TY - JOUR
T1 - Multitargeted approach for the optimization of morphogenesis and barrier formation in human skin equivalents
AU - Mieremet, Arnout
AU - Helder, Richard W. J.
AU - Nadaban, Andreea
AU - Boiten, Walter A.
AU - Gooris, Gert S.
AU - el Ghalbzouri, Abdoelwaheb
AU - Bouwstra, Joke A.
N1 - Funding Information: Funding: This research was funded by the Dutch Technology Foundation TTW (grant no. 13151), which was part of The Netherlands Organisation for Scientific Research (NWO), which was partly funded by the Ministry of Economic Affairs. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - Ceramides
KW - Chitosan
KW - Free fatty acids
KW - Human skin equivalents
KW - Hypoxia
KW - Monounsaturated
KW - Nuclear receptors/LXR
KW - Skin
UR - http://www.scopus.com/inward/record.url?scp=85106639840&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms22115790
DO - https://doi.org/10.3390/ijms22115790
M3 - Article
C2 - 34071405
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 11
M1 - 5790
ER -