Glucose‐Responsive Injectable Hydrogel for Enhanced Sonodynamic‐Antibacterial Cascade Therapy of Diabetic Abscess

Abstract Diabetic subcutaneous abscesses present significant therapeutic challenges due to persistent bacterial infection, hypoxia, hyperglycemia, and biofilm formation. Herein, an injectable, microenvironment‐responsive hydrogel (CaO 2 /GOx/Ti 3 C 2 @Alg) is engineered capable of dynamically modulating the hyperglycemic and hypoxic conditions of diabetic abscesses while enabling targeted eradication of methicillin‐resistant Staphylococcus aureus (MRSA) via a cascaded therapeutic strategy. In the acidic abscess, CaO 2 nanoparticles decomposed to release Ca 2+ and oxygen, which can trigger the in situ formation of hydrogel via ionic cross‐linking with sodium alginate (Alg) and relieve the hypoxic microenvironment, respectively. Glucose oxidase (GOx), an efficient biocatalyst, selectively depleted excess glucose to generate H 2 O 2 , which subsequently triggered the oxidative transformation of Ti 3 C 2 MXene into TiO 2 . Under ultrasound (US), the in situ‐generated TiO 2 exhibited exceptional sonodynamic activity, producing abundant singlet oxygen ( 1 O 2 ) for biofilm eradication and potent MRSA elimination without systemic toxicity. These findings demonstrate that this multifunctional injectable hydrogel, capable of dynamic microenvironment regulation and precise MRSA eradication through cascaded therapy, represents a promising strategy for diabetic abscess treatment.