Dynamic chemical bond-driven sustained release of GDN-PLGA microspheres in injectable composite hydrogels for enhanced wound healing

Abstract Traditional passive wound dressings struggle to meet the demands of effective wound management. This study developed an intelligent hydrogel composite wound dressing system with microenvironment-responsive characteristics, achieving controlled drug release by constructing a dynamic dual-network structure. Gastrodin-Poly (lactic-co-glycolic acid) (GDN-PLGA) drug-loaded microspheres, with a particle size of 20–80 μm and an encapsulation efficiency of 44.3 ± 2%, are co-loaded into the system, forming an injectable drug-loaded hydrogel (GOA-GDN-PLGA). The results demonstrated that the GOA-GDN-PLGA dual-network injectable hydrogel significantly promotes wound healing. In a rat full-thickness skin defect model, the treatment group achieved a healing rate of 85.4 ± 4% after 14 d, considerably better than the commercial dressing group (51 ± 2%, p <0.01). Histological analysis showed more organized collagen deposition and increased vascular density. These results indicate that the GOA-GDN-PLGA injectable drug-loaded hydrogel facilitates rapid hemostasis and enables controlled drug release, effectively addressing the challenge of multiple administrations of soluble drugs in traditional wound management.