Issue

Vol. 18 (2026)

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

https://doi.org/10.1007/s40820-026-02237-1
Pengfei Wen
Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, People’s Republic of China
Pan Luo
Department of Plastic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020, People’s Republic of China
Fuqiang Gao
Center for Hip Preservation, Osteonecrosis and Developmental Dysplasia of the Hip, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of China
Mingyi Yang
Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, People’s Republic of China
Junyou Li
School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, South Korea
Zhi Yang
Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, People’s Republic of China

Corresponding Author: Zhi Yang

yangzhi@xiyi.edu.cn

Nano-Micro Letters, Vol. 18 (2026), Article Number: 385

Abstract

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.


Highlights:
1 Pd-Ni5P4/dual-channel electrocatalytic flexible system (DCEFS) employs a bifunctional catalyst, dual-channel electrodes, and microneedle array to achieve continuous, decoupled-free coupling of nitric oxide sensing and hydrogen treatment.
2 Pd-Ni5P4/DCEFS pioneers a single-cycle “sense-hydrogen treatment-sense” strategy for closed-loop inflammation resolution, delivering efficient reactive nitrogen species/reactive oxygen species clearance with real-time nitric oxide-based feedback for precise therapeutic control.
3 Pd-Ni5P4/DCEFS innovatively establishes a closed-loop ‘sense-hydrogen treatment-sense’ paradigm guided by lesion-specific NO levels, enabling on-demand hydrogen intervention to potently resolve inflammation, robustly drive tissue regeneration, and markedly accelerate diabetic wound healing with excellent biocompatibility.

Keywords

NO sensing Anti-inflammatory hydrogen treatment Closed-loop therapy Decoupled-free coupling Diabetic wound healing
Wen, Pengfei, Pan Luo, Fuqiang Gao, Mingyi Yang, Junyou Li, and Zhi Yang. 2026. “Closed-Loop Synergistic Nitric Oxide/Hydrogen Delivery With Feedback Control for Diabetic Wound Healing”. Nano-Micro Letters 18 (May):385. https://doi.org/10.1007/s40820-026-02237-1.
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