An In Situ Assembled Trapping Gel Repairs Spinal Cord Injury by Capturing Glutamate and Free Calcium Ions

Abstract Spinal cord injury (SCI) can lead to devastating autonomic dysfunction. One of the most challenging issues for functional repair in SCI is the secondary damage caused by the increased release of glutamate and free Ca²⁺ from injured cells. Here, an in situ assembled trapping gel (PF‐SA‐GAD) is developed to sweep glutamate and Ca²⁺, promoting SCI repair. The hydrogel solution is a mixture of recombinant glutamate decarboxylase 67 (rGAD67) protein, sodium alginate (SA), and pluronic F‐127 (PF‐127). After intrathecal administration, temperature‐sensitive PF‐127 promoted in situ gelation. Glutamate (Glu) is captured and decarboxylated by rGAD67 into γ‐aminobutyric acid (GABA). SA reacted with the free Ca²⁺ to generate gellable calcium alginate. Thereby, this in situ trapping gel retarded secondary neuron injury caused by Glu and free Ca²⁺ during SCI. In rat models of SCI, PF‐SA‐GAD reduces the lesion volume and inflammatory response after SCI, restores the motor function of rats with SCI. Together, the in situ assembled trapping gel is a long‐term effective and minimally invasive sweeper for the direct elimination of glutamate and Ca²⁺ from injury lesions and can be a novel strategy for SCI repair by preventing secondary injury.