Topical Application of TT-10 Ameliorates Impaired Wound Healing

BACKGROUND: In recent decades, chronic wounds have become an increasingly significant clinical concern because of their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of reepithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, the authors have identified the pharmacologic product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds. METHODS: The role of TT-10 in regulating YAP activity and subcellular localization was determined by Western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination; hematoxylin and eosin staining; and measuring wound areas and gaps in normal, diabetic, and ischemic wounds. RESULTS: The authors' findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, the authors showed that intracutaneous injection of TT-10 along the wound periphery promoted reepithelialization by means of YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models. CONCLUSION: The authors' research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair. CLINICAL RELEVANCE STATEMENT: The authors' research identifies TT-10, a small molecule YAP activator, as a novel therapeutic candidate that enhances keratinocyte function and promotes reepithelialization, offering plastic surgeons an innovative approach to addressing chronic wound challenges.