Coenzyme-based elastomeric adhesive patch as iron ion capturer to regulate iron metabolism for diabetic oral ulcer repair

Iron metabolism imbalance under high-glucose and nutrient-rich conditions is a key factor inhibiting the healing of diabetic oral ulcers. This study confirms the extensive iron accumulation and ferroptosis occurrence in diabetic oral ulcers. To address this, an oral patch (PLTP) is designed by combining two natural bioactive molecules of lipoic acid (LA) and tea polyphenols (TP). The abundant carboxyl and hydroxyl groups in PLTP act as iron ion capturers, adsorbing extracellular iron, reducing iron transport into cells, and effectively cutting off the iron source for intracellular ferroptosis. The in-situ release of LA and TP at wound site not only aids in restoring intercellular iron homeostasis via regulating the intracellular Xc^-/GPX4 axis, enhancing antioxidant capacity, upregulating the expression of SLC40A1, and downregulating the expression of DMT1, but also modulates the immune microenvironment, further supporting wound healing. In addition, PLTP exhibits a robust adhesion strength of 14.32 kPa to oral mucosa even after 24 h of vigorous stirring in an iron-rich solution <i>in vitro</i>, and maintains prolonged adhesion in the moist and dynamic oral cavity for over 24 h <i>in vivo</i>. This effectively protects ulcer sites from bacterial invasion and food debris contamination. <i>In vivo</i> experiments show that PLTP significantly accelerates diabetic oral ulcer healing, achieving 92.4 % wound closure by day 8, outperforming both commercial chitosan patches (53.7 %) and the anti-ferroptosis drug Deferasirox (60.0 %). The underlying mechanisms and therapeutic effects of PLTP are further systematically validated <i>in vivo</i>, hoping to provide new insights into iron metabolism regulation for tissue repair in diabetes.