Sodium Alginate Hydrogel with Zinc Ion Nanoparticles for Synergistic Neuroprotection and Functional Recovery in Spinal Cord Injury

The current lack of effective treatments for traumatic spinal cord injury (SCI) presents a significant challenge in managing the complex microenvironmental alterations that follow the initial trauma. This study developed an injectable alginate hydrogel dynamically cross-linked by tannic acid–zinc nanoparticles (TA@Zn NPs), which exerts neuroprotective effects through the sustained release of zinc ions (Zn2+) and antioxidant TA@Zn NPs. TA@Zn NPs were cross-linked with phenylboronic acid-modified sodium alginate (SA) to form an injectable gel system. In response to the acidic and ROS-rich microenvironment characteristic of SCI, the hydrogel undergoes degradation, thereby triggering the disintegration of TA@Zn NPs and the concomitant release of Zn2+, enabling sustained therapeutic delivery. In a rat model of contusion injury, the degradation of TA@Zn NPs and the sustained release of Zn2+ significantly reduced oxidative damage and promoted axonal regeneration, which in turn inhibited scar formation and enhanced the tissue’s antioxidant capacity. Consequently, the group treated with the Zn2+-releasing hydrogel exhibited significant recovery of motor function. Collectively, these results validate the dual-function integration of Zn2+ as a dynamic cross-linker and neuroprotective agent within injectable hydrogels as a robust strategy for SCI repair, presenting a clinically translatable paradigm for neural regeneration.