Hypertrophic Scarring and Keloids: Epidemiology, Molecular Pathogenesis, and Therapeutic Interventions

Abstract

Wound healing is a complex, multicellular process that is essential for restoring tissue integrity after injury. In a subset of individuals, however, this process becomes dysregulated, culminating in hypertrophic scars or keloids—fibroproliferative disorders marked by excessive extracellular matrix deposition and prolonged inflammation. Although these lesions differ clinically, both share overlapping molecular mechanisms involving aberrant activation of the TGF-β, Intergrin-FAK, and Wnt/β-catenin pathways. Recent insights from single-cell and multiomics technologies have revealed profound heterogeneity within scar-forming fibroblast populations and highlighted the modulatory roles of immune cells, genetic predispositions, and anatomical tension. However, despite increasing mechanistic understanding, current interventions—including surgery, corticosteroids, and laser therapy—are limited by high recurrence rates and variable efficacy. Emerging strategies now target fibroblast plasticity, inflammatory circuits, and biomechanical feedback via tools such as gene editing, immune modulation, and smart biomaterials. This review integrates advances across epidemiology, molecular signaling, and therapeutic innovation, underscoring the need for personalized, multitargeted approaches. Ultimately, transforming pathological scarring from a persistent clinical burden into a regenerative opportunity will depend on interdisciplinary collaboration and the continued translation of benchside discovery into bedside care.