Ta-Modified Hydrogel Reduces Flap Necrosis By Inhibiting Ferroptosis

To address ferroptosis-driven orofacial flap necrosis, this project developed a multifunctional hydrogel combining wet adhesion, antibacterial properties, and iron-scavenging capabilities. HD hydrogels were synthesized through EDC/NHS-mediated crosslinking of hyaluronic acid (HA) and dopamine (DA), demonstrating robust wet adhesion and mechanical flexibility. Functionalization with tannic acid (TA) further enhanced adhesion strength while introducing iron-chelating and antimicrobial capabilities. Mechanical properties were analyzed using Tensile tests, Rheometry, and Adhesion measurements. Iron adsorption capacity was determined by SEM and EDS. Antibacterial performance assessed through inhibition zone and live/dead staining against S. aureus, E. Coli and S. mutans. A BALB/c mouse ischemic skin flap model (1×2.5 cm, n=5/group) was used to evaluate flap survival (postoperative days 3, 5, 7), histological repair (HE/Masson staining), and iron accumulation (Prussian blue staining), with all animal procedures conducted in compliance with ethical guidelines for experimental research. HD-TA hydrogel exhibited strong wet adhesion (61.2kPa), efficient iron chelation (73.6%), and broad antimicrobial efficacy (87.2–94.3% inhibition).In vivo treatment significantly improved flap survival rates (93.3 ± 3.8% vs. 58.7 ± 4.5% in controls, p < 0.001) with improved histological regeneration, including increased neovascularization and collagen deposition along with reduced inflammatory infiltration. This TA-modified hydrogel establishes a dual-action therapy targeting ferroptosis and bacterial infection for enhanced flap recovery.