The emerging role of magnesium in peripheral nerve regeneration: biomaterial design, mechanistic basis, and translational barriers.

Peripheral nerve injuries (PNIs) affect over 5% of patients worldwide who experience trauma, surgical complications, or metabolic disorders, leading to long-term disability and a significant socioeconomic burden. Current treatments include direct repair with various grafts or implantation of nerve conduits; however, autologous nerve grafting remains the gold standard. The limitations of existing options, particularly donor-site morbidity and limited availability of autologous nerve grafts, have increased interest in biomaterial-based strategies for nerve regeneration. Among emerging candidates, magnesium (Mg) has gained attention for its inherent biocompatibility, biodegradability, and well-established neuro-regenerative properties. Recently, Mg-based biomaterials have demonstrated promise by providing multiple functions, from mechanical support to injury repair, by promoting axonal growth, Schwann cell activity, angiogenesis, and modulation of key neuroinflammation pathways critical for Mg-based biomaterial-mediated nerve regeneration. In parallel, advances in material design, such as alloying, surface modification, and composite fabrication, have enabled improved control over Mg corrosion behavior, mechanical properties, and ion release kinetics, thereby enhancing biological performance and safety. Despite these advantages, research on Mg-based approaches for nerve regeneration is still in its early stages, with no clinical studies reported to date. Concerns about long-term biocompatibility and safety remain. This review highlights recent progress, underlying mechanisms, and translational opportunities for Mg-based strategies in peripheral nerve repair. It also addresses current knowledge gaps and suggests potential solutions, offering new directions for future research.