Curcumin-loaded multifunctional hydrogel drives spinal cord neural regeneration through immune microenvironment remodeling

Spinal cord injury (SCI) is a severe central nervous system disorder that leads to long-term neurological dysfunction. Currently, there are no effective clinical treatments, making it imperative to develop novel therapeutic strategies that can simultaneously regulate immune responses and promote neural regeneration. Here, we designed and prepared an injectable self-healing multifunctional hydrogel composed of gelatin, quaternized chitosan, polydopamine, and curcumin. This hydrogel integrates immune microenvironment remodeling, spinal cord-matched mechanical properties, excellent biocompatibility, and sustained curcumin release for up to 14 days, effectively covering the critical acute-to-subacute phases of SCI repair. In vitro studies demonstrated that the hydrogel effectively scavenged reactive oxygen species (ROS) and induced macrophage polarization towards the anti-inflammatory M2 phenotype. In the rat model of SCI, treatment markedly alleviated oxidative stress and neuroinflammation during the acute phase, inhibited glial scar formation, promoted axonal and myelin regeneration, and ultimately improved motor function recovery. Collectively, this study presents a promising platform for SCI treatment and other central nervous system disorders by remodeling the immune microenvironment.