Closed-Loop Synergistic Nitric Oxide/Hydrogen Delivery with Feedback Control for Diabetic Wound Healing

Area of Science:

• Biomedical Engineering
• Materials Science
• Regenerative Medicine

Background:

• Dynamic treatment is key to precision medicine, but closed-loop systems responding to biomarkers are difficult to develop.
• Nitric oxide (NO) is a critical biomarker for wound inflammation, necessitating real-time monitoring.
• Current treatments lack adaptive feedback mechanisms for inflammatory conditions.

Purpose of the Study:

• To develop a flexible electrocatalytic system for ultrasensitive, real-time nitric oxide (NO) monitoring.
• To integrate this system into a microneedle array for a closed-loop sensing-feedback-intervention mechanism.
• To enable NO-guided hydrogen generation for precision anti-inflammatory therapy in wound healing.

Main Methods:

• A dual-channel flexible electrocatalytic system (Pd-Ni5P4/DCEFS) was designed and integrated into a microneedle array.
• The system achieved ultrasensitive NO detection (limit of 9.6 nM) and efficient hydrogen evolution reaction.
• A closed-loop strategy was implemented for adaptive, on-demand hydrogen generation based on NO levels.

Main Results:

• The system demonstrated a detection limit of 9.6 nM for NO and a low overpotential for hydrogen evolution (-91.0 mV at -10 mA cm-2).
• In diabetic mouse wound models, the adaptive hydrogen production suppressed inflammation and promoted tissue regeneration.
• Substantial wound closure was achieved within 5 days, with overall healing completed in 11 days.

Conclusions:

• The developed integrated platform establishes a novel closed-loop sensing-feedback-intervention mechanism for dynamic treatment.
• This NO-guided hydrogen generation strategy offers a precision approach to anti-inflammatory therapy for wound healing.
• The study provides a foundation for next-generation self-adaptive therapeutic platforms in regenerative medicine.