From Chronic Wounds to Scarring: The Growing Health Care Burden of Under- and Over-Healing Wounds

Significance: Wound healing is the largest medical market without an existing small molecule/drug treatment. Both "under-healing" (chronic wounds) and "over-healing" (scarring) cause a substantial biomedical burden and lifelong consequences for patients. These problems cost tens of billions of dollars per year in the United States alone, a number expected to grow as the population ages and the prevalence of common comorbidities (e.g., diabetes) rises. However, no therapies currently exist to produce the "ideal" healing outcome: efficient wound repair through regeneration of normal tissue. Recent Advances: Ongoing research continues to illuminate possible therapeutic avenues for wound healing. By identifying underlying mechanisms of wound repair-for instance, tissue mechanics' role in fibrosis or cell populations that modulate wound healing and scarring-novel molecular targets may be defined. This Advances in Wound Care Forum issue includes reviews of scientific literature and original research from the Hagey Laboratory for Pediatric Regenerative Medicine at Stanford and its alumni, including developing approaches for encouraging wound healing, minimizing fibrosis, and coaxing regeneration. Critical Issues: Wound healing problems reflect an enormous and rapidly expanding clinical burden. The issues of both under- and over-healing wound outcomes will continue to expand as their underlying causes (e.g., diabetes) grow. Targeted treatments are needed to enable wound repair with functional tissue restoration and decreased scarring. Future Directions: Basic scientists will continue to refine understanding of factors driving undesirable wound outcomes. These discoveries are beginning to be translated and, in the coming years, will hopefully form the foundation for antiscarring drugs and other wound therapeutics.