Re-epithelialization of adult skin wounds: Cellular mechanisms and therapeutic strategies

Cutaneous wound healing in adult mammals is a complex multi-step process involving overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodelling. Re-epithelialization describes the resurfacing of a wound with new epithelium. The cellular and molecular processes involved in the initiation, maintenance, and completion of epithelialization are essential for successful wound closure. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components. Here, we focus on cellular mechanisms underlying keratinocyte migration and proliferation during epidermal closure. Inability to re-epithelialize is a clear indicator of chronic non-healing wounds, which fail to proceed through the normal phases of wound healing in an orderly and timely manner. This review summarizes the current knowledge regarding the management and treatment of acute and chronic wounds, with a focus on re-epithelialization, offering some insights into novel future therapies.