Subcutaneous Fascial Microenvironment in Skin Scar Formation: Mechanisms and Therapeutic Strategies

Subcutaneous fascia has attracted increasing attention as a possible contributor to deep cutaneous wound repair. Murine lineage‐tracing and skin–fascia chimera studies suggest that fascia‐associated fibroblasts and pre‐existing extracellular matrix can be mobilized into the wound bed, where they contribute to matrix deposition and wound contraction. How far these findings apply to human pathological scars, however, remains uncertain. Hypertrophic scars and keloids are distinct disorders, and their development reflects the combined effects of mechanical tension, persistent inflammation, endothelial dysfunction, fibroblast heterogeneity, genetic susceptibility, and anatomical site. At present, there is no direct evidence that fascia‐derived fibroblasts are the main cellular source of human keloids. In this review, we examine the evidence for fascia involvement alongside the broader literature on human scar biology. We also discuss several fascia‐related therapeutic targets, including retinoic acid signaling, HIF‐1α, p120‐catenin, N‐cadherin, and connexin 43. Most of these approaches are supported mainly by cell and animal studies, and their clinical value remains to be established. Fascia is therefore best viewed as one context‐dependent component of scar formation rather than a universal explanation for pathological scarring.