Workman V L, Giblin A-V, Green N H, MacNeil S, Hearnden V
Department of Materials Science and Engineering, University of Sheffield, Sheffield, UK.
Department of Plastic Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
In Vitro Model. 2023 Sep 21;2(6):297-306. doi: 10.1007/s44164-023-00058-9. eCollection 2023 Dec.
Tissue-engineered models of skin have evolved over the past 50 years, have successfully been translated to clinical use and continue to be improved using new technologies. However, very few of these constructs incorporate a hypodermal component. The hypodermis is critical to skin homeostasis, skin function and many skin diseases, but our understanding of the hypodermis is limited in comparison to our knowledge of the epidermis and dermis, in part due to a lack of suitable in vitro models. The purpose of this study was to develop and characterise a tissue-engineered model of skin consisting of epidermal, dermal and hypodermal layers, namely a trilayer skin model. Models were produced by culturing human keratinocytes and fibroblasts on decellularised human dermis in combination with explanted human adipose tissue. Bilayer models of skin, comprising of an epidermis and dermis, had a thicker epidermal component compared to trilayer models but exhibited similar cytokeratin expression patterns (AE1/AE3 and cytokeratin 14). Addition of adipose tissue improved the appearance of the dermal-epidermal junction, increased the number of rete ridge-like features and cells maintained similar levels of proliferation (Ki-67) compared to native tissues over 28 days in culture. This technique enabled us to create a physiologically relevant model of human skin with representative morphology across the hypodermis, dermis and epidermis. This model maintained native extracellular matrix architecture, contained a heterogeneous population of cells and has the potential to be applied to a range of different applications where research questions require the inclusion of a hypodermis.
The online version contains supplementary material available at 10.1007/s44164-023-00058-9.
在过去50年里，组织工程化皮肤模型不断发展，已成功转化为临床应用，并持续借助新技术加以改进。然而，这些构建体中很少有包含皮下成分的。皮下组织对皮肤稳态、皮肤功能及许多皮肤疾病至关重要，但与我们对表皮和真皮的了解相比，我们对皮下组织的认识有限，部分原因是缺乏合适的体外模型。本研究的目的是开发并表征一种由表皮、真皮和皮下层组成的组织工程化皮肤模型，即三层皮肤模型。通过将人角质形成细胞和成纤维细胞接种在脱细胞人真皮上，并结合植入的人脂肪组织来制作模型。由表皮和真皮组成的双层皮肤模型与三层模型相比，表皮成分更厚，但细胞角蛋白表达模式相似（AE1/AE3和细胞角蛋白14）。添加脂肪组织改善了真皮 - 表皮交界处的外观，增加了 rete 嵴样特征的数量，并且在培养28天期间，与天然组织相比，细胞维持了相似的增殖水平（Ki-67）。这项技术使我们能够创建一个具有生理学相关性的人皮肤模型，其在皮下组织、真皮和表皮具有代表性形态。该模型保留了天然细胞外基质结构，包含异质性细胞群体，并且有潜力应用于一系列不同的应用中，这些应用中的研究问题需要包含皮下组织。
在线版本包含可在10.1007/s44164-023-00058-9获取的补充材料。
