An Iron-Scavenging and Hydrogen-Releasing Microneedle Patch Suppresses Ferroptosis and Promotes Spinal Cord Repair.

Abstract

Spinal cord injury (SCI) triggers a secondary damage cascade driven by iron overload-induced ferroptosis and oxidative stress. To address these dual pathological mechanisms, researchers constructed a microneedle patch (MN/MON@AB) incorporating ammonia borane (AB)-loaded, amino-functionalized mesoporous organosilica nanoparticles embedded within a biodegradable silk fibroin matrix. The amino functional groups chelate excess iron ions, thereby inhibiting the Fenton reaction, while AB releases molecular hydrogen (H2) continuously under the acidic conditions of the injury microenvironment to scavenge reactive oxygen species. In vitro evaluation showed a 46.7% reduction in intracellular Fe2+ levels, approximately a twofold increase in GPX4 expression, and marked attenuation of lipid peroxidation. In a murine SCI model, the patch significantly decreased spinal iron deposition (p < 0.0001) and facilitated locomotor recovery (p < 0.001), demonstrating the potential of localized iron chelation combined with sustained antioxidant hydrogen delivery for acute neural injury.

Mechanism

Amino groups on the nanoparticles chelate excess Fe2+ to block the Fenton reaction, while ammonia borane releases H2 under acidic injury conditions to neutralize ROS, collectively preventing ferroptosis and restoring GPX4 expression.