The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix. The lipid matrix, consisting of ceramides, fatty acids, and cholesterol, is crucial for a... Show moreThe stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix. The lipid matrix, consisting of ceramides, fatty acids, and cholesterol, is crucial for a proper skin barrier function. In inflammatory skin diseases the lipid composition and ordering is altered contributing to the impaired skin barrier. Vernix caseosa (VC) is the cheesy, white cream that covers the skin of the human fetus. Application of an in house developed synthetic VC enhanced skin barrier repair in mice. Currently, there are no suitable skin models available to study human skin barrier repair after application of a topical formulation. This thesis describes the development of a human skin barrier repair model and evaluates VC based formulations using this model. The results demonstrate that the barrier of this repair model mimics several aspects of inflammatory skin diseases. Additionally, it was shown that the lipid properties in this model were improved when a synthetic VC-based formulation was applied. Based on the outcome, clinical studies were performed. These studies showed that application on a disrupted human skin barrier in vivo enhanced the barrier repair. However, the effects of the formulation are limited when applied on atopic dermatitis skin Show less
The skin barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which consists of dead corneocytes embedded in a highly organized extracellular lipid matrix.... Show moreThe skin barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which consists of dead corneocytes embedded in a highly organized extracellular lipid matrix. The lipids are thought to play a crucial role in the skin barrier function. This lipid matrix consists mainly of ceramides, cholesterol and free fatty acids in an approximately equimolar ratio. Atopic eczema (AE) is a chronic relapsing inflammatory skin disease that is characterized by dryness, erythema and pruritus. AE patients have a decreased skin barrier function as monitored with transepidermal water loss. The main objective of this thesis is to determine the SC lipid composition, lipid organization and lipid/protein ratio in AE patients and control subjects and to determine how these changes are associated with the impaired skin barrier function and disease severity of AE patients. The studies demonstrate that there is an altered lipid composition and lipid/protein ratio in non-lesional as well as lesional SC of AE patients. The changes in lipid composition result in an altered lipid organization that is associated with an impaired skin barrier function in AE patients Show less
Vernix caseosa (VC) is the cheesy, white cream that covers the skin of the human fetus and the newborn. VC is a protective cream, which consists of water containing dead cells that are embedded in... Show moreVernix caseosa (VC) is the cheesy, white cream that covers the skin of the human fetus and the newborn. VC is a protective cream, which consists of water containing dead cells that are embedded in lipids. This natural cream is suggested to feature multiple biological functions such as facilitating the skin formation during pregnancy and hydrating the skin of the newborn. The aim of this thesis was the rational design of synthetic creams which mimic VC__s structure and its unique properties. Synthetic creams were made of highly hydrated synthetic particles embedded in wool wax and skin lipids. These creams were shown to mimic excellently the structure and composition of natural VC, while the water content and release properties could be controlled. The developed creams showed their great potential for disrupted and underdeveloped skin concerning several aspects: the skin barrier recovery rate was drastically reduced, crust formation was prevented and thickening of the epidermis was less frequently observed. These promising results give rise to future clinical studies in order to prove the benefits of the newly developed creams to treat healthy, dry and diseased human skin. Show less
