Exogenous Factors in Skin Barrier Repair

In this article, the basic components of the SC and how it’s structure and function serve to regulate moisture homeostasis of the skin will be reviewed. The various exogenous and endogenous factors that can disrupt the skin barrier and, therefore, affect the moisture content of the skin will be discussed. The overarching focus will be on the successful maintenance, regulation, and repair of the SC based on using over-the-counter moisturizers, with a strong emphasis on the impact of active ingredients and delivery vehicles on skin barrier health.

Although often depicted as the inert portion of the epidermis, the SC is actually a highly dynamic layer of cells that is essential to maintaining skin moisture homeostasis.¹ In order to understand how the SC functions in skin hydration and how topically applied moisturizers serve to enhance hydration and restore the barrier, it is important to understand the primary components of the SC and how they are formed.The primary cell of the epidermis is the keratinocyte, which is derived from stem cells in the bottom-most basal layer of the epidermis. As the keratinocytes migrate up through the spinous and granular layers they differentiate, lose their nuclei, and eventually form the SC, or cornified layer. The process of keratinocyte migration from the basal layer until it is shed from the surface of the SC is approximately 28 days.²The structure of the SC is most often visualized as a “brick and mortar” configuration.³ The “bricks” are the flat and hexagonal, anucleate keratinocytes, now known as corneocytes, stacked in layers. Instead of a typical plasma membrane, the corneocytes are surrounded by the cornified envelope, which is made up of cross-linked proteins derived from keratohyalin granules.⁴ Corneodesmosomes, the SC equivalent of desmosomes in the epidermis, connect the corneocytes and contribute to the structural integrity of the SC.⁵ The “mortar” of the SC consists of natural moisturizing factors (NMF) and lipids. NMF is a rich combination of products produced from the breakdown of filaggrin on the surface of the keratinocyte and includes amino acids and their derivatives, lactic acids, urea, and salts.⁶ NMF’s primary function is to attract and bind water in order to maintain moisture homeostasis in the SC.⁶ The intercellular lipids are made from lamellar granules, which are formed from the degradation of keratinocytes transitioning from the granular layer into the cornified layer, and the breakdown products of corneocyte membranes.⁷ Lamellar lipids are primarily composed of free cholesterol, free fatty acids, and sphingolipids.⁴ Ceramide is a unique sphingolipid that has both a hydrophobic and hydrophilic component, allowing simultaneous binding of water and impermeability to the SC, which prevents loss of moisture to the environment.⁸The SC works primarily in two ways to maintain moisture in the skin: through the maintenance of NMF and desquamation. The water content of healthy skin ranges from 15-25% at the skin surface and approximately 40% at the transition point between the granular layer and the SC.⁹ Water is crucial to the skin because it helps maintain plasticity and texture. The loss of water from the epidermis is coined transepidermal water loss (TEWL). As mentioned above, NMF is one of the vital components of the mortar of the SC. The product of NMF from filaggrin breakdown is directly proportional to corneocyte water content so that in dry conditions, proteolytic enzymes are stimulated to degrade