Probiotic-Enabled Conductive Alginate Hydrogel with CeO2 Nanozymes and Electrical Stimulation for Synergistic Diabetic Wound Healing

Abstract Diabetic wounds feature sustained hyperglycemia, intense oxidative stress, frequent bacterial invasion and compromised angiogenic activity. These factors jointly form a pathological microenvironment that hinders routine therapeutic interventions. Current dressings typically address only one or two of these barriers, leaving the complex interplay of redox imbalance, infection, and bioelectrical dysfunction insufficiently tackled. Herein, we report a probiotic-enabled conductive alginate double-network hydrogel embedded with CeO2 nanozymes (SAMCL) that integrates redox regulation, microecological intervention, and bioelectrical support within a single platform. The CeO2 efficiently scavenge reactive oxygen species and generate oxygen, while metabolically active Limosilactobacillusreuteri produces reuterin, endowing the hydrogel with potent broad-spectrum antibacterial and antibiofilm activities. The hydrogel retains recoverable ionic conductivity, enabling electrical stimulation to further promote macrophage M2 polarization and angiogenesis. In a diabetic mouse infected wound model, the SAMCL hydrogel with electrical stimulation achieved near-complete wound closure on day 14, with regenerated cutaneous follicles and glandular tissues, reduced inflammation, and normalized hypoxic signaling. This study develops a feasible approach to modulate the microenvironment of diabetic wounds, and lays a foundation for the clinical translation of multifunctional chronic wound dressings.