pH- and glucose-responsive antioxidant hydrogel promotes diabetic wound healing

Excessive oxidative stress and persistent inflammation are key factors contributing to the formation of diabetic chronic wounds. Delivering antioxidants through a microenvironment-responsive hydrogel system can effectively enhance wound healing and tissue regeneration. In this study, we developed a novel pH- and glucose-responsive hydrogel using Schiff base reaction and phenyl borate group for intelligent antioxidant release. Hyaluronic acid (HA) modified with phenylboronic acid (PBA) (HA-PBA) was oxidized to form OHA-PBA, which was then crosslinked with carboxymethyl chitosan (CMCS) and incorporated Proanthocyanidins (PA) to create an OHA-PBA/CMCS/PA (OPCP) hydrogel. The reversible nature of imine and borate groups enabled the responsive release of PA from OPCP hydrogels under acidic and high glucose conditions. The OPCP hydrogel exhibited excellent biocompatibility, suitable mechanical properties, and biodegradability. Both in vitro and in vivo results demonstrated that the OPCP hydrogel effectively reduced reactive oxygen species (ROS), suppressed inflammation, promoted vascularization, accelerated collagen deposition, and facilitated diabetic wound healing. This strategy offers novel insights into microenvironment-responsive scaffolds, highlighting the potential application of this responsive antioxidant hydrogel scaffold for chronic diabetic wound treatment.