Carbohydrate polymer-stabilized Pickering emulsion gel coordinates antimicrobial and pro-regenerative cues for...

Advanced wound dressings capable of coordinating antimicrobial, anti-inflammatory, and pro-regenerative functions remain highly desirable for scar-minimized skin repair. Herein, we developed a carbohydrate polymer-stabilized Pickering emulsion gel (Ag@FO-PGEL) by integrating glycyrrhizic acid (GA) fibrillar networks with silver-loaded γ-cyclodextrin frameworks (Ag@CDF) for controlled topical delivery of frankincense oil (FO) and silver ions (Ag⁺). The carbohydrate-driven interfacial architecture enabled stable emulsion gel formation with uniform particle distribution and sustained Ag⁺ release over 30 days, characterized by an initial burst release (45% within 12 h) followed by prolonged diffusion-controlled release. The resulting Ag@FO-PGEL exhibited favorable rheological behavior, long-term colloidal stability, broad-spectrum antibacterial activity, and good cytocompatibility. In vivo, Ag@FO-PGEL accelerated wound closure to 99.6% by day 14 while promoting collagen remodeling, angiogenesis, and reduced inflammatory infiltration. Mechanistically, the formulation modulated macrophage polarization toward a pro-regenerative phenotype and biphasically regulated senescence-associated markers: early p16 suppression to support proliferation followed by p16/p53 activation to limit fibrosis. The synergistic integration of GA fibrillar assembly and porous γ-cyclodextrin framework stabilization provides a multifunctional carbohydrate-based platform for localized and sustained wound therapy. These findings highlight the potential of carbohydrate-engineered Pickering emulsion gels as biofunctional wound dressings for regenerative skin repair.