Dynamic Mechanical Stimulation of Fibroblasts in Aligned Scaffolds: Inhibiting the YAP/TAZ Pathway to Reduce Wound Contraction

Pathological scarring and wound contraction remain significant medical challenges, often resulting in functional impairment, loss of mobility, and aesthetic distress(1,2). Adult wound healing usually ends with fibrotic scars and disorganized collagen. In contrast, fetal healing happens without scarring. Why? Because fetal skin has a low-tension environment and special fibroblast lineages(3,4). Central to this biophysical regulation is the YAP/TAZ signaling pathway, a mechanosensitive molecular rheostat that senses matrix stiffness and tension to drive the myofibroblast phenotype(5,6,7). This review examines recent advancements in the synergistic use of aligned scaffold architectures and dynamic mechanical stimulation to guide cellular recruitment and maturation(8,9,10). Furthermore, we explore therapeutic strategies to inhibit the YAP/TAZ pathway—ranging from pharmacological agents like Verteporfin to "smart" drug-delivery nanogels—to interrupt the fibrotic feedback loop and steer the healing process toward functional skin regeneration(11,12,13).