To present the first human clinical data on an investigational living skin graft replacement that is being designed for application where tissue has been lost through surgery, disease or trauma. The ICX-SKN skin graft replacement is composed of an autosynthesized human collagen-based extracellular matrix and human dermal fibroblasts. In a first study to examine integration and persistence, full-thickness excisional wounds were made in six healthy human female volunteers and the ICX-SKN skin graft replacement applied and dressed. The surgical wounds were examined for up to 28 days post-application and the graft excised from each volunteer. Pre-excision gross examination revealed that the ICX-SKN skin graft replacement had integrated well in each of the six wounds and that re-epithelialization had occurred in each case. Histological analysis revealed that the ICX-SKN skin graft replacement remained in place and had become vascularized and provided a continuous wound closure. No serious adverse events were reported and no gross scarring or wound contracture was evident in the healed wounds. This is the first report of preliminary evidence indicating the persistence of an autosynthesized, tissue-engineered, living human skin substitute in healed acute wounds in humans.