In vivo, epithelial tissues are continuously in contact with the external environment. To mimic such condition in vitro the air-liquid interface (ALI) approach is widely adopted, which is traditionally obtained by using a transwell inserted in a well for separating the liquid and air compartments. However, such static environment lack in mimicking the in vivo nutrient and gas transport provided by the native microvasculature, leading to gradient formation within the culture. To overcome this limitation, culture medium recirculation can be adopted, knowing that it is crucial to avoid air bubbles stagnation under the ALI, to prevent sample drying. Indeed, the aim of this thesis was the optimization and validation of a biomimetic bioreactor for ALI culture with recirculating culture medium (RCM), to be used for skin tissue engineering investigations.