Wound healing under the regulation of mechanically active biomaterials: From mechanism exploration to scar prevention

Severe cutaneous injury predictably culminates in scar formation, typified by the loss of skin appendages and a consequent impairment of both structural integrity and physiological function. A growing body of evidence now indicates that mechanical cues are as determinative as biochemical signals in directing cutaneous repair and scar formation. Accordingly, mechanomodulatory biomaterials have emerged as promising platforms for promoting scar-free wound repair. However, the mechanistic bases by which mechanical forces remodel the extracellular milieu-and how such forces can be rationally exploited to reprogram mechanotransductive signaling-remain incompletely resolved. This knowledge gap poses a major barrier to the clinical translation of mechanotherapeutic approaches. In this review, we synthesize current understanding of cutaneous biomechanics and its intimate interplay with wound-healing cascades, and we delineate the principal mechanotransduction pathways that convert physical stimuli into cellular fate decisions. We further provide a critical appraisal of recent advances in mechanically active dressings designed to deliver spatially and temporally controlled mechanical cues that bias tissue repair toward regeneration. Finally, we identify outstanding challenges and propose future directions for the development of mechanoregulated biomaterials, offering a strategic roadmap to accelerate the translation of scarless healing strategies into clinical practice.