A Constant Filgotinib Delivery Adhesive Platform Based on Polyethylene Glycol (PEG) Hydrogel for Accelerating Wound...

Skin wound healing is often hindered by disrupted mitochondrial homeostasis and imbalanced macrophage glucose metabolism, posing a critical challenge to improve patient outcomes. Developing new wound healing dressings capable of effectively regulating macrophage immune-metabolic functions remains a pressing issue. Herein, a highly adhesive polyethylene glycol (PEG) hydrogel loaded with the Janus kinase 1 (JAK1) inhibitor Filgotinib (Fil@GEL) is prepared to modulate macrophage metabolic reprogramming and restore normal mitochondrial function. Fil@GEL exhibits superior shear adhesion strength compared to commercially available tissue binder products, providing adequate adhesion for skin wound closure. Additionally, Fil@GEL exhibits the capacity to inhibit M1-type macrophage polarization by suppressing the JAK-STAT signaling pathway, and induces a metabolic shift in macrophages from aerobic glycolysis to oxidative phosphorylation, which results in decreased lactate production, reduced reactive oxygen species (ROS) levels, and the restoration of mitochondrial homeostasis. The Fil@GEL hydrogel significantly accelerates skin wound healing compared to the control group, reduces intra-wound inflammation, and promotes collagen regeneration. In summary, this highly adhesive hydrogel demonstrates exceptional performance as a drug carrier, exerting immunometabolic modulation through firm wound adhesion and sustained filgotinib release, underscoring its substantial potential as an effective wound dressing.