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Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis

Bioactive Materials 2023年第4期22卷 423-452页

作者： Zichang Liu Yu Zhuang Lianfei Fang Changyong Yuan Xudong Wang Kaili Lin Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China Shanghai Jiao Tong University School of Medicine Shanghai200025China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration(Tongji University) Ministry of Education389 Xincun Road200065 ShanghaiPR China School of Stomatology Xuzhou Medical UniversityDepartment of Dental ImplantThe Affiliated Stomatological Hospital of Xuzhou Medical UniversityXuzhouChina

Osteoarthritis(OA)is a highly prevalent whole-joint disease that causes disability and pain and affects a patient’s quality of life.However,currently,there is a lack of effective early diagnosis and treatment.Although stem cells can promote cartilage repair and treat OA,problems such as immune rejection and tumorigenicity persist.Extracellular vesicles(EVs)can transmit genetic information from donor cells and mediate intercellular communication,which is considered a functional paracrine factor of stem cells.Increasing evidences suggest that EVs may play an essential and complex role in the pathogenesis,diagnosis,and treatment of OA.Here,we introduced the role of EVs in OA progression by influencing inflammation,metabolism,and aging.Next,we discussed EVs from the blood,synovial fluid,and joint-related cells for diagnosis.Moreover,we outlined the potential of modified and unmodified EVs and their combination with biomaterials for OA therapy.Finally,we discuss the deficiencies and put forward the prospects and challenges related to the application of EVs in the field of OA.

关键词： Extracellular vesicles Osteoarthritis Biomarkers Diagnosis Treatment

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Nanoparticles modified by polydopamine: Working as “drug” carriers

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Bioactive Materials 2020年第3期5卷 522-541页

作者： Anting Jin Yitong Wang Kaili Lin lingyong Jiang Department of Oral&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 StomatologyShanghai200011PR China

Inspired by the mechanism of mussel adhesion,polydopamine(PDA),a versatile polymer for surface modification has been discovered.Owing to its unique properties like extraordinary adhesiveness,excellent biocompatibility,mild synthesis requirements,as well as distinctive drug loading approach,strong photothermal conversion capacity and reactive oxygen species(ROS)scavenging facility,various PDA-modified nanoparticles have been desired as drug carriers.These nanoparticles with diverse nanostructures are exploited in multifunctions,consisting of targeting,imaging,chemical treatment(CT),photodynamic therapy(PDT),photothermal therapy(PTT),tissue regeneration ability,therefore have attracted great attentions in plenty biomedical applications.Herein,recent progress of PDA-modified nanoparticle drug carriers in cancer therapy,antibiosis,prevention of inflammation,theranostics,vaccine delivery and adjuvant,tissue repair and implant materials are reviewed,including preparation of PDA-modified nanoparticle drug carriers with various nanostructures and their drug loading strategies,basic roles of PDA surface modification,etc.The advantages of PDA modification in overcoming the existing limitations of cancer therapy,antibiosis,tissue repair and the developing trends in the future of PDA-modified nanoparticle drug carriers are also discussed.

关键词： Surface modification Polydopamine Nanoparticles Drug carriers

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The development of collagen based composite scaffolds for bone regeneration

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Bioactive Materials 2018年第1期3卷 129-138页

作者： Dawei Zhang Xiaowei Wu Jingdi Chen Kaili Lin School&Hospital of Stomatology Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai 200072China Institute of Biomedical and Pharmaceutical Technology Fuzhou UniversityFuzhou 350002China

Bone is consisted of bone matrix,cells and bioactive factors,and bone matrix is the combination of inorganic minerals and organic polymers.Type I collagen fibril made of five triple-helical collagen chains is the main organic polymer in bone matrix.It plays an important role in the bone formation and remodeling process.Moreover,collagen is one of the most commonly used scaffold materials for bone tissue engineering due to its excellent biocompatibility and biodegradability.However,the low mechanical strength and osteoinductivity of collagen limit its wider applications in bone regeneration field.By incorporating different biomaterials,the properties such as porosity,structural stability,osteoinductivity,osteogenicity of collagen matrixes can be largely improved.This review summarizes and categorizes different kinds of biomaterials including bioceramic,carbon and polymer materials used as components to fabricate collagen based composite scaffolds for bone regeneration.Moreover,the possible directions of future research and development in this field are also proposed.

关键词： Collagen Bone regeneration Composite scaffolds Biomaterials Tissue engineering

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Estimating the number of Chinese cancer patients eligible for and benefit from immune checkpoint inhibitors

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Frontiers of Medicine 2022年第5期16卷 773-783页

作者： kaili Yang Jiarui Li lin Zhao Zhao Sun Chunmei Bai Department of Medical Oncology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100032China

The total number of cancer patients who are eligible for and will benefit from immune checkpoint inhibitors(ICIs)in China has not been quantified.This cross-sectional study was conducted to estimate the number of Chinese cancer patients with eligibility and response to ICIs based on the 2015 Chinese cancer statistics and the immune checkpoint inhibitor clinical practice guideline of the Chinese Society of Clinical Oncology.A total of 11 ICIs were recommended for 17 cancer types.The estimated number of eligible patients annually was 1290156(55.18%),which included 888738 males(60.05%)and 400468 females(46.67%).The estimated number of responders annually was 448972(19.20%),which included 309023 males(20.88%)and 139764 females(16.29%).Gastric cancer(n=291000,12.45%),non-small-cell lung cancer(n=289629,12.39%),and hepatocellular carcinoma(n=277100,11.85%)were the top three cancer types with the highest number of eligible patients.Non-small-cell lung cancer(n=180022,7.70%),hepatocellular carcinoma(n=75648,3.24%),and small-cell lung cancer(n=64362,2.75%)were the top three cancer types with the highest number of responders.In conclusion,ICIs provide considerable benefit in Chinese cancer patients under optimal estimation.

关键词： benefit China eligibility immune checkpoint inhibitor public health

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3D-printed surface promoting osteogenic differentiation and angiogenetic factor expression of BMSCs on Ti6Al4V implants and early osseointegration in vivo

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Journal of Materials Science & Technology 2019年第2期35卷 336-343页

作者： Jinkai Zhang Wenhui Zhou Hui Wang Kaili Lin Fengshan Chen Department of Orthodontics School & Hospital of Stomatology Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration Department of Oral & Cranio-Maxillofacial Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology

Three-dimensional-printed(3 D-P) titanium implants display many advantages, such as design flexibility,higher efficiency, the capability to easily construct complex or customized structures, etc., and is believed to potentially replace traditional implants. However, the biological performance of the 3 D-P titanium surface has not been investigated systematically. Herein, we analyzed the surface characteristics of 3 D-P Ti6 Al4 V implants and evaluated the biological responses of bone marrow derived mesenchymal stromal cells(BMSCs) to the 3 D-P surface in vitro. Moreover, after implantation into the rat femoral condyle for3 and 6 weeks, the osseointegration performance was evaluated. The results showed the 3 D-P Ti6 Al4 V implant presented distinct fluctuant macroscale rough surface and relatively better hydrophilicity which enhanced the adhesion, proliferation, osteogenic differentiation and angiogenetic factor expression of BMSCs. Moreover, the in vivo osseointegration performance was also better than that of the control group at the early stage. The present study suggested the 3 D-P titanium alloy is a promising candidate to be used as implant material.

关键词： Three-dimensional printing Titanium alloy BMSCs Osteogenesis Osseointegration

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Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration

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Bone Research 2022年第1期10卷 46-64页

作者： Hongpu Wei Jinjie Cui Kaili Lin Jing Xie Xudong Wang Department of Oral&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 StomatologyShanghai 200011China State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China

Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem,researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific p H reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration.Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.

关键词： biomaterials smart rational

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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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A comparative study of the osteogenic performance between the hierarchical micro/submicro-textured 3D-printed Ti6Al4V surface and the SLA surface

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Bioactive Materials 2020年第1期5卷 9-16页

作者： Jinkai Zhanga Jiaqiang Liu Chengtao Wang Fengshan Chen Xudong Wang Kaili Lin Department of Orthodontics School&Hospital of StomatologyTongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai200072China Department of Oral&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 of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai200240China

Three-dimensional(3D)printed titanium and its alloys have broad application prospect in the field of biomedical implant materials,although the biological performance of the original surface should be improved.Learning from the development experience of conventional titanium implants,to construct a hierarchical hybrid topological surface is the future direction of efforts.Since the original 3D-printed(3D hereafter)Ti6Al4V surface inherently has micron-scale features,in the present study,we introduced submicron-scale pits on the original surface by acid etching to obtain a hierarchical micro/submicro-textured surface.The characteristic and biological performance of the 3D-printed and acid-etched(3DA hereafter)surface were evaluated in vitro and in vivo,compared with the conventional sandblasted,large-grit,acid-etched(SLA hereafter)surface.Our results suggested the adhesion,proliferation and osteogenic differentiation of bone marrow derived mesenchymal stromal cells(BMSCs),as well as the in vivo osseointegration on 3DA surfaces were significantly improved.However,the overall osteogenic performance of the 3DA surface was not as good as the conventional SLA surface.

关键词： 3D printing Ti6Al4V Surface modification Osteogenesis SLA

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T-QoS-aware based parallel ant colony algorithm for services composition

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Journal of Systems Engineering and Electronics 2015年第5期26卷 1100-1106页

作者： lin Zhang kaili Rao Ruchuan Wang College of Computer Nanjing University of Posts and Telecommunications Institute of Computer Technology Nanjing University of Posts and Telecommunications Jiangsu High Technology Research Key Laboratory for Wireless Sensor Networks Key Lab of Broadband Wireless Communication and Sensor Network Technology Nangjing University of Posts and Telecommunications

In order to make cloud users get credible, high-quality composition of services, the trust quality of service aware(TQoS-aware) based parallel ant colony algorithm is proposed. Our approach takes the service credibility as the weight of the quality of service, then calculates the trust service quality T-QoS for each service, making the service composition situated in a credible environment. Through the establishment on a per-service T-QoS initialization pheromone matrix, we can reduce the colony’s initial search time. By modifying the pheromone updating rules and introducing two ant colonies to search from different angles in parallel,we can avoid falling into the local optimal solution, and quickly find the optimal combination of global solutions. Experiments show that our approach can combine high-quality services and the improvement of the operational success rate. Also, the convergence rate and the accuracy of optimal combination are improved.

关键词： services composition trust service quality ant colony algorithm parallel

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The effects of inactivated SARS-CoV-2 vaccination and subsequent infection of pregnant mice on the behaviors of offspring

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Animal Models and Experimental Medicine 2022年第5期5卷 430-435页

作者： Kaili Lin Meixuan Liu Lu Sun Hongwei Qiao Shunyi Wang Sidan Pan Hanjun Fu Jingzhu Wang Qiang Wei Hong Gao Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

The mass inoculation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019(COVID-19).Pregnant women are prone to a higher risk of COVID-19,and maternal infection is a risk fac-tor for a range of neurological disorders leading to abnormal behavior in adulthood.However,there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood.In this study,human angiotensin-converting enzyme 2 pregnant mice(F0 generation)were immunized with CoronaVac and then infected with SARS-CoV-2.Subsequently,we analyzed the behavioral cognition of their adult offspring(F1 gen-eration)using the open-field test and Morris water maze test.The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial refer-ence memory.

关键词： offspring spatial reference memory spontaneous locomotor activity

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