Abstract: Methods and testing models for use in testing the effects of substances on human skin without the need for human subjects. The present invention includes a flap having viable, functional human skin on one side and animal skin on the opposite side. Sandwiched between the layers of skin are one or more isolated veins, arteries, and nerves. This isolated vasculature joins the animal and the skin flap. The human skin layer is simply a split thickness skin graft prepared from living, but discarded, human skin. The present invention allows various substances to be applied directly to the human skin. The presence of absence of the substance can then be detected in the blood flowing in the isolated vasculature. Thus, tests involving living human skin can be performed without the need to directly involve human subjects.