Schiff Base-Based pH-Responsive Self-Healing Hydrogel for Intelligent Delivery of ZIF-8-Encapsulated Curcumin in Synergistic Osteomyelitis Therapy

Osteomyelitis is a devastating bone disease caused by bacterial infection, the treatment of which remains challenging due to bacterial biofilm formation and impaired bone regeneration. The development of an integrated therapeutic platform capable of locally filling bone defects, enabling controlled drug release and modulating the infectious microenvironment is of crucial importance. This study constructed an injectable self-healing hydrogel based on Schiff base bonds for pH-triggered delivery of ZIF-8-loaded curcumin, aiming to achieve synergistic therapy for osteomyelitis. Curcumin-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized via a one-pot method and embedded into an oxidized starch–gelatin hydrogel network formed by dynamic Schiff base crosslinking, yielding the composite hydrogel. Systematic characterization revealed that the ZIF-8@Cur nanoparticles exhibited a well-defined rhombic dodecahedral structure, high crystallinity and a curcumin encapsulation efficiency of 85%. The composite hydrogel demonstrated excellent injectability, rapid self-healing behavior and remarkable pH-responsive drug release: under the acidic condition mimicking an infectious microenvironment (pH 5.5), the cumulative release over 72[Formula: see text]h reached 85%, significantly higher than the 25% observed at physiological pH 7.4. In vitro antibacterial assays confirmed its potent broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria ([Formula: see text]98% inhibition). More importantly, the system effectively promoted macrophage polarization from pro-inflammatory M1 to anti-inflammatory and reparative M2 phenotypes while exhibiting good biocompatibility. This study successfully developed an intelligent responsive injectable hydrogel delivery system integrating efficient antibacterial, anti-inflammatory and immunomodulatory functions, offering a promising strategy for the comprehensive local treatment of osteomyelitis.