A ROS scavenging multifunctional hydrogel crosslinked with EGCG promotes the healing of pressure injuries via Nrf2 pathway

Pressure injuries (PIs) have emerged as a significant burden on individuals and society, lacking effective treatment due to the compromised wound microenvironment resulting from ischemia-reperfusion injury. The accumulation of excessive reactive oxygen species (ROS) is the core mechanism of delayed wound healing, which triggers a cascade of harmful events, including chronic inflammation, impaired angiogenesis, and abnormal ECM degradation. Epigallocatechin gallate (EGCG) is a natural antioxidant that has been reported to promote angiogenesis and suppress inflammation, but its application is limited by low bioavailability. Herein, we employed EGCG as a crosslinker to develop a multifunctional HA-PBA/EGCG hydrogel (abbreviated as HPE) to enhance EGCG bioavailability for PIs treatment. Specifically, HPE hydrogel was prepared by the formation of the boronic ester bonds through the reaction of EGCG and phenylboronic acid-modified hyaluronic acid, and evaluated for self-healing, injectability, antioxidant activity, biocompatibility, and pH- and ROS-responsiveness. In vitro, HPE hydrogel effectively improved cell migration and protected NIH3T3 and HUVECs from TBHP-induced oxidative damage. These effects collectively improved the PI microenvironment in vivo, activated the antioxidant Nrf2/HO-1/NQO1 pathway to reduce oxidative stress damage, promoted M2 macrophage polarization, suppressed inflammation, improved neovascularization, and enhanced collagen deposition and remodeling, accelerating tissue regeneration and wound closure. In summary, these findings highlight the pronounced therapeutic potential and effectiveness of this multifunctional hydrogel in overcoming the multifaceted challenges of chronic PI wounds.