Inflammatory and differentiation cellular response to calcium silicate cements: An in vitro study

Int Endod J. 2023 May;56(5):593-607. doi: 10.1111/iej.13894. Epub 2023 Feb 8.

Abstract

Aim: Inflammatory-regenerative cell interaction is believed to mediate hard tissue formation. This study aimed to investigate the interaction between human inflammatory monocytes with human regenerative fibroblasts after exposure to different calcium silicate materials.

Methodology: Human monocytes were cultured on three materials, polystyrene (PS), mineral trioxide aggregates (MTA) and biodentine (BD), in the presence or absence of lipopolysaccharide (LPS). Half of the monocyte-conditioned media (MoCM) of each group was used to analyse inflammatory cytokine secretion, namely TNF-α, IL-1β, IL-1RA and IL-6. The remaining MoCM was used to culture recipient fibroblasts, measuring the cell number (proliferation) and levels of alkaline phosphatase (differentiation) and lactic acid dehydrogenase (cytotoxicity).

Results: In absence of LPS, MTA was associated with higher secretion of TNF-α and lower secretion of IL-1β, while BD triggered higher secretions of both cytokines when both materials were compared to control (PS). When LPS was added, higher levels of all analysed cytokines were observed in the PS and BD groups, whereas for the MTA group, only TNF-α and IL-6 were increased. Fibroblasts responded differently to the MoCM from the different groups, revealing significant increases in proliferation and differentiation capacities, particularly when cultured in CM from monocytes exposed to MTA. The morphological evaluation revealed different patterns of fibroblast shape and spread in the different MoCM groups.

Conclusion: Calcium silicate materials modulate the monocyte inflammatory response, which subsequently induce differential effects on the recipient fibroblasts. MTA appears to promote the secretion of prodifferentiation signals from the monocytes, which are received by fibroblasts, promoting their proliferation and differentiation. The model represents a promising tool to evaluate the interaction of different cells in response to different materials.

Keywords: calcium silicate cements; cell communication; fibroblast; inflammation; monocytes; regeneration.

MeSH terms

  • Aluminum Compounds / pharmacology
  • Calcium Compounds / pharmacology
  • Cell Differentiation
  • Cytokines
  • Drug Combinations
  • Humans
  • Interleukin-6*
  • Lipopolysaccharides / pharmacology
  • Oxides / pharmacology
  • Silicates / pharmacology
  • Tumor Necrosis Factor-alpha*

Substances

  • calcium silicate
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Lipopolysaccharides
  • tricalcium silicate
  • Calcium Compounds
  • Silicates
  • Cytokines
  • Oxides
  • Drug Combinations
  • Aluminum Compounds