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

Abstract

Spinal cord injury (SCI) is a devastating trauma to the central nervous system, causing permanent functional nerve defects. A key therapeutic challenge is the inhibition of the secondary injury cascade, specifically the progressive neural damage from iron overload-induced ferroptosis and oxidative stress. To target these dual mechanisms, we developed a dual-functional, iron-scavenging, and hydrogen-releasing microneedle patch (MN/MON@AB) composed of ammonia borane (AB)-loaded, amino-functionalized mesoporous organosilica nanoparticles (MON-NH₂) embedded in a biodegradable silk fibroin array. This system functions via a dual-target mechanism: amino groups chelate excess iron ions to suppress the Fenton reaction, while AB provides sustained release of molecular hydrogen (H₂) in the acidic injury microenvironment to neutralize reactive oxygen species (ROS). MN/MON@AB has been found to reduce the intracellular Fe²⁺ levels by 46.7%, nearly doubling the expression of the key ferroptosis regulator GPX4, and largely alleviating lipid peroxidation <i>in vitro</i>. In a murine SCI model, the patch significantly reduced spinal iron deposition (<i>p</i> < 0.0001) and promoted marked locomotor recovery (<i>p</i> < 0.001). Featuring combined localized iron chelation and sustained antioxidant delivery, the present strategy offers a broadly applicable and pioneering therapeutic platform for treating acute neural injuries and subsequent neurodegenerative processes.