Abstract

Plagued by a prolonged healing process and recurrent bacterial infections, diabetic wounds pose a significant clinical challenge. This underscores the urgent need to develop advanced dressings to address microbial resistance and dysfunctional healing processes. Herein, we present a self-healing double-network hydrogel that integrates antibacterial activity with enhanced tissue regenerative potential, offering a promising strategy to accelerate diabetic wound repair. The hydrogel was constructed by interpenetrating a stable polyacrylamide (PAM) network into a dynamically crosslinked oxidized alginate-polydopamine (OSPB) network. Owing to the multiple dynamic interactions, including ionic chelation, Schiff base coordination, and hydrogen bonding, the hydrogel exhibits intrinsic self-healing behavior. The compact crosslinked double-network architecture imparted reduced swelling and enhanced mechanical strength while maintaining tissue conformity. Its high stretchability, toughness, and rapid recovery under repetitive stress ensured the hydrogel for dynamic wound protection and long-term wound management. To maximize antibacterial potency, the hydrogel incorporates the antimicrobial Jelleine-1 peptide (J-1), which was deposited at the tissue-adhesive interfaces, imparting strong antibacterial activity. Besides, the enhanced transdermal penetration was confirmed using bovine serum albumin - fluorescein isothiocyanate (BSA-FITC) as the macromolecular model. In vivo studies demonstrated an accelerated wound closure with promoted cell proliferation, migration, and angiogenesis, which consequently improves granulation tissue formation and collagen deposition. Collectively, our work presents a multifunctional hydrogel system for promising clinical treatment of diabetic wounds.