3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function.

Hanna Niehues,Abdoelwaheb El Ghalbzouri,Johanna M Brandner,Ellen H Van Den Bogaard,Joke A Bouwstra,Patrick L J M Zeeuwen

doi:10.1111/exd.13531

Abstract

The skin barrier is an important shield regulating the outside-in as well as inside-out penetration of water, nutrients, ions and environmental stimuli. We can distinguish four different barrier compartments: the physical, chemical, immunological and microbial skin barrier. Well-functioning of those is needed to protect our body from the environment. To better understand the function and the contribution of barrier dysfunction in skin diseases, 3D skin or epidermal models are a valuable tool for in vitro studies. In this review, we summarize the development and application of different skin models in skin barrier research. During the last years, enormous effort was made on optimizing these models to better mimic the in vivo composition of the skin, by fine-tuning cell culture media, culture conditions and including additional cells and tissue components. Thereby, in vitro barrier formation and function has been improved significantly. Moreover, in this review we point towards changes and chances for in vitro 3D skin models to be used for skin barrier research in the nearby future.

Highlights

The 3D skin models available to date will certainly advance over the coming years by the optimization of culture conditions, but already in vitro cultured 3D skin models have been proven to be an excellent alternative for, or addition to, experimental animal models to study skin biology, wound healing, skin ageing and disease pathology.[96,159,160,161,162,163]
One could speculate that the sterile environment of cultured 3D skin models lacks important stimuli for a normal skin barrier function to be established
The host-microbe interaction between keratinocytes and microbiota could be a key factor for achieving the skin barrier function we observe in native skin

Summary

Introduction

Many features of a fully stratified epidermis are lacking in this model and keratinocytes are forced to adapt to artificial circumstances, like a flat surface and submerged culture, which may alter gene expression and cell function.[31] To study cell-cell interactions, regulation of proliferation and differentiation, wound healing, skin barrier function and skin-microbiome interactions, 3D skin models better resemble the natural architecture and functions of the skin and should be considered as the gold standard when performing in vitro studies on human skin.

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