Injectable Zn ²⁺ ‐Alginate Hydrogel Delivering NT3 for Anti‐Inflammatory and Neuroregenerative Therapy in Spinal Cord Injury

Utilizing hydrogels to remodel the adaptive microenvironment provides an effective strategy for mitigating chronic inflammation in spinal cord injury (SCI) repair. However, the persistent detrimental impact of inflammation on SCI remains a critical issue requiring urgent resolution. This study developed an in situ cross‐linked alginate hydrogel stabilized by Zn ²⁺ coordination, functionalized with His‐tagged NT3 to enable anti‐inflammatory modulation and neural regeneration following SCI. The hydrogel consists of sodium alginate, zinc sulfate (a Zn ²⁺ source), and His‐NT3 (a neurotrophic factor). Within this system, sodium alginate forms reversible metal–ligand coordination bonds with Zn ²⁺ , while the His‐NT3 protein is integrated via affinity‐based interactions, contributing to localized retention and sustained therapeutic delivery. Experimental results demonstrate that this alginate‐based injectable hydrogel effectively modulates immune responses, promotes axonal regeneration, and concurrently enhances neurotransmitter‐associated synaptogenesis and remyelination. Furthermore, significant improvements were observed in the recovery of neurological functions, including motor function, sensory function, and bladder function. Collectively, these results demonstrate the promising potential of this alginate‐based injectable hydrogel for the treatment of traumatic SCI.