Engineering a Pigmented Skin Equivalent That Is Responsive to External Stimuli.

Recently, dermatological research has more widely adopted the use of human skin equivalents (HSEs) to better recreate skin structure and function in vitro, which can act as a preclinical tool. However, many popular HSEs contain only two main cell types: keratinocytes and fibroblasts to model epidermal and dermal compartments respectively. This lack of supporting cell types can be associated with a wide range of limitations, most notably an inaccurate representation of skin's innate response to exogenous stressors such as UV radiation. We have adapted our novel full-thickness skin platform to incorporate human melanocytes that produce melanin and transfer melanin to neighboring keratinocytes, where it is located apically to the nucleus, forming typical supranuclear protective caps. The use of Alvetex scaffold and the ability of dermal fibroblasts to secrete their own endogenous extracellular matrix (ECM) proteins provide a robust dermal foundation for the construction of a pigmented epidermis and are essential for supranuclear cap formation, a physiological phenomenon essential to melanin's protective function. This model system is responsive both to up and downregulation of melanogenesis, therefore providing an in vitro platform for a wide array of applications, ranging from industrial active testing for cosmetic formulations to academic insights into the cellular response to environmental stressors.