Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Division of BioTherapeutics, Leiden Academic Centre of Drug Research, Leiden University, 2333 CD Leiden, The Netherlands.
Int J Mol Sci. 2021 May 28;22(11):5790. doi: 10.3390/ijms22115790.
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.
体外皮肤组织工程具有挑战性，因为体内和体外条件存在多方面的差异。然而，三维（3D）人体皮肤等效物（HSE）在许多基本方面能够模拟天然人体皮肤。然而，表皮脂质屏障的形成对于皮肤屏障的功能仍然是有缺陷的。最近，通过以下方式生成了具有改善的脂质屏障形成的 HSE：（i）将壳聚糖纳入真皮胶原基质中，（ii）将外部氧水平降低至 3%，以及（iii）抑制肝 X 受体（LXR）。在这项研究中，我们旨在确定这些因素的组合在全厚度模型（FTM）中的协同效应，这些组合采用单、双和三目标优化方法。用 LXR 抑制剂补充壳聚糖的胶原 FTM 显示出改善的表皮形态发生、增强的脂质组成和更好的脂质组织。重要的是，相应方法改善了屏障功能。总之，我们的主导优化方法极大地改善了 FTM 中的表皮形态发生、屏障形成和功能，因此更类似于天然人体皮肤。
