ARTICLE: Models to Study Skin Lipids in Relation to the Barrier Function: A Modern Update on Models and Methodologies Evaluating Skin Barrier Function

April 2021 | Volume 20 | Issue 4 | Supplement Individual Articles | s10 | Copyright © April 2021

Published online April 6, 2021

Rebecca Barresi, Hawasatu Dumbuya PhD, Xue Liu PhD, I-Chien Liao PhD

L’Oréal Research and Innovation, Clark, NJ

barrier compromised tissue conditions. Simulating different types of disease based on inflammatory reaction (psoriasis and atopic dermatitis), trauma (wound healing, photodamage), or abnormal cell behavior (melanoma, squamous cell carcinoma) have been explored to study site of action or drug efficacy. The cellular phenotype can be achieved by using patient donor cells, or adding cytokine cocktail to the tissue culture media.16 For the models mentioned, one of the critical readouts is the restoration of epidermal barrier function.

Barrier Function Measurements Used in Biofabricated Skin Models
The integrity of barrier function is critical when the tissue is used for assessment of dermal chemicals.18 There are multiple aspects to evaluate a biofabricated skin tissue barrier functionality. Table 1 lists the readouts used to determine the skin barrier function in biofabricated skin models.

Studying Skin Barrier Function in Human Inflammatory Diseased Models
Both psoriasis and atopic dermatitis (AD) are complex immune mediated skin disorders.24 Skin barrier dysfunction is a common feature among the patients. The barrier impairments include mutations in corneocytes, reduced lipids content and tight junction proteins, and increased transepidermal water loss.16

Psoriasis Models
Psoriasis is a chronic autoimmune condition whereby immune cells activate skin cells to secrete pro-inflammatory cytokines that intensifies the pro-inflammatory signaling cascade. From recent clinical studies, the secretion of INF-Y, IL-1, IL-6, IL-17, IL-22, and TNFα by polarized Th1 and Th17 cells are elevated in the plaque site.25 Adding these cytokines to the tissue culture media can generate typical phenotype of psoriasis skin including parakeratosis, reduced barrier differentiation protein (eg, filaggrin and loricrin), and increased level of hBD1 and SKALP.24,26 A psoriatic skin model generated by adding IL-22 to the media showed increased thickness of epidermis and used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technique to evaluate drug penetration with normal and diseased tissue.27 Fourier transform infrared spectroscopy (FTIR) and small angle x-ray diffraction (SAXD) have been frequently used in quantifying the SC lipid composition. MALDI-MSI is also a powerful technique which has the ability to detect the actives applied topically as well as the spatial location of lipids in the tissue.27,28 Some of the studies included all-trans retinoic acid (ATRA) in the treatment and demonstrated that this classic compound for treating psoriasis also has efficacy in rescuing filaggrin expression and improving the barrier function of the diseased model.24 This aligns with clinical studies, which proves that the diseased models can to be used for skin barrier research.

Engineered psoriatic skin model can also be developed by using patient donor cells.29 The self-assembly tissue showed disease phenotypes including reduction in keratinocyte differentiation, expression of CXCR2, and upregulated proinflammatory genes.30 Skin models that used psoriatic patient cells showed higher lipid disorder and change of protein conformation in the SC compared to the control tissue.31

Atopic Dermatitis Models
Similar to psoriasis, the tissue cultured with Th2 related cytokine IL-4 and IL-13 cytokines can also resemble AD.32 Several studies added IL-4 or IL-13 into the tissue culture media and the tissue carried impaired barrier features including intra-epidermal intercellular edema, abnormal expression of important differentiation proteins, and reduction in tight