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

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

Bioactive Materials (Jul 2021)

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

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

Affiliations

Xiaohan Dai: 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 Stomatology, Central South University, Changsha, 410008, PR China; Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
Boon Chin Heng: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
Yunyang Bai: Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
Fuping You: Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, 100191, PR China
Xiaowen Sun: Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China
Yiping Li: 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 Stomatology, Central South University, Changsha, 410008, PR China
Zhangui Tang: 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 Stomatology, Central South University, Changsha, 410008, PR China
Mingming Xu: Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; Corresponding author. Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
Xuehui Zhang: Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; National Engineering Laboratory for Digital and Material Technology of Stomatology, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; Corresponding author. Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
Xuliang Deng: Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; National Engineering Laboratory for Digital and Material Technology of Stomatology, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; Corresponding author. Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.

Journal volume & issue: Vol. 6, no. 7
pp. 2029 – 2038

Abstract

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Macrophage-mediated inflammation compromises bone repair in diabetic patients. Electrical signaling cues are known to regulate macrophage functions. However, the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated. Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membrane. In vitro, the polarized BaTiO3/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 macrophages. This 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 mellitus. Mechanistic 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 effects. Our 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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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