Healing Mechanisms in Cutaneous Wounds: Tipping the Balance

Acute and chronic cutaneous wounds pose a significant health and economic burden. Cutaneous wound healing is a complex process that occurs in four distinct, yet overlapping, highly coordinated stages: hemostasis, inflammation, proliferation, and remodeling. Postnatal wound healing is reparative, which can lead to the formation of scar tissue. Regenerative wound healing occurs during fetal development and in restricted postnatal tissues. This process can restore the wound to an uninjured state by producing new skin cells from stem cell reservoirs, resulting in healing with minimal or no scarring. Focusing on the pathophysiology of acute burn wounds, this review highlights reparative and regenerative healing mechanisms (including the role of cells, signaling molecules, and the extracellular matrix) and discusses how components of regenerative healing are being used to drive the development of novel approaches and therapeutics aimed at improving clinical outcomes. Important components of regenerative healing, such as stem cells, growth factors, and decellularized dermal matrices, are all being evaluated to recapitulate more closely the natural regenerative healing process. Impact Statement Acute wounds from thermal injury are common; they exert substantial physical and psychological effects on a patient and result in significant morbidity and mortality. This review provides a detailed overview of the mechanisms of reparative and regenerative wound healing; discusses the key cell types, signaling molecules, and molecular targets that influence these important biological pathways; and highlights current therapeutic approaches aimed at promoting regenerative wound healing. An increased understanding of the underlying mechanisms of reparative and regenerative healing will contribute to the development of innovative strategies for the clinical treatment of patients with severe burns.