Mieremet Arnout, Rietveld Marion, Absalah Samira, van Smeden Jeroen, Bouwstra Joke A, El Ghalbzouri Abdoelwaheb
Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands.
Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.
PLoS One. 2017 Mar 23;12(3):e0174478. doi: 10.1371/journal.pone.0174478. eCollection 2017.
Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan. Herein, we report that these collagen-chitosan FTMs (CC-FTMs) possess a well-organized epidermis and maintain both the early and late differentiation programs as in FTMs. Distinctively, the epidermal cell activation is reduced in CC-FTMs to levels observed in NHS. Dermal-epidermal interactions are functional in both FTM types, based on the formation of the basement membrane. Evaluation of the barrier structure by the organization of the extracellular lipid matrix of the stratum corneum revealed an elongated repeat distance of the long periodicity phase. The ceramide composition exhibited a higher resemblance of the NHS, based on the carbon chain-length distribution and subclass profile. The inside-out barrier functionality indicated by the transepidermal water loss is significantly improved in the CC-FTMs. The expression of epidermal barrier lipid processing enzymes is marginally affected, although more restricted to a single granular layer. The novel CC-FTM resembles the NHS more closely, which makes them a promising tool for epidermal barrier related studies.
全层人类皮肤模型（FTMs）包含表皮和真皮等效物。后者由含有成纤维细胞的胶原真皮基质组成。FTMs目前的表皮屏障特性并不完全类似于天然人类皮肤（NHS），这使得这些人类皮肤模型不太适合用于屏障相关研究。为了进一步增强NHS在表皮形态发生和屏障形成方面的相似性，我们用生物相容性聚合物壳聚糖对胶原真皮基质进行了调节。在此，我们报告这些胶原-壳聚糖FTMs（CC-FTMs）拥有组织良好的表皮，并像在FTMs中一样维持早期和晚期分化程序。独特的是，CC-FTMs中的表皮细胞活化降低到了在NHS中观察到的水平。基于基底膜的形成，两种FTM类型中的真皮-表皮相互作用都是功能性的。通过角质层细胞外脂质基质的组织对屏障结构进行评估，发现长周期相的重复距离延长。基于碳链长度分布和亚类概况，神经酰胺组成与NHS表现出更高的相似性。经表皮水分流失所表明的由内而外的屏障功能在CC-FTMs中得到显著改善。表皮屏障脂质加工酶的表达受到轻微影响，尽管更多地局限于单个颗粒层。新型CC-FTM与NHS更相似，这使其成为表皮屏障相关研究的一个有前途的工具。
