shanghai 200011 China

Purpose: To evaluate the efficacy of simultaneous gap arthroplasty and distraction steogenesis in the treatment of unilateral temporo-mandibular joint ankylosis patients with micrognathia deformity。Methods: During the period January 2000-December 2006, 11 patients with unilateral temporoman- dibular joint ankylosis and micrognathia deformity underwent gap arthroplasty, mandibular osteotomy and distractor implant simultaneously。Mouse opening exercises were performed on the first postoperative day and distraction was started on the fifth postoperative day。Results: All patients had a satisfactory mouse opening on follow-up (35.4:1: 3.5mm)。Facial asymmetry deformities were corrected and satisfactory occlusions were achieved with the help of postoperative orthodontic treatment。Conclusion: distraction osteogenesis and gap arthroplasty can be used simultaneously in patients with temporomandibular ankylosis and micrognathia deformity。

关键词：关节造形术骨发生整形手术关节强直

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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 countries.Our 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 ones.In 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 firms.This 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 firms.In 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

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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 effects.In 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 incisors.Via 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 situations.To 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 palate.The component of 1 wt%MBG was adopted for enhanced mechanical strength,matched degradation rate and ion dissolution,excellent in vitro biocompatibility and osteoinductivity.Effects of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized model.The 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 osteogenesis.Combination of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after RME.The 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

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颗粒酶B在慢性鼓膜穿孔炎症损伤修复中的应用

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中国眼耳鼻喉科杂志 2016年第1期16卷 7-9,15页

作者：张天宇 shen steve 杨琳复旦大学附属眼耳鼻喉科医院耳鼻喉科、上海市听觉医学临床中心英属哥伦比亚大学病理学与实验医学系温哥华V6Z 1Y6 复旦大学附属眼耳鼻喉科医院实验中心复旦大学附属眼耳鼻喉科医院卫生部听觉医学重点实验室上海200031

鼓膜穿孔延缓愈合可导致声波传递增益减少。文献报道颗粒酶B通过细胞内、外途径介导炎症反应,影响或延缓皮肤等伤口愈合;颗粒酶B基因敲除的小鼠则不发生迟缓愈合。鼓膜结构与皮肤有相似性,但在正常鼓膜与损伤延迟愈合鼓膜中颗粒酶B的表... 详细信息

鼓膜穿孔延缓愈合可导致声波传递增益减少。文献报道颗粒酶B通过细胞内、外途径介导炎症反应,影响或延缓皮肤等伤口愈合;颗粒酶B基因敲除的小鼠则不发生迟缓愈合。鼓膜结构与皮肤有相似性,但在正常鼓膜与损伤延迟愈合鼓膜中颗粒酶B的表达差异鲜有报道。本文总结了慢性鼓膜穿孔产生和延迟愈合的机制及颗粒酶B可能对其影响的途径,为研究颗粒酶B抑制剂在促进慢性鼓膜穿孔炎症损伤修复中的作用,为临床探索新的治疗手段提供依据。

关键词：颗粒酶B 鼓膜穿孔炎症反应损伤修复

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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 unclear.Here,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 group.To determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological differences.However,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 formation.Mechanistically,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 potential.Taken 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

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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

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采用电凝增强的“哑铃样”自膨式金属支架在内镜超声引导下实施一步法胰周积液引流:有无荧光辅助的结局比较

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Gastroenterology Report 2020年第6期8卷 425-430,I0001页

作者： Babatunde Olaiya Parit Mekaroonkamol Bai-Wen Li Julia Massaad Cicily TVachaparambil Jennifer Xu Vladamir Lamm Hui Luo Shan-Shan shen Hui-Min Chen steve Keilin Field FWillingham Qiang Cai Department of Internal Medicine Marshfield ClinicMarshfieldWIUSA Division of Digestive Diseases Emory University School of MedicineAtlantaGAUSA Division of Gastroenterology King Chulalongkorn Memorial HospitalChulalongkorn University and Thai Red CrossBangkokThailand Department of Gastroenterology Shanghai General HospitalShanghai Jiaotong UniversityShanghaiP.R.China Department of Gastroenterology Xijing HospitalXi’anShaanxiP.R.China Department of Gastroenterology Nanjing Drum Tower HospitalNanjingJiangshuP.R.China Department of Gastroenterology Renji HospitalShanghai Jiaotong UniversityShanghaiP.R.China

背景:荧光透视技术常用于胰周积液(PFC)的内镜引流。电凝增强的“哑铃样”自膨式金属支架(ELAMS)可实现“一步法”操作,并有可能无需荧光透视。本研究比较了在有或没有荧光透视的协助下,ELAMS的治疗结果。方法:纳入2014年1月至2017年2... 详细信息

背景:荧光透视技术常用于胰周积液(PFC)的内镜引流。电凝增强的“哑铃样”自膨式金属支架(ELAMS)可实现“一步法”操作,并有可能无需荧光透视。本研究比较了在有或没有荧光透视的协助下,ELAMS的治疗结果。方法:纳入2014年1月至2017年2月间行囊肿胃吻合术的PFC患者。基于有无采用荧光透视将入组病例分为两组。技术成功,定义为术中顺利置入ELAMS;临床成功,定义为术后临床症状缓解或8周后CT显示胰腺囊肿缩小75%以上。记录出血、支架移位、感染等不良事件。结果:研究期间共有21例患者采用ELAMS进行PFC引流,其中男性13例。平均年龄(51.6±14.2)岁。13例患者为包裹性坏死,8例为胰腺假性囊肿。PFC平均直径(11.3±3.3)cm。7例(33%)患者术中采用了荧光透视,手术时间显著延长[(43.1±10.4)min vs(33.3±10.5)min,P=0.025];手术时间的延长不受PFC大小、部位和类型的影响。荧光透视并没有影响技术成功率,所有21例患者均成功置入ELAMS。相比荧光下操作,无荧光操作的临床缓解率(91%vs 71%,P=0.52)和影像缓解率(57%vs 71%,P=0.65)的差异均无统计学意义。无荧光操作患者中有3例出现了支架移位/误置。结论:囊肿胃吻合术中放置ELAMS无需荧光透视。无荧光操作可以显著缩短手术时间,而且并不影响技术成功率和临床成功率。

关键词： pancreatic-fluid collections electrocautery-enhanced coaxial lumen-apposing,self-expanding metal stent(ELAMS) fluoroscopy endoscopic ultrasound

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