Novel\nGlucose-Responsive Antioxidant Hybrid Hydrogel\nfor Enhanced Diabetic Wound Repair

Abstract

Antioxidant\nhydrogel has exhibited great potential for diabetic\nwound treatment. However, it is still a difficult challenge to realize\nreactive oxygen species (ROS) scavenging in an intelligent manner.\nHerein, we designed a novel glucose-responsive antioxidant hybrid\nhydrogel for enhanced diabetic wound repair. In this study, phenylboronic\nacid (PBA) with unique glucose-sensitivity was modified onto a hyaluronic\nacid (HA) chain by one-step synthesis, which was then incorporated\ninto a polyethylene glycol diacrylates (PEG-DA) hydrogel matrix to\nobtain a novel hybrid hydrogel (PEG-DA/HA-PBA). Then, myricetin (MY)\nmolecules with strong antioxidant activity were immobilized into the\nhybrid hydrogel by the formation of a dynamic borate bond between\nthe polyphenol group of MY and the phenylboronic acid group of HA-PBA.\nThe PEG-DA/HA-PBA/MY (PHM) hybrid hydrogel achieved glucose-triggered\nMY release, efficient ROS-scavenging (>80.0%), and also reshaped\nthe\nhostile oxidative wound microenvironment (reduced MDA activity and\nincreased SOD and GSH/GSSG levels). Furthermore, in vitro and in vivo\nresults indicated that the PHM hydrogel platform effectively ameliorated\nthe inflammatory response (decreased IL-6 and increased Il-10 expression),\naccelerated angiogenesis (increased VEGF and CD 31 expression), and\nincreased tissue remodeling within 20 days, which was better than\nthe nonresponsive PEG-DA/MY (PM) hydrogel platform in promoting diabetic\nwound healing. All results strongly suggested that this novel glucose-responsive\nantioxidant hybrid hydrogel platform has great potential in diabetic\nwound repair.