DFO biofunctionalized CaTiO₃@CS/SF-DFO scaffolds for regulating Schwann cells and dorsal root ganglion behaviors

Peripheral nerve injury (PNI) repair faces great hurdles. Autologous nerve grafts, the clinical gold standard, suffer from donor shortage and secondary injury, while traditional nerve conduits yield unsatisfactory regeneration. Herein, we fabricated an electrospun anisotropic chitosan/silk fibroin scaffold embedded with calcium titanate nanoparticles (CTO@CS/SF), modified by dopamine to conjugate deferoxamine (DFO) for PNI treatment. We fully characterized the scaffold's microstructure, wettability, mechanical properties and degradability, and evaluated its bioactivity via Schwann cells (SCs), dorsal root ganglia (DRG) and endothelial cells. Highly aligned fibers and elevated hydrophilicity were observed in DFO-loaded samples. The 5% DFO group greatly boosted proliferation, migration and spreading of RSC96 cells, and induced longer oriented axonal extension of DRG neurons. Mechanically, DFO upregulated YAP (proliferation/migration) and EGR2 (myelination), driving SCs toward a myelinating phenotype. This DFO-functionalized CTO@CS/SF biomaterial offers a promising candidate for peripheral nerve regenerative therapy.