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

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Bioelectronics

Background:

• Chronic diabetic wounds exhibit inflammation and immune dysregulation, hindering healing.
• Conventional hydrogels lose functionality at low temperatures, limiting their therapeutic applications.
• A need exists for advanced wound dressings that are stable and effective in diverse conditions.

Purpose of the Study:

• To develop a cryo-stable, conductive hydrogel for diabetic wound healing.
• To investigate the hydrogel's efficacy as a therapeutic dressing and bioelectronic interface.
• To evaluate the synergistic effects of the hydrogel with vagus nerve stimulation (VNS).

Main Methods:

• Fabrication of a polyphenol-mediated hydrogel using casein, dopamine-modified poly(3,4-ethylenedioxythiophene), and an antifreeze system.
• Assessment of hydrogel stability and functionality after freezing at -80°C.
• In vivo evaluation of wound healing acceleration with and without VNS, including monitoring of inflammation, oxidative stress, macrophage polarization, and angiogenesis.
• Integration of the hydrogel for real-time physiological monitoring (ECG, EMG, EEG) and VNS-driven neuromodulation.

Main Results:

• The engineered hydrogel demonstrated remarkable cryo-stability, maintaining conductivity, bioactivity, and therapeutic efficacy post-freezing.
• Combined hydrogel therapy and VNS synergistically accelerated full-thickness wound healing by modulating inflammation, reducing ROS, promoting M2 macrophage polarization, and enhancing angiogenesis.
• The hydrogel successfully facilitated real-time physiological monitoring and VNS-induced EEG-α wave modulation, alleviating depressive-like behaviors.
• Polyphenol-mediated water confinement and gluten micelles were identified as key factors for cryo-stability.

Conclusions:

• The developed polyphenol-mediated conductive hydrogel offers a robust solution for treating chronic diabetic wounds, even under extreme cold conditions.
• This integrated system provides a dual therapeutic and bioelectronic approach, addressing both the physical and psychological aspects of diabetes complications.
• The cryo-stable hydrogel represents a significant advancement in regenerative medicine and bioelectronic interfaces for challenging clinical scenarios.