Tri-layer structured intelligent hydrogel dressing for controlled-release antibacterial treatment of chronic diabetic wounds

Abstract

Chronic diabetic wounds are notoriously difficult to heal due to a hyperglycemic environment, persistent oxidative stress, and infection, leading to slow healing and frequent complications. In this study, we developed a tri-layer intelligent hydrogel dressing for diabetic wound care. The top layer contains silver nanoparticles (AgNPs) for rapid initial antibacterial action. The middle layer incorporates poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with mangiferin to achieve sustained drug release and promote angiogenesis. The bottom layer is a gelatin methacryloyl (GelMA) hydrogel scaffold that provides structural support. The composite materials' morphology and structure were characterized by scanning and transmission electron microscopy (SEM, TEM). We evaluated the properties of hydrogel contain mechanical properties, degradation and swelling behaviors, drug release profiles, antibacterial and antibiofilm effects, and cell-related biological properties. The results showed that the tri-layer hydrogel exhibited higher mechanical strength and greater degradation stability than a homogeneous GelMA hydrogel. The layered structure of hydrogel effectively delayed the release of mangiferin, resulting in a significantly lower cumulative release over 72 hours compared to a non-layered control. Antibacterial tests demonstrated that the tri-layer hydrogel produced the largest inhibition zones and the highest bacterial-killing rates against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and it markedly inhibited the formation of bacterial biofilms. In vitro, cell studies showed that the tri-layer hydrogel significantly downregulated the pro-inflammatory cytokines IL-6 and TNF-α, upregulated the anti-inflammatory cytokine IL-10, and substantially reduced intracellular reactive oxygen species (ROS) accumulation. In summary, the tri-layer intelligent hydrogel dressing, through its synergistic controlled-release and antibacterial mechanisms, offers an effective multi-factorial intervention strategy for the treatment of chronic diabetic wounds.