Magnetothermally responsive fibrin hydrogel for localized neuromodulation

Magnetic biointerfaces have emerged as powerful tools in neuroscience, enabling significant advances in both neural regeneration and neuromodulation. Magnetothermal neuromodulation using magnetic nanoparticles (MNPs) responsive to alternating magnetic fields (AMFs), offers a remote means of localized thermal stimulation of thermosensitive ion channels, which subsequently modulate neural activity, but clinical translation is limited by poor spatial control and off-target nanoparticle distribution. Here, we introduce a magnetically responsive fibrin hydrogel that spatially confines polyethylene glycol-functionalized iron oxide nanoparticles and enables localized magnetothermal stimulation in three-dimensional (3D) neural constructs. Incorporation of MNPs (3-10 mg/mL) yielded hybrid hydrogels with tunable morphology, mechanical properties, and degradation kinetics while generating temperature increases under AMFs. The magnetic fibrin hydrogel supported dorsal root ganglion explant viability (>95%) and promoted neurite outgrowth within a 3D matrix. When adhered to spinal cord tissue ex vivo, the hydrogels produced localized and concentration-dependent heating, demonstrating efficient heat transfer to neural tissue. These results establish fibrin-based magnetic hydrogels as a biocompatible platform for spatially controlled magnetothermal neuromodulation and suggest their potential as implantable interfaces for minimally invasive bioelectronic therapies.