Translational approaches manipulating mechanobiology to promote scarless healing in humans

Wound healing is a complex biological process involving hemostasis, inflammation, proliferation, and remodeling. While this orchestrated response is essential for tissue repair, dysregulated healing often culminates in scar formation, characterized by fibrosis and loss of physiological tissue architecture. Scar formation impairs both aesthetic and functional outcomes, posing significant clinical challenges. We previously identified mechanical signaling, specifically through the Focal Adhesion Kinase (FAK) pathway, as a critical regulator of wound healing and fibrosis across various disease states. Elevated mechanical signaling drives fibrosis and scarring, whereas targeted manipulation of this pathway either by device or pharmacologic approaches blocks these adverse effects. We have performed extensive preclinical and clinical studies to demonstrate the potential of these interventions to minimize scarring, promote regenerative healing, and restore dermal architecture. This review highlights the importance of mechanical signaling modulation to achieve scarless healing in humans.