Multicross-Linked Hydrogels Encapsulating Carbon Nanoparticles and Enzyme-Carrying Microspheres for Antibacterial, Antioxidant, and Soft Tissue Remodeling Applications.

Diabetic chronic wounds pose significant clinical challenges due to hyperglycemia-induced oxidative stress, impaired angiogenesis, and bacterial infections. To address these issues, we developed an injectable multifunctional hydrogel composed of thiolated polylysine, chitosan, oxidized dextran, and antibacterial carbon nanoparticles (CNPs), integrated with glucose oxidase (GO x )-loaded microspheres (GSpheres). The hydrogel's dynamic network, formed through disulfide and Schiff base cross-linking, exhibits self-healing properties and glucose-responsive drug release. The embedded CNPs provide broad-spectrum antibacterial activity, while GO x effectively reduces wound-site glucose levels, mitigating glycation damage. In vitro studies confirmed the hydrogel's biocompatibility, hemocompatibility, and potent antibacterial effects against common pathogens. In vivo experiments demonstrated accelerated diabetic wound healing, with enhanced collagen deposition, angiogenesis, and reduced inflammation. This dual-functional system combines glucose regulation and infection control within a bioactive hydrogel matrix, offering a promising strategy for comprehensive diabetic wound management.