Injectable reactive oxygen and nitrogen species-scavenging hydrogels for repairing traumatic brain injury

Clinical therapies for traumatic brain injury included pharmacological interventions and surgical procedures; however, the efficacy of these approaches remains unsatisfactory. Traumatic brain injury was commonly accompanied by excessive reactive oxygen species (ROS) and nitrogen species (RNS). The overexpressed ROS/RNS generally led to secondary brain injury. To address these issues, we synthesized the injectable poly (ethylene glycol) diacrylate (PEGDA)/cystamine/agmatine (PCA) hydrogels through Michael addition for repairing traumatic brain injury. Injectable PCA hydrogels could not only fill the brain trauma cavities, but also alleviate the secondary damage to the brain by reducing ROS and RNS. The disulfide bonds of cystamine and agmatine in the hydrogels could separately scavenge ROS and inhibit the activity of nitric oxide synthase. Consequently, injectable hydrogels were locally administrated to the injured brain. Therapeutically, PCA hydrogels significantly enhanced the motor functional recovery, improved the learning ability and memory retention, preserved the survival of neurons, and reduced the activation of glial cells and pro-inflammatory macrophages. The injectable hydrogels offered a potential therapeutic strategy for traumatic brain injury and other neurological diseases.