In vitro biological response of human osteoblasts in 3D chitosan sponges with controlled degree of deacetylation and molecular weight

Carbohydr Polym. 2021 Feb 15:254:117434. doi: 10.1016/j.carbpol.2020.117434. Epub 2020 Nov 22.

Abstract

We have studied the effect of chitosan sponges, produced from chitosan batches with distinct degree of deacetylation (DDA) and molecular weight (Mw), on the adhesion, growth and differentiation of primary human osteoblasts with an aim to offer a suitable tool for guided bone regeneration. All the chitosan sponges revealed similar microstructure, irrespective of the DDA (58, 73, 82, 88, and 91 %) and Mw (749, 547, 263, 215, and 170 kDa, respectively). Cell spreading was higher on sponges having a higher DDA. Higher DDA induced a more pronounced increase in alkaline phosphatase activity, osteopontin (OPN), vascular endothelial growth factor-A (VEGF), interleukin-6 (IL-6), and reduction in monocyte chemoattractant protein-1 (MCP-1), sclerostin (SOST) and dickkopf related protein-1 as compared to lower DDA. Lower DDA induced the increased secretion of osteoprotegerin and SOST as compared to higher DDA. The combination of higher DDA and Mw induced an increased secretion of VEGF and IL-6, however reduced the secretion of OPN as compared to chitosan with similar DDA but with lower Mw. In summary, the variations in cellular responses to the different chitosan sponges indicate a potential for individual tailoring of desired responses in guided bone regeneration.

Keywords: Chitosan; Degree of deacetylation; Molecular weight; Osteoblasts.

MeSH terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Biomarkers / metabolism
  • Bone Regeneration
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacology*
  • Gene Expression / drug effects*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Models, Biological
  • Molecular Structure
  • Molecular Weight
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism
  • Primary Cell Culture
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • DKK1 protein, human
  • Delayed-Action Preparations
  • IL6 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-6
  • Osteoprotegerin
  • SOST protein, human
  • SPP1 protein, human
  • TNFRSF11B protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Osteopontin
  • Chitosan
  • Alkaline Phosphatase