Electroactive Hydrogel Enabling Feedback‑Responsive Monitoring and Regulation of Inflammation for Chronic Wound Therapy

Abstract

Chronic wounds remain a major clinical challenge due to persistent inflammation, excessive oxidative stress, and impaired tissue regeneration. Herein, we developed a multifunctional hydrogel dressing (GX/ML) by integrating a reactive oxygen species (ROS)‐responsive dynamic borate ester cross‐linking network with electrocatalytic MXene nanosheets and anti‐inflammatory luteolin. The hydrogel enables real‐time monitoring of wound inflammation through electrochemical sensing of H2O2 levels, while on‐demand drug release is triggered by either high ROS or near‐infrared irradiation. In vitro and in vivo results demonstrated exceptional ROS‐scavenging capability, efficient antibacterial activity (>96% against S. aureus and E. coli), and promotion of macrophage polarization toward the pro‐healing M2 phenotype. In a diabetic mouse wound model, the GX/ML hydrogel accelerated wound closure (98.1% healing rate by day 19), enhanced angiogenesis, collagen deposition, and re‐epithelialization, and modulated immune responses via cytokine signaling pathways (e.g., NF‐κB and NOD‐like receptor pathways). Transcriptomic analysis confirmed regulation of genes related to immune inflammation and tissue remodeling. This work provides a synergistic strategy through a smart hydrogel platform that integrates real‐time inflammatory monitoring with condition‐triggered drug release, offering a feedback‐responsive approach for chronic wound management.