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

Nat Commun. 2022 Jan 10;13(1):160. doi: 10.1038/s41467-021-27816-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Biomarkers / metabolism
  • Bivalvia / chemistry
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone-Implant Interface / growth & development*
  • Cell Differentiation / drug effects
  • Femur / cytology
  • Femur / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / immunology
  • Osteogenesis / drug effects
  • Prostheses and Implants
  • Protein Precursors / pharmacology
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Titanium / pharmacology*
  • Zinc / pharmacology*

Substances

  • Antigens, CD
  • Biomarkers
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Lipopolysaccharides
  • Protein Precursors
  • bioadhesive precursor protein, Mytilus
  • Interleukin-10
  • titanium dioxide
  • Titanium
  • Zinc