3D-bioprinted skin-mimicking bilayer hydrogel dressing with compartmentalized antibacterial and pro-healing functions for diabetic wounds

Diabetic wound healing remains a significant clinical challenge due to persistent infection and impaired tissue regeneration. This study presents a biomimetic, 3D-bioprinted bilayer hydrogel dressing with spatially compartmentalized functions to address these divergent requirements. The upper layer comprises chitosan hydrogel embedded with silver nanoparticles to provide rapid, broad-spectrum antibacterial activity against surface pathogens, and the lower layer consists of methacrylated silk fibroin (SilMA) hydrogel co-encapsulating epidermal stem cell-derived exosomes and metformin to create a pro-regenerative microenvironment in deeper wound strata. Comprehensive in vitro characterization confirmed distinct physicochemical properties between the antibacterial upper layer and the porous, pro-healing lower layer. The upper layer exhibited synergistic bactericidal effects against S. aureus and E. coli, while the lower layer promoted M2 macrophage polarization, endothelial cell migration, and angiogenesis-related gene expression. In a diabetic mouse model of infected full-thickness wounds, compared to monolayer controls, the bilayer dressing significantly accelerated wound closure by increasing granulation tissue formation and neovascularization, while reducing bacterial burden. This compartmentalized design effectively integrates the complementary demands of infection control and tissue regeneration, offering a promising strategy for managing chronic diabetic ulcers.