Dual-crosslinked self-healing antimicrobial hydrogels with macrophage modulatory activity for accelerated diabetic wound healing.

Persistent inflammation and bacterial infection are the primary reasons for the poor healing of diabetic wounds. In this study, a novel multifunctional hydrogel dressing was fabricated via Schiff base reaction and metal-ligand coordination to precisely regulate the microenvironment of diabetic wounds. Specifically, chitosan was modified with 2,3-epoxypropyltrimethylammonium chloride to obtain quaternized chitosan (QCS). Subsequently, a ternary composite hydrogel system (QCS-PA-Cu2+) was constructed using QCS, protocatechuic aldehyde (PA), and divalent copper ions (Cu2+), which integrated antimicrobial, anti-inflammatory, and wound-healing promotional functions. QCS-PA-Cu2+ hydrogels exhibited short gelation time, high crosslinking density, and low swelling rate, along with stable internal structure and excellent self-healing properties. Furthermore, QCS-PA-Cu2+ hydrogel demonstrated favorable antibacterial activity against Escherichia coli and S. aureus, while showing no obvious cytotoxicity toward mouse fibroblasts. in full-thickness skin defect wound model of diabetic mice,QCS-PA-Cu2+ hydrogel effectively suppressed inflammatory response, promoted the phenotypic conversion of macrophages from the M1 to M2, accelerated collagen deposition, and significantly reduced reactive oxygen species (ROS) production, thereby facilitating wound healing. Collectively, this hydrogel provides a novel strategy for the treatment of diabetic wounds and considerable translational medical value.