Photo-crosslinkable quaternized chitosan-based hydrogel for immunomodulation and functional recovery in spinal cord injury

Spinal cord injury (SCI) causes severe neurological deficits and remains difficult to treat with current strategies such as surgical decompression or corticosteroids, which offer limited benefits. Hydrogels represent a promising alternative because they provide structural support and serve as therapeutic carriers. Quaternized chitosan (QCS), a derivative of chitosan, shows improved solubility and anti-inflammatory properties but lacks crosslinking ability and degrades rapidly, restricting its application in SCI. To overcome these limitations, we introduced methacrylate groups into QCS (QCS-MA), enabling photo-crosslinking, faster gelation, and enhanced mechanical stability while preserving bioactivity. QCS-MA was blended with type I collagen to form an interpenetrating hydrogel (QCS-MA/COL) through hydrogen bonding, then loaded with progranulin (PGRN), a multifunctional growth factor known to promote neuronal survival and modulate immune responses. The resulting PGRN@QCS-MA/COL hydrogel displayed favorable mechanical properties, injectability, and biocompatibility, while inducing macrophage polarization toward a reparative M2 phenotype. In a mouse SCI model, it significantly improved motor recovery, reduced lesion cavity formation, attenuated chronic inflammation, and enhanced axonal and neural regeneration. These findings highlight the potential of QCS-MA as a tunable immunomodulatory delivery platform, synergizing with PGRN and collagen to provide a biomimetic strategy for neural repair.