Mechanistic Insights Into Plasma‐Activated Hydrogel: RONS Transport, Storage, and Bactericidal Synergy

ABSTRACT Microbial infections, particularly those caused by drug‐resistant microorganisms, pose major socioeconomic and global public health threats. Cold atmospheric pressure plasma can generate reactive oxygen and nitrogen species (RONS) with potent antimicrobial activity and minimal biosafety concerns. Plasma‐activated hydrogel (PAH) has attracted increasing interest due to its 3D network structure, which can extend the lifetime of RONS. This study investigates the mechanisms governing the loading, storage, and interactions of RONS in hydrogels. The loading of RONS in hydrogels can be divided into two phases: interfacial dissolution and penetration into the hydrogel matrix. A diffusion‐reaction model is established to describe the penetration process, demonstrating that RONS transport is governed by the coupling of diffusion and chemical reactions. Furthermore, vacuum freeze‐dried PAH enables effective incorporation of RONS into the polymer framework for storage, with liquid‐phase RONS being regenerated upon rehydration. Experimental results reveal that RONS can induce the release of NH 4 + from the AVC hydrogel, and the synergistic interaction between NH 4 + and RONS significantly enhances the bactericidal efficacy of PAH. These findings elucidate the fundamental mechanisms of RONS loading and storage in hydrogels and provide a mechanistic basis for the rational design of highly effective plasma‐activated antimicrobial materials.