Multifunctional Core-Shell Structured Manganese Nanozyme Incorporated Hydrogel for Spinal Cord Injury Microenvironment Reconstruction

Spinal cord injury (SCI) leads to motor and sensory loss due to damage to the spinal cord's nerve fibers. Secondary inflammation and excessive reactive oxygen species (ROS) create a hostile environment for regeneration. To address oxidative stress and inflammation simultaneously, we developed a composite QUE-Mn3O4@PDA-GelMA hydrogel that integrates ROS-scavenging activity of Mn3O4 nanozyme with the anti-inflammatory properties of quercetin within a photocrosslinkable GelMA hydrogel matrix. Mn3O4 nanozymes were synthesized and encapsulated via dopamine polymerization, then functionalized with quercetin to form Mn3O4@PDA-GelMA, which was subsequently embedded in GelMA and crosslinked. Further, structural and physicochemical characterization confirmed successful PDA coating, crystallinity consistent with Mn3O4, and uniform nanoparticle distribution. Additionally, the composite hydrogel exhibited suitable mechanical properties and degradation behavior for spinal tissue mimicry. In vitro assays demonstrated that the hydrogel effectively scavenged ROS, reduced pro-inflammatory macrophage polarization, and maintained neural cell viability at the selected concentration. These combined effects suggest that the hydrogel creates a more favorable microenvironment for neural protection and potential regeneration. Therefore, the QUE-Mn3O4@PDA-GelMA hydrogel provides a suitable environment for neural regeneration that concurrently attenuates oxidative stress and inflammation, positioning it as a promising candidate for enhancing SCI repair.