A pH-Sensitive and ROS-Responsive Hydrogel Enhanced by Arginine-Derived Carbon Dots for the Diagnosis and Treatment of Infected Wounds.

Effective repair of infected wounds requires both precise elimination of bacteria in the host and accelerated healing, yet strategies that integrate real-time diagnosis with targeted therapy remain scarce. Here, we synthesize L-arginine-derived carbon quantum dots (Arg‑CQDs) and incorporate them into a poly(ethylene glycol) diacrylate/carboxymethyl chitosan (PEGDA/CMCS) double-network hydrogel via free-radical polymerization. The resulting Arg‑CQDs-enhanced hydrogel functions as a sensitive pH-responsive optical sensor. Density functional theory (DFT) calculations reveal that under acidic conditions, Arg‑CQDs possess a smaller HOMO-LUMO gap and a larger oscillator intensity, favoring intense radiative electronic transitions. Under alkaline conditions, a larger gap and a smaller oscillator intensity promote dominant non‑radiative transitions. Consequently, the ultraviolet (UV)-excited luminescence intensity of the composite hydrogel decreases as pH increases, enabling visual assessment of infection via smartphone-based RGB color channel analysis. Moreover, the hydrogel exhibits microenvironment-selective pro-oxidant and antioxidant behavior. In bacterial environments, the positively charged Arg‑CQDs disrupt the electron transport chain and elevate reactive oxygen species (ROS) levels, achieving potent bactericidal activity. In cellular environments, they scavenge excess ROS through the up-regulation of GGT5 and Aldo-Keto reductase, thereby activating JAK2-STAT3/IL‑10 signaling to promote macrophage anti-inflammatory responses. In a rat model of infected wounds, this hydrogel achieves re‑epithelialization and vascularized wound closure within 14 days, outperforming commercial Ag+ dressings. This "sense‑and‑act" smart hydrogel represents a promising platform for the simultaneous diagnosis and treatment of infected wounds. STATEMENT OF SIGNIFICANCE: This work reports an Arg-CQDs-enhanced PEGDA/CMCS composite hydrogel that functions as a pH-responsive optical sensor, enabling smartphone‑based visual assessment of infection. DFT calculations reveal that acidic conditions promote intense radiative electronic transitions, whereas alkaline conditions favor weak non-radiative transitions, accounting for the pH‑dependent luminescence. Furthermore, the hydrogel exhibits microenvironment‑selective behavior. In bacterial niches, it elevates ROS levels to achieve potent sterilization. In cellular environments, it scavenges excess ROS and up-regulates GGT5 and Aldo‑Keto reductase, thereby activating JAK2-STAT3/IL-10 signaling to orchestrate anti-inflammatory responses. In a rat model of infected wounds, this "sense‑and‑act" hydrogel accomplishes complete re-epithelialization and vascularized closure within 14 days, outperforming commercial Ag+ dressings. Collectively, these findings establish a promising platform for the simultaneous diagnosis and treatment of infected wounds.