Natural small molecule-induced polymer hydrogels with inherent antioxidative ability and conductivity for neurogenesis and functional recovery after spinal cord injury

Spinal cord injury (SCI) is a permanent disabling condition of the central nervous system. The secondary oxidative stress and the interruption of nerve electrical signal conduction are the main obstacles in the repair of SCI. Benefiting from the inherent capability for reactive oxygen species (ROS) scavenging by α-lipoic acid (LA) and the therapeutic effect by LiCl as well as conductivity in aqueous solution, we develop advanced hydrogels (poly(lipoic acid-co-sodium lipoate) (PLL) hydrogels) through one-pot ring-opening polymerization of LA in the presence of NaHCO3 for the efficient treatment of SCI. The hydrogels show facile injectability, adequate adhesiveness with tissues, and promising self-healability and can scavenge ROS in vitro and in vivo with high performance. Moreover, in the rat SCI model, PLL hydrogels facilitate electrophysiological signal transduction of nerve fibers at the injury site, regulate oxidative stress and inflammation in situ, and inhibit glial scar formation to promote neural stem cell migration and differentiation into neurons, all of which contribute to fast functional recovery after SCI. As the raw materials are safe and the fabrication process is easily scalable, the developed PLL hydrogels represent a cost-effective strategy for the regeneration of different injured tissues in clinical settings.