In vivo, epithelial tissues are directly exposed to the external environment. To replicate this condition in vitro, the air–liquid interface (ALI) approach is widely used. Traditionally, ALI is obtained using a transwell insert with a semipermeable membrane placed in a well to separate the liquid and the air compartments. However, this static culture environment does not mimic the nutrient and gas transport provided by the native microvasculature, leading to nutrient gradients. To overcome this limitation, culture medium recirculation can be adopted. In this context, this thesis aims to optimize, prototype, characterize and validate an ALI culture environment (ALIce) bioreactor with a recirculating medium system for skin tissue engineering applications.