Developing an in vitro 3D model replicating psychologically stressed skin

Summary: Abstract Body: Psychological stress (PS) affects both physical and emotional homeostasis. Stress can exert multiple and deleterious wide-ranging physiologic and clinical impacts on peripheral tissues, including skin. Moreover, stress exacerbates existing skin conditions such as acne and atopic dermatitis and can accelerate the appearance of aging. One mechanism by which stress affects the skin is by weakening the skin barrier through inhibition of keratinocyte proliferation and differentiation and decreased secretion of lamellar bodies and density of corneodesmosomes. PS triggers the activation of the hypothalamic-pituitary-adrenal (HPA) axis which induces the release of stress-related neurotransmitters and hormones (e.g., the glucocorticoids cortisol/cortisone). Skin barrier dysfunction is, in part, a result of the excessive release of glucocorticoids. While much research has been conducted on individual neurotransmitters and hormones in mouse models or 2D culture systems of skin cell subtypes, less is known about changes in 3D skin-equivalent tissues or molecular changes of keratinocytes in chronically stressed human skin. Understanding the effects of PS on the skin is crucial for developing effective strategies to mitigate its impact. In this study we aim to 1) develop an in vitro 3D skin model to assess the effects of PS and 2) test whether topically applied actives can reduce the effects of stress on the PS skin model. The PS skin model was developed by topically applying actives targeting the cortisol pathway in formulation, followed by addition of cortisol or cortisone, the inactive form of cortisol, to the media of 3D skin-equivalent tissues (MatTek EpiDerm-FT). Consequently, we created a model to replicate some of the effects of PS through applying key stress hormones (cortisol/cortisone) to a skin equivalent 3D tissue model and identified actives that can reduce excessive cortisol release. These ingredients provide options for future skincare product development aimed at reducing the effects of PS on skin. Morgan Dragan¹, Ericka Yap¹, Chris Tian¹, Patrick Nido¹, Prithwiraj Maitra¹, Kuniko Kadoya¹ 1. Skincare, AbbVie Inc, North Chicago, IL, United States. Translational Studies: Cell and Molecular Biology