A Paradigm of Fibroblast Activation and Dermal Wound Contraction to Guide the Development of Therapies for Chronic Wounds and Pathologic Scars

Significance: Delayed wound healing and pathologic scarring are abnormal processes that can be thought of as occurring on a wound healing continuum, where insufficient wound contraction leads to nonhealing wounds, and overexuberant wound contraction leads to scarring. Chronic nonhealing wounds, including diabetic foot wounds, decubitus ulcers, and venous stasis ulcers, affect millions of people annually in the United States and costs billions of dollars. Similarly, pathologic scaring affects more than 40 million Americans annually and also costs billions of dollars. Critical Issues: While there are multiple factors that contribute to chronic nonhealing wounds and pathologic scars, a derangement in wound contraction is common to both. In this article, we will present a paradigm of dermal wound contraction, derived from clinical observations and basic science evidence, which pertains to chronic nonhealing wounds and pathologic scars. Recent Advances: We will review how select therapies currently under investigation and in development fit the paradigm. Future Directions: The paradigm will facilitate translational research and enable the development of future innovative therapies.