Responsive dual-layer hydrogel microneedles accelerate diabetic wound healing via antibacterial and enzyme cascade regulation.

Chronic diabetic wounds do not heal and are often accompanied by infections and poor angiogenesis. We have made a two-layered PVA/CS composite hydrogel MN-CL patch, which has antibacterial, immunoregulatory, and pro-healing properties. The needle tips were loaded with the antimicrobial peptide LL-37 to achieve immediate bactericidal action when the needle penetrates the bacterial membrane, and the hydrogel base contained a GOx/CAT cascade system that could respond to hyperglycemic and acidic microenvironments. This system regulates the local glucose and ROS levels, promoting the transition of the wound from the inflammatory phase to the proliferative phase. In vitro experiments showed that the MN-CL patch had a strong antibacterial effect on bacteria, it could promote macrophages to change from M1 type to M2 type, and it could also promote the proliferation, migration, and angiogenesis of endothelial cells. Transcriptome analysis showed that the effects were mainly caused by the inhibition of inflammatory pathways such as IL-1 and NF-κB signaling and the activation of tissue repair-related pathways. In a diabetic rat infection model, the MN-CL patch greatly improved the rate of wound healing, angiogenesis, and collagen accumulation, indicating that this method may have potential for clinical application in treating chronic wounds.