Re‐epithelialization of wounds

Shortly after wounding, epithelial keratinocytes become activated through the combined effects of the exposure to pro‐migratory matrix molecules within the wound site and to growth factors that are released by other wound cells and from the blood clot as well as by wound‐generated electrical fields. Within 24 hours, they start migrating from the wound edges into the fibrin–fibronectin‐rich blood clot. They also deposit their own matrix molecules that facilitate their motility, including EDA fibronectin, laminin‐332, and tenascin‐ C as well as express their receptors (mainly integrins). Basal keratinocytes adjacent to the wound site start proliferating 48–72 hours after the injury, contributing to the migrating cell pool. Re‐epithelialization is stimulated by a number of cytokines and growth factors such as members of the epidermal growth factor, transforming growth factor‐β, and keratinocyte growth factor families that promote keratinocyte migration and proliferation. Furthermore, re‐epithelialization is dependent on regulated expression of proteases, including plasmin and matrix metalloproteinases, which break down extracellular matrix to allow keratinocyte invasion into wound provisional matrix as well as release and activate matrix‐bound growth factors. Thus, wound re‐epithelialization is a complex process that requires coordinated expression of several new extracellular matrix molecules, their receptors, and proteinases, and when dysregulated, can result in failures to re‐epithelialize and formation of chronic wounds.