Abstract
Pathological scarring imposes a major clinical and social burden worldwide. Human cutaneous wounds are responsive to mechanical forces and convert mechanical cues to biochemical signals that eventually promote scarring. To understand the mechanotransduction pathways in cutaneous scarring and develop new mechanotherapy approaches to achieve optimal scarring, the current study highlights the mechanical behavior of unwounded and scarred skin as well as intra- and extracellular mechanisms behind keloid and hypertrophic scars. Additionally, the therapeutic interventions that promote optimal scar healing by mechanical means at the molecular, cellular or tissue level are extensively reviewed. The current literature highlights the significant role of fibroblasts in wound contraction and scar formation via differentiation into myofibroblasts. Thus, understanding myofibroblasts and their responses to mechanical loading allows the development of new scar therapeutics. A review of the current clinical and preclinical studies suggests that existing treatment strategies only reduce scarring on a small scale after wound closure and result in poor functional and aesthetic outcomes. Therefore, the perspective of mechanotherapies needs to consider the application of both mechanical forces and biochemical cues to achieve optimal scarring. Moreover, early intervention is critical in wound management; thus, mechanoregulation should be conducted during the healing process to avoid scar maturation. Future studies should either consider combining mechanical loading (pressure) therapies with tension offloading approaches for scar management or developing more effective early therapies based on contraction-blocking biomaterials for the prevention of pathological scarring.