Smart bilayer hydrogels based on chitosan and its derivatives for wound repair and visual detection of blood glucose by triggering a cascade enzyme system

Impaired wound healing is one of the major consequences of diabetes, making the development of a more effective treatment for chronic diabetic wounds imperative. Herein, a bilayer hydrogel platform based on chitosan and its derivatives and conjugated with zeolitic imidazole framework-8 (ZIF-8) loaded with glucose oxidase (GOx) was designed, which was used to detect blood glucose content and promote wound healing. Specifically, encapsulation of GOx with ZIF-8 nanoparticles (GZ) were incorporated into the oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS) hydrogel to construct an inner hydrogel (GZ-OC hydrogel), while the outer hydrogel (CP hydrogel) composed of chitosan/polyvinyl alcohol (CS/PVA) contained 3,3′,5,5′-tetramethylbenzidine (TMB) and horseradish peroxidase (HRP). Leveraging differential swelling and pore sizes between layers, inner-generated H 2 O 2 activated the TMB-HRP system in the outer layer, enabling visual glucose quantification (1–20 mmol·L −1 ) within 20 min. Meanwhile, GZ and natural polysaccharides (CS and CMCS) enabled the bilayer hydrogel to have high antibacterial properties and good biocompatibility, and the bacterial infected wound of diabetic rats basically heals completely within 13 days. This dual-functional platform provided a rapid, safe strategy for personalized diabetic wound management through integrated glucose sensing and antimicrobial regeneration.