4.2.1. Skin Establishing normal physiology and function in a traditional 2D in vitro cell culture of skin is almost impossible. The advent of organotypic culture systems does allow approximation of skin complexity. 3D culture of skin allows dermatological studies which would otherwise be unsafe for animals and humans such as validating the mechanisms of skin diseases and testing the therapeutic potential of experimental drugs [135]. Developing a 3D in vitro human skin co-culture model has shown promise for detecting skin irritants as an alternative to in vivo animal testing [136].