Temperature‐ and pH‐Responsive Near‐Infrared‐Activated Hydrogel With Synergistic Antibacterial Activity

ABSTRACT The escalating threat of multidrug‐resistant bacteria highlights the urgent need for innovative nonantibiotic strategies. Herein, we report a multifunctional smart hydrogel, P(NIPAM‐co‐MAA/OHA)@PDA, engineered for synergistic wound therapy. It was fabricated via one‐pot free‐radical copolymerization of N ‐isopropylacrylamide (NIPAM) and methacrylic acid (MAA), with simultaneous incorporation of oxidized hyaluronic acid (OHA) and polydopamine nanoparticles (PDA). The designed hydrogel exhibits dual temperature and pH responsiveness: the PNIPAM network enables thermally triggered bacterial sequestration under physiological temperature conditions (near body temperature), while the MAA component enhances interfacial interactions with bacterial surfaces in the acidic microenvironment of infected wounds. Notably, the as‐prepared hydrogel demonstrates excellent mechanical properties, including a tensile elongation up to 10 times its original length, superior self‐healing capability, and strong tissue adhesion performance. Upon near‐infrared (NIR) irradiation, the embedded PDA nanoparticles efficiently generate localized hyperthermia, which achieves direct and effective ablation of the sequestration pathogens. This unique integration of responsive bacterial sequestration and NIR‐triggered thermal ablation confers a potent synergistic antibacterial effect, with eradication rates exceeding 80% against both Escherichia coli and Staphylococcus aureus . Furthermore, the hydrogel shows excellent biocompatibility and can promote fibroblast proliferation in vitro, highlighting its great potential for clinical wound healing applications.