A bilayer polyurethane scaffold integrating degradation-dependent therapeutic release with directional exudate...

Diabetic wound management is compromised by infection, oxidative stress, and viscous exudates that dilute therapeutic agents. We report a spatially organized bilayer polyurethane scaffold designed to address these barriers. The scaffold integrates: (i) a hydrophilic layer with covalently bound L-arginine and ascorbic acid for degradation-dependent nitric oxide generation and ROS scavenging; (ii) a hydrophobic layer presenting REDV peptides for endothelial recruitment; and (iii) aligned microchannels with engineered wettability gradients enabling directional transport of viscous exudates (up to 90 mPa·s). This architectural segregation prevents therapeutic dilution while promoting regeneration. In diabetic infected wounds, the scaffold achieved 91.7% closure by day 12, significantly outperforming controls (43.8%) and commercial Tegaderm (56.7%). Treatment facilitated bacterial clearance, inflammatory resolution (reduced TNF-α/IL-1β, elevated IL-10), growth factor upregulation, and robust vessel maturation. These findings demonstrate that orchestrating degradation-dependent therapeutic release with directional fluid transport offers a potent translational strategy for chronic wound treatment.