A naringenin-functionalized chitosan/polyphosphate-modified gelatin hydrogel dressing with enhanced antibacterial and antioxidant activities for accelerating infected wound healing.

Designing hydrogel dressings with antibacterial and antioxidant properties is desirable to treat the infected wound. Herein, we developed naringenin-functionalized chitosan (CSN-1 and CSN-2, termed CSNs) combined with polyphosphate-modified gelatin to fabricate hydrogels (CNGP-1 and CNGP-2, termed CNGPs), using CSNs/gelatin hydrogels (CNG-1 and CNG-2, termed CNGs) as controls. All hydrogels exhibited low swelling ratios, high water retention, good biodegradability and excellent biocompatibility. Due to the incorporation of polyphosphate, CNGPs exhibited significantly enhanced mechanical strength, tissue adhesion, and antibacterial activity compared to CNGs. Notably, CNGP-1 demonstrated the best performance, with a compressive strength of 37.79 ± 1.55 kPa, a tissue adhesion strength of 4.21 ± 0.26 kPa, and a nearly 100% inhibition rate against E. coli and S. aureus. Furthermore, CNGPs also possessed potent antioxidant properties, a beneficial characteristic for wound healing. In the infected full-thickness wounds, CNGP-1 treatment achieved a wound closure rate of 71.38 ± 6.65% by day 6, markedly surpassing the control (52.56 ± 4.44%), CNG-1 (61.35 ± 3.33%), and commercial hydrogel dressing (55.52 ± 8.02%) groups. Histological analysis confirmed that CNGP-1 accelerated wound healing by promoting re-epithelialization, granulation tissue formation, skin appendage regeneration, and well-organized collagen deposition. These results indicated that CNGP-1 is a highly promising candidate for advanced wound dressings.