Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics

Mingzheng Li, Xiaodong Guo, Wenting Qi, Zhenzhen Wu, Joost D. De Bruijn, Yu Xiao*, Chongyun Bao*, Huipin Yuan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)

Abstract

To investigate the roles of macrophages in material-instructed bone formation, two calcium phosphate (TCP) ceramics with the same chemistry but various scales of surface topography were employed in this study. After being implanted subcutaneously in FVB mice for 8 weeks, TCPs (TCP ceramics with submicron surface topography) gave rise to bone formation, while TCPb (TCP ceramics with micron surface topography) did not, showing the crucial role of surface topography scale in material-instructed bone formation. Depletion of macrophages with liposomal clodronate (LipClod) blocked such bone formation instructed by TCPs, confirming the role of macrophages in material-instructed bone formation. Macrophage cells (i.e. RAW 264.7 cells) cultured on TCPs in vitro polarized to tissue repair macrophages as evidenced by gene expression and cytokine production, while polarizing to pro-inflammatory macrophages on TCPb. Submicron surface topography of TCP ceramics directed macrophage polarization via PI3K/AKT pathways with the synergistic regulation of integrin beta 1. Finally, the tissue repair macrophage polarization on TCPs resulted in osteogenic differentiation of mesenchymal stem cells in vitro. At early implantation in FVB mice, TCPs recruited more macrophages which polarized towards tissue repair macrophages with time. The present data demonstrate the important roles of macrophage polarization in bone formation instructed by calcium phosphate ceramics.

Original languageEnglish
Pages (from-to)1863-1877
Number of pages15
JournalJournal of Materials Chemistry. B, Materials for Biology and Medicine
Volume8
Issue number9
DOIs
Publication statusPublished - 7 Mar 2020

Keywords

  • BETA-TRICALCIUM PHOSPHATE
  • GROWTH-FACTOR 1
  • STEM-CELLS
  • OSTEOGENIC DIFFERENTIATION
  • OSTEOINDUCTIVE BIOMATERIALS
  • TISSUE-REPAIR
  • SURFACE
  • PROLIFERATION
  • PHENOTYPE
  • CHEMISTRY

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