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Cited by 357

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

A Biomimetic Hierarchical Nanointerface Orchestrates Macrophage Polarization and Mesenchymal Stem Cell Recruitment To Promote Endogenous Bone Regeneration

Jin, Shan-Shan, He, Dan-Qing, Luo, Dan, Wang, Yu, Yu, Min, Guan, Bo, Fu, Yu, Li, Zi-Xin, Zhang, Ting, Zhou, Yan-Heng, Wang, Cun-Yu, Liu, Yan·2019·ACS Nano

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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Crossref · 10.1021/acsnano.9b00489

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Metadata

Authors
Jin, S.-S., He, D.-Q., Luo, D., Wang, Y., Yu, M., Guan, B., Fu, Y., Li, Z.-X., Zhang, T., Zhou, Y.-H., Wang, C.-Y., & Liu, Y.
Venue
ACS Nano
Published
2019-05-24
Volume
13
Issue
6
Pages
6581-6595
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
OpenAlex
W2945703177
Cited by
357
References
48
FWCI
12.69
Type
journal article
Language
en
Open access
closed

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