4.8 Article

Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking

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NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27816-1

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资金

  1. National Natural Science Foundation of China [81972134, 82102535]
  2. National Key Research and Development Program of China [2018YFC1106200]
  3. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20171906]
  4. Shanghai Jiao Tong University Medical and Research Program [YG2021ZD06, ZH2018ZDA04]
  5. China Postdoctoral Science Foundation [2019M661560]
  6. GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine

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In this study, a dual-effect coating was designed to modulate the osteoimmune microenvironment and enhance bone regeneration. The coating, which immobilized immunomodulatory metal ions and osteoinductive growth factors, significantly increased the recruitment of M2 macrophages and upregulated the expression of M2 cytokines. This led to improved bone-implant mechanical fixation and new bone ingrowth.
Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn2+) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO2 group, Zn2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.

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