Injectable ROS homeostasis protective hydrogel inhibiting microglial ferroptosis through the Nrf2/Slc7a11/Gpx4 to alleviate neuropathic pain and promote spinal cord injury repair.

ABSTRACT: Spinal cord injury (SCI) induced neuropathic pain (NP) remains a major clinical challenge due to persistent neuroinflammation and oxidative stress. We developed an injectable methacrylated and thiolated gelatin hydrogel loaded with quercetin (MSQ) to synergistically scavenge reactive oxygen species (ROS) and inhibit microglial ferroptosis for NP alleviation and neural repair. The MSQ hydrogel exhibited rapid photocrosslinking, sustained quercetin release, and robust ROS scavenging via thiol groups and quercetin, maintaining intracellular redox homeostasis. MSQ attenuated LPS-induced ferroptosis in BV2 microglia by upregulating Nrf2 expression, promoting its nuclear translocation, and activating the Slc7a11/Gpx4 pathway, thereby reducing lipid peroxidation and inflammatory cytokine release.

SUBMITTER: Li L 

PROVIDER: S-EPMC12359189 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature