Injectable self-healing dynamic aldehyde-gellan gum-based hydrogel nanocomposite with enhanced antibacterial and antioxidant wound dressing to alleviate chronic skin wound

The difficult-to-heal wounds present a significant challenge for current treatment modalities due to factors such as impaired tissue microenvironments, disrupted inflammatory balance, impaired cellular proliferation, and opportunistic bacterial infections. Drawing inspiration from the biocompatibility of biological macromolecules, we fabricated injectable nanocomposite hydrogels using oxidized gellan gum, gelatin, and polyethyleneimine (PEI). The hydrogels demonstrated remarkable shear-thinning properties due to the reversible imine bonds. The incorporation of quercetin-loaded zein nanoparticles (QZnps) further enhanced the bioactivity of the hydrogels, including improved cell proliferation, antibacterial efficacy, and controlled release of quercetin in vitro. In vivo studies demonstrated that these engineered nanocomposite hydrogels significantly accelerated wound contraction rates in full-thickness wounds in rats. This was achieved through enhanced collagen deposition, optimized re-epithelialization, tissue remodeling, and the restoration of inflammatory balance. These dynamic QZnps-loaded nanocomposite hydrogels offer a promising approach for the treatment of chronic full-thickness wounds, obviating the need for additional antibiotics, traditional drugs, or exogenous cytokines. This versatile hydrogel system holds great potential for the effective management of chronic full-thickness wound healing.