Almond Gum/Gelatin-Based Multifunctional Nanocomposite Hydrogel: A Synergistic Hybrid Platform for Wound Healing

Management of wounds unveils various crucial clinical constraints, emphasizing the demand for transformed wound dressings that maximize the healing process and facilitate tissue regeneration. Here, a simple, green yet scalable approach was established to fabricate a multifunctional nanocomposite hydrogel employing plant- and animal-derived polymers, specifically almond gum and gelatin, enhanced with bioactive L-menthol and Ae-ZnONPs (MeZ@ALGEL), to improve wound healing by reinforcing the wound environment with its bactericidal, reactive oxygen species (ROS) regulation, and tissue regeneration abilities. MeZ@ALGEL exhibits necessary physicochemical and mechanical properties and significant antibacterial and antioxidant activities, making it ideal for topical administration and beneficial in accelerating wound repair. Under in vitro conditions, MeZ@ALGEL demonstrates a high degree of biocompatibility with fibroblast cells, actively promotes their migration in wound-like cases, and indicates improved hydroxyproline content with upregulation of <i>Col-1</i>, <i>Col-3</i>, <i>Vegf</i> genes, and downregulation of the <i>Il-1b</i> gene revealed in gene expression analysis. In vivo studies using <i>Caenorhabditis elegans</i> as a preliminary wound model reveal that the MeZ@ALGEL hydrogel is nontoxic up to the concentration of 125 μg/mL, promotes healing of glass wool-mediated wounds, exhibits strong antimicrobial activity, and accelerates wound repair through a multifaceted approach involving bacterial eradication, regulation of ROS, and stimulation of collagen synthesis, ultimately enhancing wound healing in the model organism. By these findings, the facilely synthesized nanocomposite hydrogel opens up the possibilities for developing multifunctional hydrogels of natural origin by utilizing the synergistic interaction of components and offers great potential in the wound care sector.