Significance: Hypertrophic scars (HTS) are a fibroproliferative disorder that occur following deep dermal injury and affect up to 72% of burn patients. These scars result in discomfort, impaired mobility, disruption of normal function and cosmesis, and significant psychological distress. Currently, there are no satisfactory methods to treat or prevent HTS, as the cellular and molecular mechanisms are complex and incompletely understood. This review summarizes the biology of proteins in the dermal extracellular matrix (ECM), which are involved in wound healing and hypertrophic scarring. Recent Advances: New basic research continues toward understanding the diversity of cellular and molecular mechanisms of normal wound healing and hypertrophic scarring. Broadening the understanding of these mechanisms creates insight into novel methods for preventing and treating HTS. Critical Issues: Although there is an abundance of research conducted on collagen in the ECM and its relationship to HTS, there is a significant gap in understanding the role of proteoglycans and their specific isoforms in dermal fibrosis. Future Directions: Exploring the biological roles of ECM proteins and their unique isoforms in HTS, mature scars, and normal skin will further the understanding of abnormal wound healing and create a more robust understanding of what constitutes dermal fibrosis. Research into the biological roles of ECM protein isoforms and their regulation during wound healing warrants a more extensive investigation to identify their distinct biological functions in cellular processes and outcomes.
Keywords: Extracellular matrix proteins; hypertrophic scars; proteoglycans and their isoforms.