This study presents the development and comprehensive evaluation of a phloretin-loaded graphene oxide-infused self-healing foam dressing for enhanced wound healing. Phloretin (PHL), a polyphenolic compound known for its antioxidant, anti-inflammatory and antibacterial properties was encapsulated with β-cyclodextrin (PHL-β-CYD) to improve its aqueous solubility and stability. This inclusion complex (IC) was characterized using FTIR, XRD, FESEM, TGA, and DTA to confirm its structural integration, changes in crystallinity, and thermal behavior. Foam dressings were fabricated using an optimized blend of chitosan and sodium alginate, with graphene oxide as a self-healing agent. The PHL-β-CYD inclusion complex was incorporated into the foam matrix at varying concentrations of F1 (0.25%), F2 (0.5%), and F3 (1%), and evaluated for swelling behavior, in vitro drug release, self-healing, hemocompatibility, blood coagulation, and antibacterial and anti-inflammatory potential. Among the formulations, FD-2 (0.5% PHL-β-CYD) was selected for further evaluation based on its optimal swelling behavior and sustained in vitro release profile. Drug release kinetics indicated sustained and pH-responsive behavior, while hemolysis and coagulation assays confirmed excellent biocompatibility and pro-coagulant properties. Anti-inflammatory activity was validated through BSA and egg albumin denaturation assays. In vitro cytotoxicity was conducted using fibroblast L929 cell lines and in vivo wound-healing efficacy were evaluated using an excision wound model in mice, with histopathological analysis confirming enhanced epithelialization and collagen deposition in treated group. Along with that, a network pharmacological approach was employed to identify the overlapping molecular targets between phloretin and wound-associated genes. Protein–protein interaction analysis, and GO-KEGG pathway enrichment, highlighted key biological processes and molecular pathways, particularly those involved in inflammation and tissue regeneration. In conclusion, the results validate the therapeutic potential of the developed PHL-loaded foam dressing as a multifunctional dressing for wound management and skin tissue repair.
Graphical abstract
Fabrication of a phloretin-loaded, graphene oxide-infused self-healing foam dressing using a sodium alginate-chitosan polymeric blend for enhanced wound healing. The optimized formulation (FD-2) exhibited sustained drug release, biocompatibility, antibacterial and anti-inflammatory activity. In vitro and in vivo studies confirmed accelerated wound healing and tissue regeneration. Network pharmacology analysis provided mechanistic insights into phloretin’s ability in modulating key inflammatory pathways