Metformin‐Induced Fibrillation of Copper Formate into Biocompatible Antibacterial Hydrogel for Enhanced Fungal Infection Wound Healing

Abstract The development of copper‐based antibacterial agents with improved biocompatibility and antifungal properties is crucial for combating wound infections. Constructing copper formate hydrogel in the aqueous phase is challenging. Herein, biocompatible antibacterial copper formate‐metformin (Cuf‐MET) hydrogel consists of 3D cross‐linked fibrous network is prepared for the first time using metformin‐induced the fibrillation of copper formate in the aqueous phase. Antibacterial assessment revealed that the Cuf‐MET nanofibers effectively eradicated 99.82% ± 0.47% of E. coli and 98.98% ± 1.25% of S. aureus at a concentration of 0.1 µg mL −1 . When tested against C. albicans , the nanofibers caused a reduction in fungal viability by 85.76% ± 4.64% at a concentration of 500 µg mL −1 . Transmission electron microscopy shows that Cuf‐MET nanofibers disrupt fungal cellular integrity through electrostatic interactions with anionic groups in the cell wall/membrane structures. Cuf‐MET nanofibers induce nuclear and mitochondrial damage via DNA binding mediated structural destabilization. In a C. albicans ‐infected wound model, Cuf‐MET hydrogel treatment enhanced wound closure (93.34%) compared to controls (49.63%), providing a promising foundation for antifungal wound dressings.