Electrospinning Multilayered Scaffolds Loaded with Melatonin and Fe3O4 Magnetic Nanoparticles for Peripheral Nerve Regeneration

Peripheral nerve injury is a common clinical problem bringing heavy burden to patients, due to its high incidence and unsatisfactory treatment. Nerve guidance conduit (NGC) is a promising scaffold for peripheral nerve repair, and bioactive agents are applied for great functional recovery. Melatonin (MLT) and Fe3O4 magnetic nanoparticles (Fe3O4‐MNPs) are proven to inhibit oxidative stress, inflammation, and induce nerve regeneration. Herein, a multilayered composite NGC loaded with MLT and Fe3O4‐MNPs is designed for sequential and sustainable drug release, creating an appropriate microenvironment for nerve regeneration. The composite scaffold shows sufficient mechanical strength and biocompatibility in vitro, and evidently promotes morphological, functional, and electrophysiological recovery of regenerated sciatic nerves in vivo. This work proves that the multilayered conduits show great prospect in the long‐term nerve defects treatment due to easy manufacture and desired efficacy. A multilayered composite scaffold loaded with melatonin (MLT) and Fe3O4‐MNPs is fabricated by electrospinning, which possesses good biocompatibility and proper stiffness. MLT inhibits oxidative stress and inflammation, while Fe3O4‐MNPs induces neurite regrowth. Sequential and sustainable release of bioactive agents provides an appropriate microenvironment for the long‐term treatment of nerve transections, showing great performance in nerve regeneration and functional recovery.