Fetal wound healing: implications for minimal scar formation

The mid-gestation fetus is capable of regenerative healing with wound healing indistinguishable from surrounding skin. This review aims to evaluate the current knowledge of how the mid-gestation fetus heals without scar and the implications of these findings in efforts to recapitulate the fetal regenerative phenotype in the postnatal environment.

It has been over 30 years since the empirical observation that the fetus heals without scar; yet, the underlying mechanisms of this phenomenon have not been elucidated. Fetal wound healing is characterized by a distinct growth factor profile, an attenuated inflammatory response with an anti-inflammatory cytokine profile, an extracellular matrix rich in type III collagen and hyaluronan, attenuated biomechanical stress, and a potential role for stem cells. Current therapies to minimize scarring in postnatal wounds have attempted to recapitulate singular aspects of the fetal regenerative phenotype and have met with varying degrees of clinical success. We now have the molecular tools to more completely comprehend the fundamental mechanisms of fetal regenerative wound repair, which has the potential to provide insights into the identification of therapeutic targets to minimize the scar formation.

Successful therapies that help minimize postnatal scar formation can be realized through understanding the cellular and molecular mechanisms of fetal regenerative wound healing. These insights will have implications not only for cutaneous wound healing, but also potentially for any disease process characterized by excessive fibroplasia.