Construction of a Thermoresponsive and Controllably Shrinkable Dual-Network Hydrogel Incorporating Copper-Doped Prussian Blue Nanozymes with In Vitro Antibacterial and Antioxidant Activities

Abstract Infection-associated wounds are typically characterized by elevated bacterial burden, oxidative stress imbalance, and highly heterogeneous microenvironments, whereas conventional hydrogels remain limited in achieving rapid in situ gelation, stimuli-responsive deformation, and on-demand release of functional components. To address these challenges, this work presents a thermoresponsive, controllably shrinkable, copper-doped Prussian blue nanozyme-based dual-network hydrogel (SGCP@CuPB). In situ polymerized PNIPAM constitutes a thermosensitive covalent first network that enables rapid initial gelation and heat-triggered shrinkage, while an SA/GDL/CaCO3-based ionically crosslinked second network is subsequently established to progressively consolidate the network architecture and reinforce mechanical strength. Embedded CuPB nanozymes confer near-infrared (NIR) photothermal conversion, multi-enzyme-mimicking activity, and reactive oxygen species (ROS)-regulating capability. SGCP@CuPB-1 gels within 2 min, and its gelation time can be tuned from 2 to 10 min by adjusting the APS/TEMED dosage. Upon 808 nm NIR irradiation, SGCP@CuPB-1 undergoes controllable shrinkage, thereby promoting the outward migration and responsive release of CuPB. Cu doping modulates the local electronic environment of PB, enhancing its NIR absorption, photothermal conversion, and catalytic activity, which enables SGCP@CuPB to achieve a photothermal conversion efficiency of 37.0% while exhibiting SOD-like, CAT-like, and POD-like multi-enzyme-mimicking activities along with enhanced ROS-scavenging capacity. Upon NIR irradiation, SGCP@CuPB achieves antibacterial rates of 96.3%, 92.5%, and 86.8% against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively. Collectively, SGCP@CuPB integrates sequential dual-network construction, thermoresponsive and NIR-enhanced shrinkage, NIR-enhanced CuPB release, ROS regulation, and in vitro antibacterial function, providing a responsive hydrogel design for infection-associated wound microenvironments.