Chitosan-Citric Acid Hydrogels Loaded with Catalpol: A Novel Therapeutic Strategy for Spinal Cord Injury

Background Spinal cord injury (SCI), which often results from traumatic incidents, leads to neural damage and impaired sensory and motor functions and may pose a serious threat to life. Secondary injury mechanisms caused by persistent inflammation disrupt the local microenvironment, causing neuronal cell death and hindering neural regeneration. This study used a chitosan-citric acid (CS-CA) hydrogel as a carrier for Catalpol (CAT-CS-CA), which was directly applied to the injury site to promote SCI repair. Methods CAT-CS-CA and CS-CA hydrogels were characterized and implanted into rat SCI models. 24 male Sprague-Dawley rats (230–250 g) were randomly assigned to four groups ( n = 6 per group) using a randomization principle: sham operation group (laminectomy only), SCI group, CS-CA hydrogel group, and CAT-CS-CA hydrogel group. Neuronal nuclei (NeuN), β III-tubulin (Tuj1), glial fibrillary acidic protein (GFAP), macrophage polarization (M1/M2 markers), and hindlimb function (BBB score) were assessed. Results The CAT-CS-CA hydrogel retains CS-CA hydrogel's advantages and gains enhanced neuroprotective and anti-inflammatory abilities. The implantation of CAT-CS-CA into injured rat spinal cords enhanced neuronal survival, stimulated axonal regeneration, and significantly suppressed glial proliferation at the injury site. In addition, it promoted macrophage polarization to the M2 phenotype and substantially enhanced hindlimb motor function in rats with SCI. Conclusion CAT-CS-CA hydrogel promotes neuronal survival, suppresses glial scarring, and improves motor function, offering a promising strategy for SCI repair.