| Title | A Biomimetic Hierarchical Nanointerface Orchestrates Macrophage Polarization and Mesenchymal Stem Cell Recruitment To Promote Endogenous Bone Regeneration |
| Authors | 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 |
| Affiliation | Peking Univ, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing Key Lab Digital Stomatol,Dept Orthodont, Lab Biomimet Nanomat,Sch & Hosp Stomatol, Beijing 100081, Peoples R China China Univ Petr, Inst New Energy, Beijing 102249, Peoples R China Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China Peking Univ, Hosp Stomatol, Div 4, Beijing 100025, Peoples R China Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Lab Mol Signaling, Los Angeles, CA 90095 USA |
| Keywords | biomimetic nanointerface osteoimmunomodulation macrophage mesenchymal stem cells interleukin-4 endogenous bone regeneration |
| Issue Date | 2019 |
| Publisher | ACS NANO |
| Abstract | The host immune response to bone bio-materials 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(+)CDI63(+) 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. |
| URI | http://hdl.handle.net/20.500.11897/547712 |
| ISSN | 1936-0851 |
| DOI | 10.1021/acsnano.9b00489 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 口腔医院 |
