Bioactive eggshell membrane-integrated nanofiber dressing with mesoporous polydopamine-mediated sustained dexamethasone delivery for enhanced wound regeneration.

Wound healing is often impeded by excessive inflammation and oxidative stress, necessitating multifunctional dressings with therapeutic and regenerative properties. Here, a biodegradable nanofiber dressing (PE@MD) composed of poly(L-lactide-co-ε-caprolactone) (PLCL), water-soluble eggshell membrane (ESM), and dexamethasone (DEX)-loaded mesoporous polydopamine nanoparticles (MPDA) was developed via electrospinning technology. Proteomic and metabolomic analyses revealed that ESM contains abundant proteins and metabolites associated with cytoskeletal organization, antioxidation, and modulation of inflammation, providing intrinsic bioactivity to the composite. The incorporation of MPDA enabled sustained and controlled DEX release while enhancing the ROS scavenging capacity. The optimized PE@MD nanofibers exhibited good flexibility, biocompatibility, and degradation properties. In vitro, the dressing promoted the migration of fibroblasts and endothelial cells, reduced ROS levels, and induced macrophage polarization toward the M2 phenotype through NF-κB inhibition. Transcriptomic analysis confirmed activation of antioxidant and extracellular matrix remodeling pathways. The PE@MD significantly accelerated wound closure, re-epithelialization, and collagen deposition while reducing COX-2, IL-1β, MPO, and NF-κB p65 expression in a rat full-thickness wound model. These findings demonstrate that the PE@MD dressing effectively integrates bioactive ESM and MPDA-mediated sustained drug release, providing a sustainable and multifunctional platform that promotes enhanced collagen deposition, accelerated re-epithelialization, and reduced inflammatory infiltration during skin repair.