Skin is one of the major ways of communication between organism and environment and, as such, a possible route of administration for topical or transdermal drugs. Thanks to its organization in different layers, skin constitutes an excellent physical, immunological and sensory barrier, playing an important protective role against microbial attack, UV irradiation and chemicals of different types. It follows a crossing difficulty even for active compounds designed for therapeutic purpose. The currently available in vitro systems that try to mimic the cutaneous barrier are cell cultures, from conventional mono-layer cell cultures to more advanced three-dimensional co-cultures. They are widely accepted but certainly simplistic models compared to the real physiological structure and dynamic behavior of a living organism [1, 2]. The information gathered by tests on these in vitro models is therefore insufficient and in vivo experimentation still remains largely used, despite the 3Rs principles encourages a reduction and rationalization in the use of laboratory animals. The key challenge is therefore the development of an in vitro model able to be more predictive mimicking better the skin barrier, in order to fill the huge gap between in vitro and in vivo research. In this perspective, an innovative in vitro system for explanted skin testing has been developed by modifying a bioreactor for cell culture and has been evaluated for its ability to preserve skin samples in a fluid dynamic environment closer to the in vivo conditions.