A Constant Filgotinib Delivery Adhesive Platform Based on Polyethylene Glycol (PEG) Hydrogel for Accelerating Wound Healing via Restoring Macrophage Mitochondrial Homeostasis

Abstract

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.