Improved skin substitutes and uses thereof

摘要

Improved Skin Substitutes and Uses Thereof Abstract The present invention relates to in vitro cultured skin substitutes, and in particular to in vitro cultured skin substitutes that have improved barrier function. In some 5 embodiments, improved barrier function is a result of improved culture conditions, while in other embodiments, improved barrier function results from genetic modification of keratinocyts. Improved culture conditions to improve barrier function include organotypic culture in the presence of linoleic acid and/or linoleic acid at about 75% humidity. Suitable genetic modifications for improving barrier function includes 10 transfection with a DNA construct capable of expressing GKLF. The present invention further provides improved methods of using such skin substitutes in the screening of compounds for irritancy activity, as well for identifying novel irritant responsive genes.