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

Dynamic treatment represents the cornerstone of precision medicine. However, the development of closed-loop systems that respond to endogenous biomarkers remains challenging. Here, we report a dual-channel flexible electrocatalytic system (Pd-Ni₅P₄/DCEFS) integrated into a microneedle array that enables ultrasensitive real-time monitoring of nitric oxide (NO)-a key biomarker of wound inflammation-with a detection limit of 9.6 nM, while simultaneously driving the hydrogen evolution reaction with a low overpotential of - 91.0 mV at - 10 mA cm^-2. This integrated platform establishes a closed-loop sensing-feedback-intervention mechanism, enabling NO-guided on-demand hydrogen generation for precision anti-inflammatory treatment. In diabetic mouse skin wound models, this adaptive hydrogen production strategy markedly suppresses inflammation, promotes tissue regeneration, achieves substantial wound closure within 5 days, and reduces the overall healing time to 11 days. This study establishes a new paradigm for closed-loop dynamic treatment of inflammatory diseases and provides a critical foundation for next-generation self-adaptive therapeutic platforms in regenerative medicine.