Abstract

Restoring motor function remains a primary goal in the treatment of spinal cord injury (SCI). However, the inflammatory microenvironment that develops after injury poses a significant barrier to effective neural repair. Addressing this challenge requires the development of bioactive scaffolds with potent anti-inflammatory and antioxidant properties, as well as reduced implantation-induced damage. In this study, we created a novel composite biomaterial scaffold with high mechanical strength and excellent anti-inflammatory and antioxidant capabilities by dispersing in situ self-assembled tea polyphenol-magnesium nanoparticles (TPs-Mg NPs) into gelatin methacryloyl hydrogel (GelMA) microneedle patches (TPs-Mg MN). Our results demonstrate that TPs-Mg MN effectively modulates the inflammatory response by promoting macrophage polarization through suppression of the NF-κB signaling pathway, thereby alleviating reactive oxygen species (ROS)-mediated oxidative damage. Following implantation in a rat SCI model, TPs-Mg MN significantly enhanced motor functional recovery. Behavioral analyses revealed that this recovery was achieved through multiple mechanisms, including reduced oxidative stress, inflammation, and scar formation at the injury site, as well as enhanced angiogenesis and neurogenesis within the spinal cord tissue. This study presents a multifunctional combinatorial strategy for mitigating ROS-induced oxidative stress, offering broad potential applications in SCI and other central nervous system disorders.