背景:脊髓损伤(SCI)诱导神经元死亡并破坏神经纤维束,导致严重的神经功能障碍甚至永久性瘫痪.将仿生纳米材料支架与神经干细胞(NSC)移植相结合的策略有望用于SCI治疗。方法:通过定向静电纺丝和随后的气体发泡处理相结合,设计和开发了创新的三维(3D)纳米纤维海绵(NSs)。免疫荧光,mRNA测序,磁共振成像,电生理分析,和行为测试用于研究3DNS的体外和体内再生作用。结果:生成的3DNS具有单轴排列的纳米结构和高度可控的分层结构,具有超高的孔隙率(99%),杰出的亲水性,合理的机械性能。它们促进细胞浸润,诱导细胞排列,促进神经干细胞的神经元分化,并通过细胞粘附分子途径促进其成熟。在体内,在大鼠SCI模型中,NSC接种的3DNSs有效促进轴突神经支配和髓鞘再生,随着新的“神经继电器”在病变间隙的发展。这些组织学变化与功能的恢复有关,包括增加SCI大鼠的神经运动评分,从大约2到16(共21个),并将胶带测试中的感测时间从140s减少到36s。此外,支架导致了上升和下降的电生理信号的恢复。结论:制作的3DNS有效地调节了NSC的命运,3DNS设计和移植神经干细胞的先进组合使其能够用作SCI修复的理想组织工程支架。
Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis. A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment. Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs. Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance. They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways. In vivo, the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new \"neural relays\" developing across the lesion gap. These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s. Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling. Conclusion: The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.