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Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment

Bioactive materials 2023年第1期19卷 474-485页

作者： Cuidi Li Changwei Li zhenjiang ma Hongfang Chen Huitong Ruan Lianfu Deng Jinwu Wang Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025PR China Shanghai Key Laboratory of Orthopedic Implant Department of Orthopedic SurgeryShanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of MedicineShanghai200011PR China

The 3D printing technique is suitable for patient-specific implant preparation for bone repair after bone tumor ***,improving the survival rate due to tumor recurrence remains a challenge for *** macrophage polarization induction to M2-type tumor-associated macrophages(TAMs)by the tumor microenvironment is a key factor of immunosuppression and tumor *** this study,a regenerative scaffold regulating the macrophage immune microenvironment and promoting bone regeneration in a dual-stage process for the postoperative treatment of bone tumors was constructed by binding a colony-stimulating factor 1 receptor(CSF-1R)inhibitor GW2580 onto in situ cosslinked hydroxybutylchitosan(HBC)/oxidized chondroitin sulfate(OCS)hydrogel layer covering a 3D printed calcium phosphate scaffold based on electrostatic *** hydrogel layer on scaffold surface not only supplied abundant sulfonic acid groups for stable loading of the inhibitor,but also acted as the cover mask protecting the bone repair part from exposure to unhealthy growth factors in the microenvironment at the early treatment *** local prolonged release of inhibitor being realized via the functional material design,CSF-1R,the main pathway that induces polarization of TAMs,can be efficiently blocked,thus regulating the immunosuppressive microenvironment and inhibiting tumor development at a low therapeutic *** the later stage of treatment,calcium phosphate component of the scaffold can facilitate the repair of bone defects caused by tumor *** conclusion,the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment.

关键词： 3D printing Drug delivery Microenvironment macrophage polarization Bone regeneration

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3D-Printed Scaffolds Promote Angiogenesis by Recruiting Antigen-Specific T Cells

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Engineering 2022年第10期17卷 183-195页

作者： Cuidi Li zhenjiang ma Wentao Li Tianyang Jie Liping Zhong Hongfang Chen Wenhao Wang Jinwu Wang Wenguo Cui Yongxiang Zhao Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Orthopedic Surgery Shanghai Key Laboratory of Orthopedic ImplantsShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China National Center for International Research of Bio-targeting Theranostics Guangxi Key Laboratory of Bio-targeting TheranosticsCollaborative Innovation Center for Targeting Tumor TheranosticsGuangxi Medical UniversityNanning 530021China

The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed ***,scaffolds that can subtly regulate immune responses may display extraordinary *** by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response *** the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early *** silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being *** room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)*** release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine *** vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in *** embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the ***,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized *** method may provide a novel concept for patient-specific implant design for angiogenesis promotion.

关键词： 3D printing Immune microenvironment regulating Angiogenesis Bone regeneration

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Lenke5型青少年特发性脊柱侧凸腰椎与骨盆参数的相关性

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中国组织工程研究 2024年第36期28卷 5753-5758页

作者：侯俞彤黄承兰杨云霄李娅郭培武于文强赵宇王赞博曾红马振江鲁德志王金武潍坊医学院康复医学院山东省潍坊市261053 潍坊市人民医院康复科山东省潍坊市261053 浙江大学医学院附属第一医院康复科浙江省杭州市310003 上海交通大学转化医学研究院上海市201100 上海交通大学医学院附属第九人民医院康复科上海市200011 上海交通大学医学院附属第九人民医院骨科上海市200011

背景:目前对于Lenke5型主腰弯脊柱侧凸患者腰椎与骨盆的研究仅局限于冠状面及矢状面,尚未明确侧弯与骨盆间的三维关系。目的:分析Lenke5型主腰弯脊柱侧凸患者腰椎侧弯对骨盆的影响,研究腰椎与骨盆三维空间位置的相关性。方法:回顾性分... 详细信息

背景:目前对于Lenke5型主腰弯脊柱侧凸患者腰椎与骨盆的研究仅局限于冠状面及矢状面,尚未明确侧弯与骨盆间的三维关系。目的:分析Lenke5型主腰弯脊柱侧凸患者腰椎侧弯对骨盆的影响,研究腰椎与骨盆三维空间位置的相关性。方法:回顾性分析上海交通大学医学院附属第九人民医院3D打印接诊中心2019年1月至2023年9月收治的60例Lenke5型主腰弯脊柱侧凸患者的影像学数据,包括Cobb角、冠状骨盆倾斜、腰椎前凸角、左右骨盆髋骨宽度比值、脊柱旋转角度、骨盆倾斜、骶骨斜率、骨盆入射角、冠状畸形角比率、矢状畸形角比率、C7铅垂线与骶骨中垂线的距离、椎体顶点平移、冠状骶骨倾角,将信息汇总为数据库,运用SPSS 22.0软件采用Spearman相关性分析和线性回归分析Lenke5型主腰弯青少年特发性脊柱侧凸患者腰椎与骨盆的相关数据。结果与结论:①Cobb角与冠状畸形角比率、椎体顶点平移距离、脊柱旋转角度呈高度正相关关系(r=0.91,r=0.841,r=0.736);②冠状畸形角比率与椎体顶点平移距离呈高度正相关关系(r=0.737),与C7铅垂线到骶骨中垂线的距离呈中度正相关关系(r=0.514),与矢状畸形角比率呈中度负相关关系(r=-0.595);③腰椎前凸角与矢状畸形角比率呈高度正相关关系(r=0.942),与冠状畸形角比率呈中度负相关关系(r=-0.554);④Cobb角与冠状骨盆倾斜角、冠状骶骨倾角呈中度正相关关系(r=0.522,r=0.534),C7铅垂线到骶骨中垂线的距离与冠状骨盆倾斜角呈中度正相关关系(r=0.507);椎体顶点平移距离与冠状骨盆倾斜角、冠状骶骨倾角呈中度正相关关系(r=0.507,r=0.506),腰椎前凸角与骶骨斜率、骨盆入射角呈中度正相关关系(r=0.512,r=0.538);矢状畸形角比率与骶骨斜率、骨盆入射角呈中度正相关关系(r=0.614,r=0.621);⑤结果发现腰椎与骨盆相对位置在水平面、矢状面、冠状面上息息相关,当腰椎出现侧凸、旋转时,骨盆的相对位置也会变化进行代偿,这表明矫正脊柱侧凸的同时,也不能忽略骨盆的矫正。

关键词：青少年特发性脊柱侧凸 Lenke5型腰椎骨盆三维评估相关性

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Zwitterionic ring-opening polymerization of macrocyclic ethyleneoxy-substituted carbonate:Access to cyclic PEG-like polycarbonate

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Chinese Chemical Letters 2024年第3期35卷 282-286页

作者： Jin Huang Jinwen Li Rui Yan Yuanyuan Qu Fengzhen Guo Lei Shen Can-liang ma Jie Sun zhenjiang Li Kai Guo State Key Laboratory of materials-Oriented Chemical Engineering College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjing 211816China Institute of Nanjing Advanced Biomaterials&Processing Equipment Lishui Economic Development ZoneNanjing 211299China

The innovation in polymer design to rival conventional polyethylene glycol(PEG)is an important approach to achieving a more sustainable ***,cyclic PEG-like polycarbonates having high molecular weight(4.4–49.5 kg/mol)were enabled through zwitterionic ring-opening polymerization(ZROP)of macrocyclic carbonates(MCs)mediated by N-heterocyclic carbene(NHC).The thermodynamic behavior of polymerization depends on the ring size of *** this process,the ZROP of 11-membered MC was driven by the change of enthalpy(ΔH_(p))which differed from the ZROP of 14-membered MC driven by the entropic change(ΔS_(p)).Cyclic polycarbonates depicted improved thermostability(T_(d5%)≥204℃)and higher glass transition temperatures(T_(g)>–40℃)in comparison to their linear analogues(T_(d5%)≤185℃,T_(g)~–50℃).In addition,the mechanism of ZROP of MC was addressed through computational study.A distinct mechanism of polymerization distinguishable from the well-known NHC-mediated ZROP of cyclic esters was revealed,where the zwitterion from nucleophilic addition to MC,*** intermediate,cannot be ring-opened probably due to the delocalization of negative charge on the carbonate group,but serves as an active center for the *** comparison to PEG,the attained polymer demonstrated comparable hydrophilic and biocompatible properties,as revealed by the results of contact angle and in vitro cytotoxicity studies,suggesting that cyclic polycarbonate hold the promise as the alternative of PEG.

关键词： Zwitterionic ring-opening polymerization Cyclic polycarbonate macrocycles Tetrahedral intermediate NHC carbene

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Bioprinted constructs that simulate nerve-bone crosstalk to improve microenvironment for bone repair

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Bioactive materials 2023年第9期27卷 377-393页

作者： Tianchang Wang Wentao Li Yuxin Zhang Xiang Xu Lei Qiang Weiqiang Miao Xiaokun Yue Xin Jiao Xianhao Zhou zhenjiang ma Shuai Li Muliang Ding Junfeng Zhu Chi Yang Hui Wang Tao Li Xin Sun Jinwu Wang Shanghai Key Laboratory of Orthopedic Implant Department of Orthopedic SurgeryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineNo.639 Zhizaoju RoadShanghai200011China Sports Medicine Department Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalNo.49North Garden RoadHaidian DistrictBeijing100191China Peking University Institute of Sports Medicine No.49North Garden RoadHaidian DistrictBeijing100191China Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai200011China School of materials Science and Engineering Southwest Jiaotong UniversityChengdu610031China Department of Orthopedics The First Affiliated HospitalZhejiang University School of Medicine79 Qingchun RdHangzhou310003China Department of Orthopaedics The Second Xiangya HospitalCentral South UniversityChangsha410001HunanChina Institute of Rehabilitation Medicine School of Rehabilitation ScienceShanghai University of Traditional Chinese MedicineEngineering Research Center of Traditional Chinese Medicine Intelligent RehabilitationMinistry of EducationShanghai201210China Department of Orthopedic Surgery Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadShanghai200092China

Crosstalk between nerves and bone is essential for bone repair,for which Schwann cells(SCs)are crucial in the regulation of the *** that exosomes are critical paracrine mediators for intercellular communication that exert important effects in tissue repair,the aim of this study is to confirm the function and molecular mechanisms of Schwann cell-derived exosomes(SC-exos)on bone regeneration and to propose engineered constructs that simulate SC-mediated nerve-bone *** promoted the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs)through *** molecular mechanism studies demonstrated that SC-exos promoted BMSC osteogenesis by regulating the TGF-βsignaling pathway via ***,SC-exos promoted the migration and tube formation performance of endothelial progenitor ***,the SC-exos@G/S constructs were developed by bioprinting technology that simulated SC-mediated nerve-bone crosstalk and improved the bone regeneration microenvironment by releasing SC-exos,exerting the regulatory effect of SCs in the microenvironment to promote innervation,vascularization,and osteogenesis and thus effectively improving bone repair in a cranial defect *** study demonstrates the important role and underlying mechanism of SCs in regulating bone regeneration through SC-exos and provides a new engineered strategy for bone repair.

关键词： Schwann cells Microenvironment Nerve-bone crosstalk Exosomes Bioprinting

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Defects and morphology engineering for constructing V_(s)-Ni_(3)S_(2)@V_(s)-Cu_(2)S nanotube heterojunction arrays toward efficient bifunctional electrocatalyst for overall water splitting

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Journal of Energy Chemistry 2024年第7期94卷 29-40页

作者： Wenyuan Sun Alan Meng Lei Wang Guicun Li Jinfeng Cui Yongkai Sun zhenjiang Li College of materials Science and Engineering Qingdao University of Science and TechnologyQingdao 266042ShandongChina Key Laboratory of Optic-electric Sensing and Analytical Chemistryfor Life Science MOE College of Chemistry and Molecular EngineeringQingdao Universityof Science and TechnologyQingdao 266042ShandongChina College of Environment and Safety Engineering Qingdao University of Science and TechnologyQingdao 266042ShandongChina Qingdao Huanghai University Qingdao 266000ShandongChina College of Electromechanical Engineering Qingdao University of Science and TechnologyQingdao 266061ShandongChina

The development of highly active,stable and inexpensive electrocatalysts for hydrogen production by defects and morphology engineering remains a great ***,S vacancies-rich Ni_(3)S_(2)@Cu_(2)S nan-otube heterojunction arrays were in-situ grown on copper foam(V_(s)-Ni_(3)S_(2)@V_(s)-Cu_(2)S NHAs/CF)for efficient electrocatalytic overall water *** the merits of nanotube arrays and efficient electronic mod-ulation drived by the OD vacancy defect and 2D heterojunction defect,the resultant V_(s)-Ni_(3)S_(2)@V_(s)-Cu_(2)S NHAs/CF electrocatalyst exhibits excellent electrocatalytic activity with a low overpotential of 47 mV for the hydrogen evolution reaction(HER)at 10 ma cm^(-2) current density,and 263 mV for the oxygen evolution reaction(OER)at 50 ma cm^(-2) current density,as well as a cell voltage of 1.48 V at 10 ma cm^(-2).Moreover,the nanotube heterojunction arrays endows V_(s)-Ni_(3)S_(2)@V_(s)-Cu_(2)S NHAs/CF with outstanding stability in long-term catalytic processes,as confirmed by the continuous chronopotentiom-etry tests at current densities of 10 ma cm^(-2) for 100 h.

关键词： Nanotubearrays Heterojunction Vacancy Bifunctional electrocatalyst Overall water splitting

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Research Center of 3D Bioprinting in Shanghai Ninth People’s Hospital

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Bio-Design and manufacturing 2019年第3期2卷 213-220页

作者： Tao Li Xiaojun Zhou Changxu Deng Xiaoxiao Yang Han Yang zhenjiang ma Lan Cao Zezheng Yang Lei Qiang Jinwu Wang Kerong Dai Shanghai Key Laboratory of Orthopaedic Implant Department of Orthopaedic SurgeryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RdShanghai 200011China Med-X Research Institute School of Biomedical EngineeringShanghai Jiao Tong University1804 Huashan RdShanghai 200030China

The center was first established in 2013 and affiliated to the Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of *** 2015,the center was entitled as 3D Bioprinting Clinical Transformation Collaborative Innovation *** 2016,the center was renamed as Medical 3D Printing Innovation Research Center of Shanghai Jiao Tong University School of *** the center was established in 2013,the clinical application of 3D printing in Shanghai Ninth People’s Hospital can be traced back to the *** early as 30 years ago,*** Dai had tried to rebuild patients pelvic by manually cutting the foam boards and layering them together based on the theory of 3D printing for preoperative planning model of abnormal skeleton structures and development of personalized *** was the first application of 3D printing in the area of medicine in ***,The Research Center of 3D Bioprinting in Shanghai Ninth People’s Hospital comprised of subcenters including the outpatient department of 3D printing,medical 3D printing innovation research center and Shanghai key laboratory of orthopedic implant.

关键词： printing Transformation centers

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Correction:Incorporating mesopelagic fish into the evaluation of marine protected areas under climate change scenarios

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marine Life Science & Technology 2024年第2期6卷 363-364页

作者： Shuhao Liu Yang Liu Katharina Teschke mark A.Hindell Rachel Downey Briannyn Woods Bin Kang Shuyang ma Chi Zhang Jianchao Li zhenjiang Ye Peng Sun Jianfeng He Yongjun Tian Research Centre for Deep Sea and Polar Fisheries and Key Laboratory of MaricultureMinistry of EducationOcean University of ChinaQingdao 266003China Frontiers Science Center for Deep Ocean Multispheres and Earth System Ocean University of ChinaQingdao 266100China Alfred Wegener Institute Helmholtz Centre for Polar and Marine ResearchAm Handelshafen 1227570 BremerhavenGermany Helmholtz Institute for Functional marine Biodiversity at the University Oldenburg Ammerländer Heerstraße 23123129 OldenburgGermany Institute for marine and Antarctic Studies University of TasmaniaHobart 7004Australia Fenner School of Environment and Society Australian National UniversityCanberraACT 2602Australia College of Fisheries Ocean University of ChinaQingdao 266003China Polar Research Institute of China Shanghai 200136China

The author wants to highlight the important role of mes-opelagic fish in the conservation of marine living ***,in order to further clarify and focus research point on the conservation of marine living resources,the authors replaced the MPA with the protected areas,and slightly modified several other vague *** these corrections,most of them are the replacement of the terms.

关键词： protected correction fish

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Stable multi-electron reaction stimulated by W doping VS_(4)for enhancing magnesium storage performance

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Journal of Energy Chemistry 2024年第2期89卷 89-98,I0004页

作者： Yuxin Tian Jiankang Chen Guofeng Wang Bing Sun Alan Meng Lei Wang Guicun Li Jianfeng Huang Shiqi Ding zhenjiang Li College of materials Science and Engineering Qingdao University of Science and TechnologyQingdao 266042ShandongChina Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science MOEShandong Key Laboratory of Biochemical AnalysisCollege of Chemistry and Molecular EngineeringQingdao University of Science and TechnologyQingdao 266042ShandongChina School of material Science and Engineering International S&T Cooperation Foundation of Shaanxi ProvinceXi’an Key Laboratory of Green Manufacture of Ceramic MaterialsShaanxi University of Science and TechnologyXi’an 710021ShaanxiChina

Rechargeable magnesium batteries(RMBs)hold promise for offering higher volumetric energy density and safety features,attracting increasing research interest as the next post lithium-ion *** high performance cathode material by inducing multi-electron reaction process as well as maintaining structural stability is the key to the development and application of ***,multielectron reaction occurred in VS_(4)by simple W doping strategy.W doping induces valence of partial V as V^(2+)and V^(3+)in VS_(4)structure,and then stimulates electrochemical reaction involving multi-electrons in 0.5%*** flower-like microsphere morphology as well as rich S vacancies is also modulated by W doping to neutralize structure change in such multi-electron reaction *** fabricated 0.5%W-V-S delivers higher specific capacity(149.3 m A h g^(-1)at 50 m A g^(-1),which is 1.6 times higher than that of VS_(4)),superior rate capability(76 ma h g^(-1)at 1000 ma g^(-1)),and stable cycling performance(1500cycles with capacity retention ratio of 93.8%).Besides that,pesudocapaticance-like contribution analysis as well as galvanostatic intermittent titration technique(GITT)further confirms the enhanced Mg^(2+)storage kinetics during such multi-electron involved electrochemical reaction *** discovery provides new insights into the designing of multi-electron reaction process in cathode as well as neutralizing structural change during such reaction for realizing superior electrochemical performance in energy storage devices.

关键词： Multi-electron reaction W doping Stable structure Cathode Rechargeable magnesium batteries

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Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

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Bioactive materials 2021年第3期6卷 757-769页

作者： Xin Sun zhenjiang ma Xue Zhao Wenjie Jin Chenyu Zhang Jie ma Lei Qiang Wenhao Wang Qian Deng Han Yang Jinzhong Zhao Qianqian Liang Xiaojun Zhou Tao Li Jinwu Wang Shanghai Key Laboratory of Orthopaedic Implants Department of Orthopaedic SurgeryShanghai Ninth People's HospitalShanghai JiaoTong University School of MedicineNo.639 Zhizaoju RoadShanghai200011China Department of Radiology Shanghai Ninth People's HospitalShanghai JiaoTong University School of MedicineNo.639 Zhizaoju RoadShanghai200011China Department of Radiology Minhang Hospital of Fudan UniversityMinhang Central HospitalNo.170 Xinsong RoadShanghai 201100China Southwest JiaoTong University College of Medicine No.111 North 1st Section of Second Ring RoadChengdu610031China School of Biomedical Engineering Shanghai JiaoTong UniversityNo.1956 Huashan RoadShanghai200030China Department of Sports Medicine Shanghai Jiao Tong University Affiliated Sixth People's HospitalNo.600Yishan RoadShanghai 200233China Spine Institute Shanghai University of Traditional Chinese MedicineNo.1200 Cailun RoadShanghai 200032China College of Chemistry Chemical Engineering and BiotechnologyDonghua UniversityNo.2999North Renmin RoadShanghai 201620China Department of Orthopaedics Xinhua Hospital affiliated to Shanghai Jiaotong University School of MedicineNo.1665 Kongjiang RoadShanghai200092China

Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect ***-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone ***,we used modified bioinks comprising gelatin,gelatin methacryloyl(Gelma),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of Gelma/gelatin/PEG ***,MSNs sustainably released BMP-4 for long-term *** 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory ***-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted ***,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory *** 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone *** conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.

关键词： Three-dimensional bioprinting Diabetic bone defect Bone morphogenic protein-4 macrophage polarization Bone regeneration

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