1. Multitargeted Approach for the Optimization of Morphogenesis and Barrier Formation in Human Skin Equivalents
- Author
-
Abdoelwaheb El Ghalbzouri, Richard W.J. Helder, Andreea Nadaban, Joke A. Bouwstra, Walter A. Boiten, Arnout Mieremet, Gert S. Gooris, and Medical Biochemistry
- Subjects
0301 basic medicine ,Keratinocytes ,Human skin ,Matrix (biology) ,Mass Spectrometry ,Chitosan ,030207 dermatology & venereal diseases ,chemistry.chemical_compound ,0302 clinical medicine ,X-Ray Diffraction ,Spectroscopy, Fourier Transform Infrared ,Morphogenesis ,Biology (General) ,monounsaturated ,nuclear receptors/LXR ,Spectroscopy ,Cells, Cultured ,Liver X Receptors ,integumentary system ,free fatty acids ,General Medicine ,Lipids ,Computer Science Applications ,Cell biology ,Chemistry ,Collagen ,skin ,QH301-705.5 ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Equivalent ,In vivo ,Scattering, Small Angle ,Humans ,Physical and Theoretical Chemistry ,Liver X receptor ,QD1-999 ,Molecular Biology ,ceramides ,Tissue Engineering ,hypoxia ,Organic Chemistry ,Lipid Metabolism ,In vitro ,030104 developmental biology ,chemistry ,Epidermal Cells ,human skin equivalents ,Epidermis ,Chromatography, Liquid - 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.
- Published
- 2021