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
Human skin equivalents (HSEs) are generated from isolated skin cells. As the primary function of the skin is to form a barrier, in this thesis the barrier properties of three HSEs were assessed and... Show moreHuman skin equivalents (HSEs) are generated from isolated skin cells. As the primary function of the skin is to form a barrier, in this thesis the barrier properties of three HSEs were assessed and compared with native human skin. The results show that all HSEs have a decreased skin barrier function compared to native human skin. Lipids in the outermost layer of the skin, the stratum corneum (SC), play a key role in this barrier function. The lipids in the HSEs are arranged in lipid lamellae, similarly as in human skin, but form a less crystalline organization. Investigation of the lipid composition reveals that all HSEs have an increased presence of mono-unsaturated fatty acids and reduced total fatty acid content compared to human SC, which most likely is responsible for the reduced density in lipid organization. Another group of lipids, the ceramides, show a comparable composition, although the HSEs have increa sed levels of acylceramides compared to native human SC. As we show that the culture conditions are of crucial importance for the SC lipid properties of HSEs, a future change is to optimize the culture conditions to improve epidermal lipid metabolism in HSEs, resulting in improved SC barrier properties Show less
