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Despite being widely used for basic and preclinical studies in dermatology, available animal models only partly recapitulate human skin features, often leading to disappointing outputs when preclinical results are translated to the clinic. Therefore, the need to develop alternative, non-animal models is widely recognized to more closely recapitulate human skin pathophysiology and to address the pressing ethical demand to reduce the number of animals used for research purposes, following the globally accepted 3Rs principle (Replacement, Reduction, and Refinement). Skin is the outermost organ of the body, and is, as such, easily accessible. Different skin cell types can be propagated in vitro, and skin can be reconstructed for therapeutic transplantation as well as for in vitro modelling of pathophysiological conditions. Bioengineered skin substitutes have been developed and have evolved from elementary to complex systems, more and more closely resembling complete skin architecture and biological responses. In silico analyses take advantage of the huge amount of data already available from human studies to identify and model molecular pathways involved in skin pathophysiology without further animal testing. The present review recapitulates the available non-animal models for dermatological research and sheds light on their prospective technological evolution.
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