Combining Calcium Phosphates with Polysaccharides: A Bone-Inspired Material Modulating Monocyte/Macrophage Early Inflammatory Response

Int J Mol Sci. 2018 Nov 3;19(11):3458. doi: 10.3390/ijms19113458.

Abstract

The use of inorganic calcium/phosphate supplemented with biopolymers has drawn lots of attention in bone regenerative medicine. While inflammation is required for bone healing, its exacerbation alters tissue regeneration/implants integration. Inspired by bone composition, a friendly automated spray-assisted system was used to build bioactive and osteoinductive calcium phosphate/chitosan/hyaluronic acid substrate (CaP-CHI-HA). Exposing monocytes to CaP-CHI-HA resulted in a secretion of pro-healing VEGF and TGF-β growth factors, TNF-α, MCP-1, IL-6 and IL-8 pro-inflammatory mediators but also IL-10 anti-inflammatory cytokine along with an inflammatory index below 1.5 (versus 2.5 and 7.5 following CaP and LPS stimulation, respectively). Although CD44 hyaluronic acid receptor seems not to be involved in the inflammatory regulation, results suggest a potential role of chemical composition and calcium release from build-up substrates, in affecting the intracellular expression of a calcium-sensing receptor. Herein, our findings indicate a great potential of CaP-CHI-HA in providing required inflammation-healing balance, favorable for bone healing/regeneration.

Keywords: bone inspired material; bone regeneration; cytotoxicity; inflammation; monocyte.

MeSH terms

  • Bone Regeneration / genetics
  • Bone Regeneration / immunology
  • Bone Substitutes / chemistry
  • Bone Substitutes / pharmacology*
  • Bone and Bones / cytology
  • Bone and Bones / metabolism
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / pharmacology*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Inflammation
  • Interleukins / genetics
  • Interleukins / immunology
  • Mitochondria / drug effects
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Calcium-Sensing / immunology
  • Signal Transduction
  • THP-1 Cells
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology
  • Vinculin / genetics
  • Vinculin / immunology

Substances

  • Bone Substitutes
  • CASR protein, human
  • CCL2 protein, human
  • CD44 protein, human
  • Calcium Phosphates
  • Chemokine CCL2
  • Hyaluronan Receptors
  • Interleukins
  • Reactive Oxygen Species
  • Receptors, Calcium-Sensing
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • VCL protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vinculin
  • Hyaluronic Acid
  • Chitosan
  • calcium phosphate