Cascaded catalytic amplification by a phenylboronate ester-based double-network hydrogel for synergistic eradication of multidrug-resistant bacteria and diabetic wound healing

Diabetic chronic wounds are plagued by hyperglycemic microenvironments, multidrug-resistant (MDR) bacterial colonization and biofilm formation. In this study, glucose oxidase (GOx)/ 60 nm CuS nanoparticles were incorporated into an adhesive phenylboronic acid-modified, hyaluronic acid/quaternized chitosan (HA-PBA/QCS) dynamic boronate hydrogel (GS 128 @HPQ). GOx catalyzes glucose to generate H 2 O 2 , and CuS, under 808 nm near-infrared irradiation, acts as a Fenton-like catalyst to generate ·OH and also displays photothermal activity that elevates local temperatures to 45–65 °C in vitro, resulting in a synergistic antibacterial effect. The hydrogel has a porous structure with a pore size of approximately 50 μm, exhibits reactive oxygen species (ROS)-responsive drug release, possesses excellent mechanical properties including favorable rheological behavior, a tensile strength of 140 kPa, and self-healing capacity, and demonstrates adhesion properties ideal for wound dressing applications. In vitro, HA-PBA/QCS showed >98% MDR bacterial and more than 85% biofilm clearance. In diabetic mouse infected wound models, the wound area was <5% on Day21, with a > 70% downregulation of inflammation biomarkers IL-6/TNF-α and upregulation of VEGF/CD31, enables rapid re-epithelialization and collagen maturation, while the hydrogel has a hemolysis rate of less than 5%. This hydrogel provides a safe, efficient, and multifunctional platform for treating chronically infected diabetic wounds.