Injectable thermosensitive chitosan-based hydrogel containing ferulic acid for treating peripheral arterial disease

Peripheral arterial disease (PAD) affects more than 200 million people worldwide. Recent studies suggest that oxidative stress-related inflammation can lead to the initiation and progression of PAD. Ferulic acid (FA) is a natural phenolic compound and has been proven to have antioxidant and angiogenesis effects. In this study, thermosensitive chitosan–gelatin-based hydrogel was used as a delivery vehicle of FA. The effects of hydrogel encapsulating FA (FA-gel) have been demonstrated in vitro and in vivo. The results revealed that the developed hydrogel with porous structure could provide a sustained release of FA. Post-treatment of FA-gel effectively decreased the oxidative stress-induced damage in human umbilical vein endothelial cells via decreasing endogenous reactive oxygen species production, inflammation-related gene expression and apoptosis level. In the mouse hindlimb ischemia model, the results revealed that FA-gel could improve blood flow, muscle regeneration and decreases inflammation in veins. These results suggested that FA-gel may have a therapeutic potential in PAD.