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Transcriptomic Analysis in Human 3D Skin Model Injected with Resorbable Hyaluronic Acid Fillers Reveals Foreign Body

Danyel G J Jennen1, Marcel van Herwijnen1, Marlon Jetten1

  • 1Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University, 6200 Maastricht, The Netherlands.

International Journal of Molecular Sciences
|November 11, 2022
PubMed
Summary
This summary is machine-generated.

Injectable dermal fillers can cause adverse reactions like inflammation. This study used a 3D skin model to show hyaluronic acid fillers trigger inflammatory gene expression, with some causing mitochondrial dysfunction.

Keywords:
3D skin modeldermal fillershyaluronic acidinflammationtranscriptomics

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Area of Science:

  • Biomaterials Science
  • Dermatology
  • Molecular Biology

Background:

  • Injectable dermal fillers are increasingly used for aesthetic purposes.
  • Adverse reactions, including inflammation and migration, are a growing concern.
  • Understanding the molecular basis of these reactions is crucial for safety.

Purpose of the Study:

  • To investigate the molecular events underlying adverse reactions to dermal fillers.
  • To analyze gene expression changes in a 3D human skin model exposed to various fillers.
  • To assess the role of cross-linking degree and particle size in filler-induced responses.

Main Methods:

  • Genome-wide gene expression profiling of a Phenion® Full-Thickness Skin Model.
  • Exposure to experimental hyaluronic acid (HA) fillers, commercial HA fillers, and a non-resorbable filler.
  • Analysis of cytokine, chemokine, and mitochondrial gene expression patterns.

Main Results:

  • All tested HA fillers induced significant gene expression of inflammatory cytokines and chemokines.
  • One experimental filler led to down-regulation of OXPHOS genes, indicating mitochondrial dysfunction.
  • Mitochondrial dysfunction correlated with increased expression of pro-inflammatory mediators like TNFα and IL-1β.
  • Filler particle size showed a partial correlation with observed biological responses.

Conclusions:

  • Dermal fillers can mechanistically induce inflammatory and fibrotic responses.
  • Gene expression analysis in a 3D skin model provides insight into filler-related adverse reactions.
  • Findings support the link between filler properties, inflammation, and potential tissue responses.