ROS‐Scavenging Hydrogels Synergize with Neural Stem Cells to Enhance Spinal Cord Injury Repair via Regulating Microenvironment and Facilitating Nerve Regeneration

Abstract Although stem cell‐based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)‐abundant and hyper‐inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO 2 @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS‐scavenging hydrogel (CeNP‐Gel). CeNP‐Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP‐Gel, microglial polarization to anti‐inflammatory M2 subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3‐kinase/protein kinase B pathway activation. Additionally, the injectable ROS‐scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank‐gel group, the survival rate of NSCs in CeNP‐Gel group is about 3.5 times higher, and the neural differentiation efficiency is about 2.1 times higher. Therefore, the NSCs‐laden ROS‐scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment.