Composite of microgels and lipids as biofilm to restore skin barrier function

Abstract

The mature epidermis is an effective barrier which prevents the body from dehydration and protects it against various environmental influences. If the natural barrier is immature or damaged, the skin barrier is impaired and desiccation occurs. Hence, the regeneration of impaired skin is an essential process for survival. In patients, the natural recovery is sometimes rather slow, in particular in the cases of large defects. To support skin regeneration, a large variety of skin creams is presently available, aiming to modify the hydration level of the skin and to protect the body against excessive water loss and thus to enhance epidermal barrier function. However, these creams clearly have a different structure than stratum corneum (SC), resulting in low water binding capacity and uncontrolled hydration of the skin. The basic mechanism of these skin creams is that they act as moisturizer and increase the hydration of SC by either blocking the TEWL (transepidermal water loss) or by delivering exogenous hygroscopic substances to the SC. Therefore, it has been suggested that the development of barrier creams with high water-holding capacity and thus controlled water transport, such as the natural cream VC (vernix caseosa), might help in the development and/or restoration of the SC barrier. The aim of this thesis was the development of a new generation of skin-surface biofilms, combining the structure and properties of VC, to protect diseased, dry and premature skin and to facilitate wound healing. These biofilms were based on synthetic cells embedded in a lipid matrix. The synthetic cells consisted of crosslinked hydrophilic polymers (hydrogels) with similar size and shape as natural corneocytes. Combined with the work of Rissmann (presented in thesis R. Rissmann), who focused on the development of a synthetic lipid mixture, we were able to prepare biofilms. The biofilms were prepared by mixing the synthetic corneocytes with the lipid matrix. These biofilms were characterized and optimized to mimic VC. Various biofilms were applied topically on disrupted mouse skin to investigate their effect on superficial wound healing. All formulations promoted a rapid formation of SC and prevented epidermal hyperproliferation. In general the synthetic VC analogues showed strong effects concerning the recovery rate, however, only one biofilm mimicked the effects of native VC the most closely. In conclusion, this thesis describes the development of a new generation of skin-surface biofilms mimicking closely the structure and properties of VC. These biofilms act as skin protectants and facilitate the restoration of the SC barrier. These unique systems have therefore great potential to protect diseased, dry and premature skin and to facilitate wound healing in humans.