Multitargeted approach for the optimization of morphogenesis and barrier formation in human skin equivalents

Arnout Mieremet, Richard W. J. Helder, Andreea Nadaban, Walter A. Boiten, Gert S. Gooris, Abdoelwaheb el Ghalbzouri, Joke A. Bouwstra

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

In vitro skin tissue engineering is challenging due to the manifold differences between the in vivo and in vitro conditions. Yet, three-dimensional (3D) human skin equivalents (HSEs) are able to mimic native human skin in many fundamental aspects. However, the epidermal lipid barrier formation, which is essential for the functionality of the skin barrier, remains compromised. Recently, HSEs with an improved lipid barrier formation were generated by (i) incorporating chitosan in the dermal collagen matrix, (ii) reducing the external oxygen level to 3%, and (iii) inhibiting the liver X receptor (LXR). In this study, we aimed to determine the synergic effects in full-thickness models (FTMs) with combinations of these factors as single-, double-, and triple-targeted optimization approaches. The collagen–chitosan FTM supplemented with the LXR inhibitor showed improved epidermal morphogenesis, an enhanced lipid composition, and a better lipid organization. Importantly, barrier functionality was improved in the corresponding approach. In conclusion, our leading optimization approach substantially improved the epidermal morphogenesis, barrier formation, and functionality in the FTM, which therefore better resembled native human skin.
Original languageEnglish
Article number5790
JournalInternational journal of molecular sciences
Volume22
Issue number11
DOIs
Publication statusPublished - 1 Jun 2021
Externally publishedYes

Keywords

  • Ceramides
  • Chitosan
  • Free fatty acids
  • Human skin equivalents
  • Hypoxia
  • Monounsaturated
  • Nuclear receptors/LXR
  • Skin

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