Extreme-Environment Adaptive Hydrogel with Vagus Nerve Modulation for Diabetic Wound Healing and Emotion Management

Chronic diabetic wounds, characterized by persistent inflammation and immune dysregulation, present a significant healing challenge. While traditional hydrogels aid tissue repair, their functionality is often compromised at low temperatures. Herein, we report a polyphenol-mediated conductive hydrogel that remains stable and functional at -80°C. Engineered from casein, dopamine-modified poly(3,4-ethylenedioxythiophene), and a synergistic antifreeze system (dopamine, gluten, glycerol), the hydrogel maintains its conductivity, bioactivity, and therapeutic efficacy after freezing. The hydrogel functions both as a therapeutic dressing and a bioelectronic interface. When coupled with vagus nerve stimulation (VNS), the hydrogel synergistically accelerates full-thickness wound healing by regulating inflammation, scavenging ROS, promoting macrophage M2 polarization, and enhancing angiogenesis. Its remarkable cryo-stability is attributed to polyphenol-mediated water confinement and cryoprotective gluten micelles. Concurrently, the hydrogel facilitates real-time ECG, EMG, and EEG monitoring and enables VNS-driven modulation of EEG-α waves to alleviate depressive-like behavior. This integrated system presents a novel therapeutic paradigm for managing both the physiological and psychological complications of diabetes, even under extreme environmental conditions.