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Peripheral nerve defects present significant clinical challenges due to the limited regenerative capacity of nerve tissues and the inefficacy of existing treatment methods. Magnesium-based biomaterials have shown promise in nerve regeneration by releasing Mg²⁺ ions, which enhance Schwann cell function and axonal growth. However, their rapid Mg²⁺ release significantly limits long-term regenerative effects. To address this issue, this study focuses on developing a multi-gradient electrospun nanofiber scaffold with a controlled and sustained Mg²⁺ release profile to improve nerve repair outcomes, utilizing an electrospinning machine to precisely engineer fiber structures.
To achieve this, an electrospinning machine was used to fabricate MgO/MgCO₃/polycaprolactone (PCL) nanofiber membranes, designed to provide a tunable release of Mg²⁺ over time. These membranes were structurally and chemically characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and contact angle measurements. The biological effects of Mg²⁺ were evaluated through in vitro studies, where dorsal root ganglia (DRG) neurons and Schwann cells were cultured to assess neurite outgrowth, cell proliferation, migration, and phenotypic transformation. Additionally, CCK-8 assays and cell scratch tests were used to quantify Schwann cell activity, while western blot analysis and transcriptome sequencing helped elucidate the molecular pathways, particularly the role of Wnt signaling. The in vivo efficacy of the scaffold was tested using a 10 mm sciatic nerve defect model in rats, where MgO/MgCO₃/PCL fibers, produced by an electrospinning machine, were integrated into a 3D-engineered PCL nerve conduit. The success of nerve repair was then assessed through histological staining, transmission electron microscopy (TEM), and gait analysis.
The study demonstrated that the MgO/MgCO₃/PCL scaffold, fabricated using an electrospinning machine, sustained Mg²⁺ release for up to 6 weeks, providing continuous support for nerve regeneration. This sustained Mg²⁺ delivery significantly enhanced Schwann cell function by promoting proliferation, migration, and transition to a repair phenotype, which in turn facilitated axonal regrowth and myelination. Furthermore, western blot and transcriptomic analysis identified the activation of the Wnt5a/β-Catenin signaling pathway as a key mechanism underlying Mg²⁺-induced Schwann cell function enhancement. In vivo studies confirmed that the 10% MgO/MgCO₃/PCL scaffold achieved the best regenerative outcomes, balancing effective Mg²⁺ release with biocompatibility, whereas higher concentrations (30%) led to excessive inflammatory responses, highlighting the importance of optimal Mg²⁺ levels for nerve repair.
This study introduces a multi-gradient electrospun MgO/MgCO₃/PCL nanofiber scaffold, produced using an electrospinning machine, offering a novel strategy for precisely controlled Mg²⁺ release, extending its therapeutic effect beyond what previous magnesium-based biomaterials achieved. By ensuring sustained Mg²⁺ availability for long-term nerve regeneration, the study overcomes the limitations of rapid ion release seen in earlier designs. Additionally, it reveals a molecular mechanism—Wnt5a/β-Catenin signaling—by which Mg²⁺ enhances Schwann cell function, providing deeper insights into the biological role of magnesium in nerve repair. These findings not only pave the way for clinical translation of magnesium-based scaffolds but also establish a foundation for designing more effective biomaterials for peripheral nerve injury treatment.
Electrospinning Nanofibers Article Source:
https://doi.org/10.1007/s42765-024-00489-3
