Revolutionizing role of magnetic field-guided MnFe2O4@ZIF-8@retinoic acid in DUCA conduits for inflammation inhibition and peripheral nerve regeneration

Abstract

Neuroma formation following the repair of nerve injuries exceeding 0.9 cm in length severely impedes functional recovery. To overcome this challenge, we engineered magnetically responsive core-shell nanoparticles (MnFe₂O₄@ZIF-8@Retinoic acid, MFZR; 90–360 nm) to guide regeneration within a decellularized umbilical cord artery (DUCA) conduit. We investigated the synergistic effect of MFZR under an external magnetic field (MF) on Schwann cell behavior in vitro and on sciatic nerve repair in a rat model. Under MF exposure, MFZR significantly enhanced Schwann cell migration, alignment, and elongation on DUCA conduits. In-vivo, the MFZR+MF combination potently promoted functional recovery, as measured by the sciatic functional index, muscle compound action potential, and nerve conduction velocity, without inducing DUCA-related inflammation. Histological analysis demonstrated robust regeneration, characterized by increased axon diameter, an improved G-ratio, and elevated expression of S100 and NF-200. This regeneration was facilitated by a healing-promoting M2 macrophage polarization at the injury site. Critically, the strategy exhibited no systemic toxicity. These findings establish that magnetically guided MFZR effectively prevents neuroma in the DUCA conduits, orchestrates a pro-regenerative microenvironment, and achieves significant functional recovery, offering a promising translatable strategy for nerve repair.