Ferrostatin-1 loaded Gelatin methacrylate scaffold promotes recovery from spinal cord injury via inhibiting apoptosis and ferroptosis

Spinal cord injury (SCI) is a traumatic disease that seriously damages the central nervous system, which will bring a heavy burden to patients physically, mentally and economically. Ferroptosis is a newly discovered mode of cell death in recent years. It has been found that ferroptosis is related to a variety of diseases (stroke, traumatic brain injury, neurodegenerative diseases, etc.), and plays a major role in secondary injury after spinal cord injury. Ferrostatin-1 (Fer-1) is a potent inhibitor of ferroptosis that has been shown to improve functional recovery after SCI by alleviating white matter damage. Gelatin methacrylate (GelMA) hydrogels can carry drugs/nanomaterials into the body and have a slow release and physical support. However, the specific role of the GelMA hydrogel-based Fer1 slow-release system in neuronal iron death after SCI remains unknown. In this study, we demonstrate for the first time that the Fer@GelMA slow-release system inhibits apoptosis and promotes neuronal survival by inhibiting ferroptosis, ultimately rescuing damaged tissue and promoting recovery of SCI motor function. This discovery may provide a new treatment strategy for SCI.