Physical characterization of the stratum corneum of an in vitro human skin equivalent produced by tissue engineering and its comparison with normal human skin by ATR-FTIR spectroscopy and thermal analysis (DSC)
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Skin equivalent
Human skin
Barrier function
Corneocyte
Human skin is the largest organ of the body and is an effective physical barrier keeping it from environmental conditions. This barrier function of the skin is based on stratum corneum, located in the uppermost skin. Stratum corneum has corneocytes surrounded by multilamellar lipid membranes which are composed of cholesterol, free fatty acids and ceramides (CERs). Alterations in ceramide content of the stratum corneum are associated with numerous skin disorders. In recent years, CERs have been incorporated into conventional and novel carrier systems with the purpose of exogenously applying CERs to help the barrier function of the skin. This review provides an overview of the structure, function and importance of CERs to restore the barrier function of the skin following their topical application.
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The stratum corneum (SC) is the uppermost tissue of the skin. It protects the body against external impacts and prevents it from desiccation. The stratum corneum is a thin tissue of ∼20 µm, which is mainly composed of two fractions: lipids and proteins. The proteins are located in the corneocytes and these cells are embedded in a continuous lipid matrix.
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Corneocyte
Transepidermal water loss
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Lamellar granule
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Skin equivalent
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Skin tissue may be engineered in a variety of ways. Our cultured skin substitute (Graftskin, living skin equivalent or G-LSE), Apligraf™, is an organotypic culture of skin, containing both a "dermis" and "epidermis." The epidermis is an important functional component of skin, responsible for biologic wound closure. The epidermis possesses a stratum corneum which develops with time in culture. The stratum corneum provides barrier function properties and gives the LSE improved strength and handling characteristics. Clinical experience indicated that the stratum corneum might play an important role in improving the clinical utility of the LSE. Handling and physical characteristics improved with time in culture. We examined the LSE at different stages of epidermal maturation for barrier function and ability to persist as a graft. LSE grafted onto athymic mice before significant development of barrier function did not withstand bandage removal at 7 days postgraft. LSE grafted after barrier function had been established in vitro were able to withstand bandage removal at day 7. Corneum lipid composition and structure are critical components for barrier function. Media modifications were used in an attempt to improve the fatty acid composition of the stratum corneum. The barrier developed more rapidly and was improved in a serum-free, lipid-supplemented condition. Lipid lamellar structure was improved with 10% of the stratum corneum exhibiting broad-narrow-broad lipid lamellar arrangements similar to human skin. Fatty acid metabolism was not appreciably altered. Barrier function in vitro was 4- to 10-fold more permeable than human skin. Epidermal differentiation does not compromise engraftment or the wound healing ability of the epidermis. The stratum corneum provides features beneficial for engraftment and clinical use. © 1996 John Wiley & Sons, Inc.
Barrier function
Corneocyte
Epidermis (zoology)
Lamellar granule
Skin equivalent
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Human skin
Epidermis (zoology)
Corneocyte
Raman microspectroscopy
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To advance drug development representative reliable skin models are indispensable. Animal skin as test model for human skin delivery is restricted as their properties greatly differ from human skin. In vitro 3D-human skin equivalents (HSEs) are valuable tools as they recapitulate important aspects of the human skin. However, HSEs still lack the full barrier functionality as observed in native human skin, resulting in suboptimal screening outcome. In this review we provide an overview of established in-house and commercially available HSEs and discuss in more detail to what extent their skin barrier biology is mimicked in vitro focusing on the lipid properties and cornified envelope. Further, we will illustrate how underlying factors, such as culture medium improvements and environmental factors affect the barrier lipids. Lastly, potential improvements in skin barrier function will be proposed aiming at a new generation of HSEs that may replace animal skin delivery studies fully.
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Transepidermal water loss
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A variety of abnormalities of the uninvolved skin have been reported in psoriasis, but there are few studies in which abnormalities of the stratum corneum (SC) have been investigated. In this study we have examined the intracorneal cohesion and structural detail of corneocytes of the SC from involved and uninvolved sites in 24 patients with psoriasis and 10 controls. We have found that intracorneal cohesion is increased in the involved and uninvolved skin of psoriatic patients compared to controls and that there are abnormalities of stratum corneum and corneocyte structure as determined by scanning electron microscopy. The changes in the uninvolved sites may well be due to the increased rate of epidermal cell production in these areas.
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