A Biomimetic Hierarchical Nanointerface Orchestrates Macrophage Polarization and Mesenchymal Stem Cell Recruitment To Promote Endogenous Bone RegenerationClick to copy article linkArticle link copied!
- Shan-Shan JinShan-Shan JinLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Shan-Shan Jin
- Dan-Qing HeDan-Qing HeLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Dan-Qing He
- Dan LuoDan LuoInstitute of New Energy, China University of Petroleum (Beijing), Beijing 102249, ChinaMore by Dan Luo
- Yu WangYu WangLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Yu Wang
- Min YuMin YuLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Min Yu
- Bo GuanBo GuanBeijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaMore by Bo Guan
- Yu Fu
- Zi-Xin LiZi-Xin LiLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Zi-Xin Li
- Ting ZhangTing ZhangLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Ting Zhang
- Yan-Heng ZhouYan-Heng ZhouLaboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Yan-Heng Zhou
- Cun-Yu WangCun-Yu WangLaboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles, Los Angeles, California 90095, United StatesMore by Cun-Yu Wang
- Yan Liu*Yan Liu*E-mail: [email protected]Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, ChinaMore by Yan Liu
Abstract
The host immune response to bone biomaterials is vital in determining scaffold fates and bone regeneration outcomes. The nanometer-scale interface of biomaterials, which independently controls physical inputs to cells, regulates osteogenic differentiation of stem cells and local immune response. Herein, we fabricated biomimetic hierarchical intrafibrillarly mineralized collagen (HIMC) with a bone-like staggered nanointerface and investigated its immunomodulatory properties and mesenchymal stem cell (MSC) recruitment during endogenous bone regeneration. The acquired HIMC potently induced neo-bone formation by promoting CD68+CD163+ M2 macrophage polarization and CD146+STRO-1+ host MSC recruitment in critical-sized bone defects. Mechanistically, HIMC facilitated M2 macrophage polarization and interleukin (IL)-4 secretion to promote MSC osteogenic differentiation. An anti-IL4 neutralizing antibody significantly reduced M2 macrophage-mediated osteogenic differentiation of MSCs. Moreover, HIMC-loaded-IL-4 implantation into critical-sized mandible defects dramatically enhanced bone regeneration and CD68+CD163+ M2 macrophage polarization. The depletion of monocyte/macrophages by clodronate liposomes significantly impaired bone regeneration by HIMC, but did not affect MSC recruitment. Thus, in emulating natural design, the hierarchical nanointerface possesses the capacity to recruit host MSCs and promote endogenous bone regeneration by immunomodulation of macrophage polarization through IL-4.
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