Hydrogen peroxide disrupts scarless fetal wound repair

Abstract

Cutaneous wound healing is a complex process that leads to the formation of a permanent scar in adult skin. In contrast, early gestation fetal skin undergoes scarless repair. Normally, the repair process in the skin begins with an acute inflammatory response. However, one of the most important aspects of scarless fetal wound repair appears to be a lack of inflammation, suggesting that inflammation promotes scar formation in the skin. While it is well accepted that inflammation causes scar formation in the fetus, it is not known what specific factors produced during inflammation are responsible for these effects. Oxidants released by activated inflammatory cells have the potential to be involved, although this has never been examined. The present studies, using a murine fetal wound repair model, show that hydrogen peroxide interferes with scarless healing, possibly through the induction of transforming growth factor-beta1. Hydrogen peroxide also increased the proliferation of fetal fibroblasts, which could contribute to an increase in the fibrosis seen with hydrogen peroxide. Defining the factors produced during the inflammatory response that contribute to scar formation could be important for the development of new therapies designed to minimize scarring.