Engineered Bilayer Hydrogel with Spatiotemporal Drug and Oxygen Delivery for Diabetic Wound Microenvironment Reprogramming

The study introduces an engineered bilayer hydrogel designed for diabetic wound healing by addressing persistent inflammation, hypoxia, and infection susceptibility. The hydrogel, named Ca@Q-E@SGH, utilizes a spatiotemporal drug and oxygen delivery system. It features a core component of calcium peroxide encapsulated by phenylboronic acid-modified quaternary ammonium chitosan, with EGCG linked via boronate esters. This setup allows for ROS/glucose-responsive EGCG release, reprogramming macrophages from the M1 to M2 phenotype to reduce early inflammation. As the matrix degrades, sustained oxygen release supports vascularization. The bilayer structure provides protective functions, with a lower layer encapsulating nanoparticles and an upper hydrophilic anti-fouling coating. This platform achieves a 99.1% wound closure rate by day 14, offering a comprehensive strategy for diabetic wound management through smart anti-inflammatory action, prolonged oxygen supply, and anti-fouling capacity.