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 Cu²⁺ to strengthen the mechanical strength followed by encapsulating mussel adhesive protein (MAP) as composite dressings. Intriguingly, CG-Cu²⁺ _0.5-DG₁₀ possessed proper rheological properties and mechanical strength predominantly driven by strong CG-H₂O-Cu²⁺ and Cu²⁺-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 Cu²⁺ within 48 h. The incorporation of MAP further loosened the tight crosslinking of CG-Cu²⁺ _0.5-DG_10. The screened CG-Cu²⁺ _0.5-DG₁₀/MAP possessed excellent self-healing, injectability, antibacterial, anti-inflammatory, cell proliferation-promotion activities with high biocompatibility. Therefore, CG-Cu²⁺ _0.5-DG₁₀/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 Cu²⁺-inspired hydrogels for the management of burns and infected wounds.

Keywords: composite hydrogel; copper ion; dipotassium glycyrrhizinate; dual controllable release; hydrogen bond interaction; wound and burn healing.