A dual-component particulate dressing for simultaneous microenvironment modulation and tissue regeneration in infected diabetic wounds

The treatment of chronic diabetic wounds faces considerable challenges owing to complex environments in the wound bed, such as chronic inflammation, excessive reactive oxygen species (ROS), impaired extracellular matrix (ECM) and bacterial infection. Current strategies, including bandages, hydrogel dressings and medical devices, that focus solely on a few pathological features have limited success. Herein, a fast self-gelling polyacrylic acid (PAA) derivative/madecassoside (MA) particulate dressing with anti-inflammatory, antioxidative, collagen deposition-promoting and intrinsic antibacterial properties is developed to simultaneously regulate the wound microenvironment and promote tissue regeneration in infected diabetic wounds. The incorporation of N-[Tris(hydroxymethyl)methyl]acrylamides (THMA), a small molecule compound that has three hydroxy groups clustered together, into the PAA backbone confers the copolymer with self-gelation, robust wet tissue adhesion and a strong capacity to load MA via multiple hydrogen bonding. The developed dual-component particulate dressing effectively regulated macrophage polarization towards the anti-inflammatory phenotype, and displayed potent antibacterial activity against both Gram-positive <i>S. aureus</i> (99.2 %) and Gram-negative <i>E. coli</i> (90.8 %) at a dose of 8 mg mL^-1. Further, the dressing obviously accelerated the healing of full-thickness skin wounds compared with commercial fibrin glue in a <i>S. aureus</i>-infected diabetic mouse model. This multifunctional PAA-based wound dressing is potentially valuable for clinical applications towards diabetic foot ulcers, pressure ulcers and other conditions of acute or chronic wounds.