The protective function of the epidermal barrier assumes a vital multifaceted role in safeguarding the body from environmental perturbations and in regulating transcutaneous permeation. The Stratum Corneum (SC) confers indispensable and dynamic attributes impartinga hydrophobic shield. This barrier maintains a delicate equilibrium essential for the preservation of skin health, thereby mitigating manifestations of sensitivity. Structurally, the SC exhibits a stratified arrangement and can be conceptualized as a composite material structured according to « brick and mortar » architecture, wherein a proteinaceous framework (corneocytes) is ensconced within a lipidic scaffold (intercellular lipids).

The «mortar» in this analogy denotes lipids, or lamellar membranes, enveloping corneocytes. Epidermal cells synthesize these, storing them in keratinocytes as lamellar bodies. As keratinocytes ascend into the stratum corneum, these bodies are discharged into the extracellular matrix surrounding corneocytes, forming lamellar membranes. A balanced 1:1:1 ratio of sterols, ceramides, and free fatty acids within lamellar membranes maintains a healthy permeability barrier, crucial for preventing water loss and the ingress of allergens, free radicals, toxins, and microorganisms.

Despite comprising «dead» corneocytes, the stratum corneum exhibits metabolic activity, employing enzymes and cytokines for desquamation, inflammation reduction, lipid synthesis, and cell proliferation. The stratum corneum’s surface forms the acid mantle, whose pH, when disturbed, initiates natural healing mechanisms. Yet, chronic acid mantle damage induces sustained inflammation and diminishes UVB protection and moisture retention capacities.

Skin barrier integrity can be evaluated using skin explants or 3D reconstructed skin models, measuring Transepithelial/transendothelial electrical resistance (TEER) or the permeation of molecules through the epidermis via Franz Cell or other methods. The formation and renewal of this integrity are linked to keratinocyte proliferation, differentiation, and desquamation. Biomarkers like keratins, transglutaminases, and filaggrin control these processes. Components of the dermal-epidermal junction, including Laminin 332 and integrins, affect keratinocyte survival and barrier function. Tight junction proteins like Corneodesmosin and Zonula Occludens 1 maintain cohesion between corneocytes, crucial for preventing molecule transfer. Lipid composition, thickness, and organization are vital for barrier function and can be assessed using Raman microspectroscopy and liquid chromatography coupled with mass spectrometry, offering insights into ceramide synthesis and organization. Proper hydration and pH are essential for enzyme function in stratum corneum formation. Overall, these methods provide comprehensive evaluation of skin barrier function at various levels.

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