Role of mechanical forces and skin tension in scar pathophysiology

Abstract

Scar formation is the natural consequence of wound healing, yet in many cases it leads to hypertrophic scars or keloids that impair function, create aesthetic concerns, and diminish quality of life. While biochemical signaling pathways in wound repair have been well characterized, mechanical forces are now recognized as equally crucial regulators of cutaneous fibrosis. This narrative review utilized a structured literature search of PubMed and Google Scholar databases to evaluate experimental, translational, and clinical evidence regarding the role of mechanical tension and mechanotransduction in wound healing and pathological scar formation. Relevant studies investigating biomechanical signaling pathways, fibroblast activation, extracellular matrix remodeling, and therapeutic tension-modulating strategies were identified through title, abstract, and full-text review. We outline the four phases of wound repair and highlight how aberrant mechanical inputs promote persistent inflammation, fibroblast overactivation, excessive extracellular matrix deposition, and impaired collagen remodeling. Key mechanotransduction pathways, including focal adhesion kinase (FAK)-extracellular signal-regulated kinase (ERK)-monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta (TGF-β)/Smad, platelet-derived growth factor (PDGF)-PI3K/AKT and mitogen-activated protein kinase (MAPK), Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), and Wnt/β-catenin, are discussed with emphasis on their roles in myofibroblast differentiation and fibrosis. Translational advances including stress-shielding devices, force-modulating closure techniques, and topical or intradermal inhibitors of FAK or YAP demonstrate how targeting mechanical pathways can significantly reduce scar formation in animal models and preclinical studies. As mechanical biology continues to intersect with regenerative medicine, therapeutics that modulate tension or interrupt profibrotic mechanotransduction hold promise for shifting cutaneous repair from a fibrotic toward a regenerative, scar-minimizing paradigm.

Keywords

Scar formation / wound healing / mechanical forces / tension / hypertrophic scarring / keloids / fibrogenesis

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