Poison Turned\nPanacea: Arsenic Trioxide Loaded Hydrogel\nfor Inhibiting Scar Formation in Wound Healing

Without intervention, the natural wound healing process\ncan often\nresult in scarring, which can have detrimental effects on both the\nphysical and mental well-being of patients. Therefore, it is crucial\nto develop biomaterials that can promote healing without scarring.\nRegulating the Yes-associated protein-1/PDZ-binding motif (YAP/TAZ)\nsignaling pathway is possible to reduce excessive fibrosis of fibroblasts\nand proliferation of vascular endothelial cells, ultimately impacting\nscar formation. Arsenic trioxide (ATO), an ancient drug with medicinal\nand toxic properties, has shown promise in regulating this pathway.\nAn ATO-loaded hydrogel dressing (ATO@CS/SA) was created to facilitate\nscarless wound healing, utilizing chitosan (CS) and sodium alginate\n(SA) to prevent direct contact of ATO with the wound tissue and minimize\npotential side effects. In vitro studies demonstrated that low concentrations\nof ATO did not impact cell viability and even promoted proliferation\nand migration. Co-culturing the hydrogel with fibroblasts and vascular\nendothelial cells led to decreased expression levels of YAP and TAZ.\nAnimal studies over a 90-day period revealed significant inhibition\nof scar formation with this system. Histological experiments further\nconfirmed that the decreased expression of YAP and TAZ was responsible\nfor this outcome. In conclusion, when administered at the appropriate\ndose, ATO can be repurposed from a traditional poison to a therapeutic\nagent, effectively suppressing excessive cell fibrosis and blood vessel\nproliferation and offering a novel approach to scar-free treatment.