Chaoyang Huang, Lianglong Chen, Huihui Zhang, Bo Liu, Haiyan Zhou, Ying-Cheng Chen, Xian Li, Xiaoyang Liu, Limin Zhao, Xue Wang, Mian Wu, Shuaijie Li, Dan Yi, Chunyu Liu, Haobo Pan, Lei Yang
Recalcitrant wounds, such as diabetic foot ulcers (DFUs), pose a significant challenge to current therapeutic options due to persistent exudate, high infection risk, and a complex pathological microenvironment. This necessitates a novel dressing that can simultaneously provide both a physical barrier and active biological intervention. Inspired by the feathers of waterfowl, we developed a hierarchically engineered Janus dressing (PPT@PG-BG) via electrospinning, which integrates a hydrophobic antibacterial outer layer with a hydrophilic inner layer for the spatiotemporally controlled release of therapeutic ions (Mg 2+ , Zn 2+ , and Ce 3+ ). This "external defense and internal regulation" strategy effectively re-establishes immune-angiogenic homeostasis by activating the p-ERK/Nrf2 antioxidant pathway, promoting M2 macrophage polarization, and enhancing neovascularization, ultimately achieving accelerated wound healing (97.85% closure) in a diabetic infected wound model. In summary, this Janus dressing, which combines a simple fabrication process with integrated physical protection and multi-ion synergistic biotherapy, provides an effective strategy with significant clinical translation potential for treating complex, hard-to-heal wounds and promises to substantially improve patient outcomes. • A feather-inspired Janus fibrous construct (PPT@PG-BG) is engineered by integrating biomimetic topographical architecture with programmable ionic microenvironment modulation, enabling spatiotemporally coordinated intervention for chronic diabetic wound repair. • The superhydrophobic outer layer functions as a multifunctional barrier, effectively inhibiting microbial adhesion and biofilm development through synergistic physical shielding, wettability control, and sustained antibacterial activity. • The bioactive inner layer dynamically reconstructs the pathological wound microenvironment by releasing therapeutic ions, thereby mitigating oxidative stress, modulating inflammation, and promoting angiogenesis to accelerate tissue regeneration. Significance: This bilayer “external protection-internal regulation” dressing combines an antimicrobial barrier with spatiotemporal ion programming to prevent infection and promote diabetic wound healing, offering a novel and promising solution for complex wound repair.