MXene-zingerone synergized gelatin-based hydrogel for accelerated open wound healing and epidermal regeneration in a preclinical model

The treatment of open wounds presents a significant challenge in clinical practice due to the increased risk of bacterial infections and prolonged recovery times. Currently, antibiotics are highly preferred to address underlying problems; however, their misuse has led to antibacterial resistance and compromised biocompatibility. This underscores the need for an advanced biological macromolecule-based system with multifunctional properties. Herein, we report a gelatin-based hydrogel dressing integrated with MXene and zingerone (GPM Z) to manage open wounds. Nanocomposite hydrogels demonstrated porous networks, hydrophilic nature, and rheological behavior, ensuring their reliability in a physiological environment. The sustained release of zingerone from hydrogels promotes prolonged therapeutic effects while minimizing side effects associated with burst release. In vitro analysis confirms >80 % antioxidant potential as determined by DPPH assay, hemolysis (<5 %), n-HDF cells compatibility, and antibacterial activity of nanocomposite hydrogels, which can be tuned by varying MXene concentration in hydrogels. In vivo analysis highlights the effectiveness of GPM-5 Z hydrogel in facilitating wound closure (98.75 % by day 14). The synergistic interplay of MXene and zingerone enhances wound healing by combining MXene antibacterial potential and bio interactive surface supporting cell proliferation with zingerone antioxidant activity that mitigates oxidative stress, thereby facilitating collagen deposition, re-epithelialization, and angiogenesis.