Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs.将超顺磁性氧化铁纳米颗粒（superparamagnetic iron oxide nanoparticles, SPIONs）与静电纺丝纤维（electrospun fibers）相结合制备的磁性纤维复合材料，在组织工程领域展现出良好的应用前景。通过在静电纺丝后对纤维进行可控接枝SPIONs，可在不改变纤维原有理想形貌的前提下制备生物相容性磁性复合材料。本研究首次探讨了结合磁场的SPION接枝支架促进神经突生长的潜力：该支架可借助排列有序纤维提供接触引导，并通过磁场中SPIONs产生机械刺激。本研究以培养于排列有序的对照纤维、SPION接枝静电纺丝纤维，以及培养基中分散有SPIONs的未接枝纤维上的原代大鼠背根神经节（dorsal root ganglia, DRG）外植体为对象，评估其神经突生长情况。为筛选促进神经突生长的最优磁场刺激方案，本研究构建了静态、交变及线性移动三种磁场环境，并随时间模拟支架不同区域的磁通密度分布。相较于静态磁场，交变磁场可使对照纤维上的神经突长度提升40%。此外，相较于在培养基中添加游离SPIONs的聚乳酸（poly(L-lactic acid), PLLA）纤维上培养的DRG外植体，交变磁场刺激可使SPION接枝纤维上的神经突长度提升30%、神经突面积提升62%。上述研究结果表明，相较于游离分散的SPIONs，结合磁场的SPION接枝纤维复合材料更有助于在静电纺丝纤维上促进神经突生长。