All-silk fibroin–based dual-drug delivery system for antibacterial and antioxidant wound repair

Chronic and contaminated wounds are characterized by concurrent bacterial infection and excessive reactive oxygen species (ROS), necessitating biomaterials capable of coordinated antimicrobial and antioxidant regulation. In this study, we developed an all-silk fibroin–based dual-drug delivery system through macromolecular assembly of distinct silk micro/nanostructures. Berberine (BBR) was electrostatically immobilized onto negatively charged silk micro/nanofibers to enable rapid antibacterial release, while curcumin (CUR) was encapsulated within silk fibroin nanoparticles formed via PEG-induced self-assembly to achieve sustained ROS scavenging. The two functional modules were integrated into a porous silk fibroin matrix through lyophilization, yielding a mechanically compliant and structurally interconnected delivery platform. The system exhibited structure-governed staged release behavior, in which electrostatic adsorption enabled rapid BBR diffusion while β-sheet–stabilized hydrophobic confinement regulated sustained CUR transport. In vitro studies demonstrated strong antibacterial activity, effective radical-scavenging capacity, and favorable cytocompatibility. In a full-thickness murine wound model, the optimized formulation accelerated early-stage wound healing and enhanced histological indicators of repair, including improved epithelial continuity and collagen deposition. These results demonstrate how hierarchical silk fibroin organization can couple molecular interaction strength with programmed drug transport, offering a versatile strategy for multifunctional wound-healing biomaterials.