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

epidermal thickness of the wounded lesions in healthy subjects correlated with a decreased TEWL, suggesting epidermal and SC restoration after wounding.48

The use of the suction blister model has enabled studying skin barrier function in relations to epidermal wound healing, immune, and microvascular responses.48–50 However, it is a technique that can lead to the formation of uneven and different blister sizes, which have the potential to not heal properly and ultimately leave a scar.

Skin Irritants Model
Cutaneous irritation, as the natural skin response to an exogenous stimulus that elicits an inflammation reaction, is widely used as a clinical model to study acute barrier disruption. At the cellular level, anionic surfactants, such as sodium lauryl sulfate (SLS), are shown to cause damage to nucleated cells of the epidermis and to result in a dose-dependent inflammatory response.51,52 While organic solvents, such as acetone, disrupt the cohesion between the epidermal lipids lamellae at all levels of the SC.51

Under clinical conditions, the SLS-induced irritation model can be used to study skin sensitization in relations to skin barrier integrity under both physiological and pathological conditions. For instance, one study demonstrated that repeated SLS application over 3 weeks in non-atopic dermatitis (AD) subjects led to a decrease TEWL overtime and an increase in CER 1, suggesting a protective role for this CER species against chronic irritation.53 Another study showed that SLS skin sensitivity is only seen in patients with active AD, with an AD history or with atopic asthma, who have a tendency to have a higher basal TEWL level.54 These results are consistent with compromised SC barrier as the major contributing factor to skin irritation.

Skin irritants are effective methods to induce and study acute barrier impairment and lipids, plus inflammation in the clinics. The drawback of this model is depending on the skin condition, the irritants nature and concentrations used, length of exposure, and time at which each endpoint is assessed, will immensely vary the epidermal disruption and restoration processes.

Environmental Models
Solar radiation is one of the most prominent environmental skin stressors. The human skin is exposed to ultraviolet radiation (UVR), comprising of ~95% UVA (320–400 nm) and ~5% UVB (280–320 nm).55 Numerous models were developed to clinically evaluate the impact of UVR on skin barrier function.

For instance, single exposure to UVB and UVA was shown to increase the amount of SC triglycerides, FFAs, alkanes, and squalene in subjects with skin phototype II–III.56 Interestingly, UVB exposure alone can decrease intracellular lipid cohesion and change SC lipids and keratin structures.57 One research group evaluated the impact of acute UV exposure on skin biophysical properties on healthy Korean subjects with skin phototype II–IV. Although no information on skin barrier proteins and lipids were presented, they found that exposure to UV increased TEWL and decreased skin hydration in a dosedependent manner within 24 hours.58

In regard to repeated sun exposures, one research group evaluated the biological effects induced by semi-chronic exposure to simulated standard ultraviolet daylight (UV-DL) on subjects with skin phototype II–III; they showed that 9 doses of 0.25, 0.5, and 0.75 MED over 2 weeks with UV-DL caused significant decrease in skin hydration, but observed increased epidermal thickness only at 0.75 MED.59 Another popular method to study the impact of chronic UVR exposure is under real life conditions. For example, one group demonstrated that the chronic sun-exposed hands of middle-aged Japanese golfers were photodamaged and showed reduction in skin hydration, but interestingly no difference in TEWL compared to the glove-protected hands.60

UV exposure is shown to affect skin barrier integrity by increasing epidermal thickness, decreasing skin hydration, plus increasing skin lipids and proteins levels and modifying their structures. Due to different doses and sources of irradiations used in the literature, the impact of UV on TEWL and skin lipid in particular is inconclusive. Although not highlighted here, previous studies have also investigated the impact of age, seasons, and climate on skin barrier.61 It is important to note that the wavelength, length of exposure, intensity used, and subjects skin phototype and history are all important factors to take into consideration when studying the influence of environmental factors on skin barrier function.

Skincare Application
Intercellular SC lipids, CHOL, CERs and FFAs, are essential to maintain epidermal barrier homeostasis. Prior studies have shown that application of an equal ratio of SC lipids promotes normal repair and increasing the ratio of any of these lipid classes accelerated the recovery process.62 As discussed above, many models from in situ to clinical have since been used to study skin barrier function and to evaluate the efficacy of various natural and synthetic lipid mixtures for optimized barrier health.

As lipid abnormalities are often associated with impaired skin barrier integrity in several dermatologic conditions, SC intercellular lipids, particularly CERs, are now commonly used as main ingredients in moisturizers and other products for managing different skin disorders. For instance, it was observed that AD patients have decreased levels of CER 1 and 3, which was associated with an increased skin susceptibility