Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions

Abstract

Venous leg ulcers, diabetic foot ulcers, and pressure ulcers are complex chronic wounds with multifactorial etiologies that are associated with high patient morbidity and mortality. Despite considerable progress in deciphering the pathologies of chronic wounds using "omics" approaches, considerable gaps in knowledge remain, and current therapies are often not efficacious. We provide a comprehensive overview of current understanding of the molecular mechanisms that impair healing and current knowledge on cell-specific dysregulation including keratinocytes, fibroblasts, immune cells, endothelial cells and their contributions to impaired reepithelialization, inflammation, angiogenesis, and tissue remodeling that characterize chronic wounds. We also provide a rationale for further elucidation of ulcer-specific pathologic processes that can be therapeutically targeted to shift chronic nonhealing to acute healing wounds.

Figure 1.

“Omics” approaches to therapeutic targeting of chronic ulcers. Comparative “omics” and bioinformatics analyses can be used to decipher pathophysiologic mechanisms that drive chronic wound pathology and to identify biomarkers and novel therapies likely to heal chronic wounds. (DFU) Diabetic foot ulcer, (VLU) venous leg ulcer, (PU) pressure ulcer.