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Oxidative stress caused by the overexpression of reactive oxygen species (ROS) plays an important role in the pathogenesis of traumatic brain injury (TBI). Accumulation of ROS can lead to cell death, neurodegeneration, and neurological deficit. Therefore, the design and application of functional materials with ROS scavenging ability is of great significance for neural repair. Herein, an injectable and antioxidant hydrogel was developed for TBI treatment based on the Schiff base reaction of gallic acid-conjugated gelatin (GGA) and oxidized dextran (Odex). The resulting GGA/Odex hydrogel could effectively scavenge DPPH and ABTS radicals, as well as protect cells from the oxidative damage in vitro. Moreover, GGA/Odex hydrogel possessed well biocompatible features. In a moderate TBI mouse model, in situ implantation of GGA 6 Odex hydrogel efficiently facilitated neurogenesis and promoted the motor, learning and memory abilities. Also, this composite hydrogel suppressed oxidative stress and inflammation via the activation of Nrf2/HO-1 pathway and the regulating of inflammatory factors secretion and macrophage/microglia polarization. Therefore, this injectable and ROS-scavenging GGA 6 Odex hydrogel is a promising biomaterial for tissue regenerative medicine, including TBI and other tissue repair relevant to raised ROS circumstance. [Display omitted] [ABSTRACT FROM AUTHOR]