Restoration of electrical microenvironment enhances bone regeneration under diabetic conditions by modulating macrophage polarization

作     者：Xiaohan Dai Boon Chin Heng Yunyang Bai Fuping You Xiaowen Sun Yiping Li Zhangui Tang Mingming Xu Xuehui Zhang Xuliang Deng 

作者机构：Hunan Key Laboratory of Oral Health Research&Hunan 3D Printing Engineering Research Center of Oral Care&Hunan Clinical Research Center of Oral Major Diseases and Oral Health&Xiangya Stomatological Hospital&Xiangya School of StomatologyCentral South UniversityChangsha410008PR China Department of Dental Materials&Dental Medical Devices Testing CenterPeking University School and Hospital of StomatologyBeijing100081PR China Department of Geriatric DentistryPeking University School and Hospital of StomatologyBeijing100081PR China Central LaboratoryPeking University School and Hospital of StomatologyBeijing100081PR China Institute of Systems BiomedicineDepartment of ImmunologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University Health Science CenterBeijing100191PR China National Engineering Laboratory for Digital and Material Technology of StomatologyNMPA Key Laboratory for Dental MaterialsBeijing Laboratory of Biomedical Materials&Beijing Key Laboratory of Digital StomatologyPeking University School and Hospital of StomatologyBeijing100081PR China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2021年第6卷第7期

页      面：2029-2038页

核心收录：

学科分类：1002[医学-临床医学] 08[工学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 080502[工学-材料学] 10[医学] 

基　　金：This work was supported by the National Key R&D Program of China(2018YFC1105303/04) National Natural Science Foundation of China(Nos.51772006,31670993,51973004,81991505,82022016) Beijing Municipal Science&Technology Commission Projects(Z181100002018001) Peking University Medicine Fund(Nos.PKU2020LCXQ009,BMU2020PYB029) Natural Science Foundation of Hunan Province(2019JJ50779) Health and Family Planning Commission of Hunan Province(20180246) 

主　　题：Electrical microenvironment Diabetes Ferroelectric nanocomposites Bone regeneration Macrophage polarization 

摘      要：Macrophage-mediated inflammation compromises bone repair in diabetic *** signaling cues are known to regulate macrophage ***,the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be *** the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite *** vitro,the polarized BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite membranes inhibited high glucose-induced M1-type inflammation,by effecting changes in cell morphology,M1 marker expression and pro-inflammatory cytokine secretion in *** led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells(BM-MSCs).In vivo,the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory(M1)into the pro-healing(M2)phenotype,which in turn enhanced bone regeneration in rats with type 2 diabetes *** studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway,thereby inducing favorable osteo-immunomodulatory *** study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions,and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.