Injectable and Reactive Oxygen Species-Scavenging Gelatin Hydrogel for Promoting Traumatic Brain Injury Treatment

Oxidative stress caused by the overexpression of reactive oxygen species (ROS) plays an important role in the pathogenesis of traumatic brain injury (TBI). The accumulation of ROS leads to a harsh brain microenvironment, which result in cell death, neurodegeneration, and neurological deficit. Therefore, the design of materials with ROS scavenging ability is of great significance. Herein, an excellent injectable and antioxidant hydrogel crosslinked by gallic acid-conjugated gelatin (GGA) and oxidized dextran (Odex) based on the Schiff base reaction was developed for TBI treatment. The GGA/Odex hydrogel could effectively scavenge DPPH radicals and hydroxyl radicals, as well as protect cells from the damage of oxidative stress in vitro . Moreover, GGA/Odex hydrogel possessed well biocompatible and antibacterial activity against escherichia coli (E. coli) and staphylococcus aureus (S. aureus). In a moderate TBI mouse model, in situ implanted GGA/Odex hydrogel efficiently facilitated nerve regeneration and promoted the recovery of motor, learning and memory functions in vivo. It is mainly because the inhibition of oxidative stress via the Nrf2/HO-1 pathway, and the reduction of inflammatory level by regulating the inflammatory factors secretion and macrophage/microglia polarization. Therefore, this injectable and ROS-scavenging GGA/Odex hydrogel is expected as a promising biomaterial for tissue regeneration applications, including TBI treatment and other tissues repair related to ROS overexpression. Funding Information: This work was financially supported by the National Natural Science Foundation of China (U1804198), the Key R&D and Promotion Projects in Henan Province (202102310211) from Minghao Yao, Zhongyuan Thousand Talents Project (204200510013) and the Discipline Innovation and Wisdom Introduction Plan of Higher Education in Henan Province (CXJD2021002) from Fangxia Guan. We also thank the facility support of the Center for Modern Analysis and Gene Sequencing, Zhengzhou University. Declaration of Interests: The authors declare no competing financial interest. Ethics Approval Statement: All animal procedures in this study were approved by the Animal Ethics Committee of Zhengzhou University and performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Zhengzhou University.