epithelialization

Epithelialization is the process by which epithelial cells regenerate to restore the epidermal barrier after skin or mucosal injury. It is a key component of wound healing that proceeds alongside inflammation, tissue formation, and remodeling.

Keratinocytes at the wound margin become activated and migrate as cohesive sheets over a provisional matrix, often provided by fibrin and plasma proteins. Migration is guided by the re-forming basement membrane and by signaling from dermal fibroblasts and inflammatory cells. Keratinocytes proliferate in the basal layer to replace lost cells and then stratify to restore the layered epidermis. Adhesion molecules such as integrins and cadherins, and remodeling enzymes such as matrix metalloproteinases, coordinate movement and matrix turnover. As closure proceeds, the basement membrane is re-established and the epidermis regains its normal architecture. Re-epithelialization ends when a continuous, stratified epithelium covers the wound bed, restoring barrier function and reducing fluid loss and infection risk.

The rate and success of epithelialization depend on wound size and depth, perfusion, infection, moisture balance, mechanical stability, and systemic factors such as age, diabetes, malnutrition, and steroid use. In larger wounds, epithelialization can also be aided by cells from skin appendages like hair follicles and sweat glands. It is distinct from angiogenesis and wound contraction and is most active during the proliferative phase, influenced by growth factors such as EGF, FGF, KGF, and TGF-β as well as the extracellular matrix environment. Impaired epithelialization contributes to chronic wounds and is a common target in wound care strategies.