A Janus Mg 2+ and H 2 Pump Conduit for Enhanced Peripheral Nerve Regeneration

Abstract Peripheral nerve injuries, often caused by trauma and tumor resection, severely impair motor and sensory functions. While autologous nerve grafting remains the gold standard, its efficiency is hindered by limited donor tissue availability, donor site morbidity, and neuropathic pain. Tissue‐engineered nerve grafts, emerging as promising alternatives, still face challenges due to the lack of essential biochemical and biophysical cues for comprehensive nerve regeneration. This study introduces a Janus Mg 2+ /H 2 pump conduit, constructed with a MgH 2 @PLGA middle layer, polycaprolactone (PCL) outer layers, and a polydopamine‐coated PCL (PCL@PDA) inner layer. The PCL provides structural support, while the MgH 2 @PLGA layer continuously releases Mg 2+ and H 2 as biochemical cues, driven by an acidic microenvironment and the MgH 2 ‐water reaction. PDA modification of the inner layer, serving as biophysical cues, further increases cell adhesion. Mg 2+ released from the conduit mitigates oxidative stress in Schwann cells and increases their expression of neurotrophic factors, while the H 2 attenuates inflammation, aiding nerve regeneration. In a rat sciatic nerve defect model, the conduit shows enhanced functional, electrophysiological, and histological recovery. These findings highlight the potential of Janus Mg 2+ /H 2 pump conduit as a promising approach for peripheral nerve defect repair by offering a conducive microenvironment.