Human Skin Model to Target Sensitive Skin and Soothing Effects by Syntivia

12 June 2023

At pathophysiological level, sensitive skin is characterized by several phenomena: a defect in the cutaneous barrier, as well as increased inflammation and neuroinflammation. These phenomena lead to skin dryness, irritation and sometimes burning sensations.

At Syntivia, they are committed to providing studies that are as close as possible to in-vivo conditions and have chosen the skin explant as their favoured model. As the explant is obtained from surgically derived human skin, it is for them, the most representative of the complexity of human skin.

Despite its complexity, they can adapt the ex vivo model to many cosmetic and dermatological applications to evaluate the biological effects of products under development or finish products.

They are working on a human skin model with a barrier defect, dehydration and expressing the main markers of sensitive skin (figure 1).

Figure 1: Preparation of a preclinical ex vivo model of irritated skin and imaging after histological staining

Barrier defect and skin dehydration:

In addition to the thinning of the stratum corneum resulting from tape stripping (figure 1), the model shows a decrease in the main markers of the stratum corneum (figure 2):

Filaggrin
Ceramides
Loricrin (not shown)
Involucrin (not shown)

They also observe a significant increase in TEWL and a decrease in the amount of glycerol present in the skin (figure 2). Indeed, a low concentration of glycerol may lead to decrease the water content of both epidermal and dermal compartments, possibly leading to structural changes in the skin relief and increasing the TEWL.

Figure 2 : Barrier alteration and skin dehydration in the preclinical ex vivo model of irritated skin.

Activation of inflammatory mediators:

The model they use is also characterized by the production of cytokines associated with non-specific inflammation: Tumor Necrosis Factor a (TNFa) and Prostaglandin E2 (PGE2), the latter being particularly associated with sensitive skin (figure 3).

Transient Receptor Potential, Vanilloid Family 1 (TRPV1) is a thermosensitive ion channel which reacts to noxious stimuli. TRPV1 is expressed among other on fibroblasts, mast cells and keratinocytes; activation results in pain or pruritus with a burning component. TRPV1 expression is increased in the skin model and probably upregulated by inflammatory mediators (Figure 3).

Figure 3 : Increase of markers associated to inflammation and neuroinflammation in the preclinical ex vivo model of irritated skin

In conclusion, this ex vivo model, as a real human skin model of irritated skin, responds very closely to the vivo conditions, and perfectly bridges the gap between in vitro activity and clinical studies, increasing the chances of success in clinical studies.

The multiplicity of markers they can study means they can effectively screen products for their activity, highlighting both products that help reduce the signs of sensitive skin, and those that are potentially irritating.

They are continuing their research to identify new conditions that can cause skin irritation through different external stresses (molecules, viruses, detergents…) to offer ever more evaluation possibilities for ever more reliable results.

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