Copper Ion‐Inspired Dual Controllable Drug Release Hydrogels for Wound Management: Driven by Hydrogen Bonds

Abstract Bacterial infections and inflammation progression yield huge trouble for the management of serious skin wounds and burns. However, some hydrogel dressing exhibit poor wound‐healing capabilities. Additionally, little information is given on the molecular theory of hydrogel gelation mechanisms and drug release performance from drug‐polymer network in the water environment. Herein, cationic guar gum (CG) is first mixed with dipotassium glycyrrhizinate (DG), and then crosslinked Cu 2+ to strengthen the mechanical strength followed by encapsulating mussel adhesive protein (MAP) as composite dressings. Intriguingly, CG‐Cu 2+ 0.5 ‐DG 10 possessed proper rheological properties and mechanical strength predominantly driven by strong CG‐H 2 O‐Cu 2+ and Cu 2+ ‐CG hydrogen bonding interaction. Weak DG‐CG hydrogen bonding only controlled DG release in the initial 4 h, while strong hydrogen bonding is the main force regulating the sustained release of Cu 2+ within 48 h. The incorporation of MAP further loosened the tight crosslinking of CG‐Cu 2+ 0.5 ‐DG 10. The screened CG‐Cu 2+ 0.5 ‐DG 10 /MAP possessed excellent self‐healing, injectability, antibacterial, anti‐inflammatory, cell proliferation‐promotion activities with high biocompatibility. Therefore, CG‐Cu 2+ 0.5 ‐DG 10 /MAP hydrogel expedited wound closure on S. aureus ‐infected full‐thickness skin wound model and lowered necrosis progression to the unburned interspaces on a rat burn model. The results highlight the promising translational potential of Cu 2+ ‐inspired hydrogels for the management of burns and infected wounds.