Hydrogen‐bond‐mediated retention of a phenolic SNAP analogue in polyvinyl alcohol/PEG hydrogels for sustained nitric oxide release and antibacterial activity

Nitric oxide (NO)‐releasing materials have attracted considerable interest for their potential in diverse biomedical applications. However, a persistent challenge is the leaching of NO donors from these materials, which leads to significantly reduced NO release durations and undesirable burst release effects. Herein, we demonstrate a novel hydrogen‐bonding strategy to address NO donor leaching and the burst release of NO. A nitrosothiol‐based NO hydrogel was developed by incorporating a SNAP analog bearing a 4‐hydroxyphenethyl sidechain into polyvinyl alcohol (PVA)/PEG hydrogels. The hydrogel containing the structurally modified SNAP analog exhibited an elongation of over 300% and sustained NO release under physiological conditions. Hydrogen‐bonding interactions contributed to the enhanced retention of the SNAP analog within the hydrogel network, extending donor retention to 144 h compared with the hydrogel containing unmodified SNAP (10 h). These NO‐releasing hydrogels exhibited potent antibacterial activity against both S . aureus and E . coli , with bacterial reduction exceeding 99%, and caused pronounced disruption of surface‐associated bacterial structures. This novel hydrogen‐bonded NO donor–hydrogel system offers a promising strategy for durable and controlled NO release, with potential applications in wound dressings, tissue scaffolds, and flexible sensors.