Background Anisotropic topologies are known to regulate cell-oriented growth and induce cell differentiation, which is conducive to accelerating nerve regeneration, while co-culture of endothelial cells (ECs) and Schwann cells (SCs) can significantly promote the axon growth of dorsal root ganglion (DRG). However, the synergistic regulation of EC and SC co-culture of DRG behavior on anisotropic topologies is still rarely reported. The study aims to investigate the effect of anisotropic topology co-cultured with Schwann cells and endothelial cells on dorsal root ganglion behavior for promoting peripheral nerve regeneration. Methods Chitosan/artemisia sphaerocephala (CS/AS) scaffolds with anisotropic topology were first prepared using micro-molding technology, and then the surface was modified with dopamine to facilitate cell adhesion and growth. The physical and chemical properties of the scaffolds were characterized through morphology, wettability, surface roughness and component variation. SCs and ECs were co-cultured with DRG cells on anisotropic topology scaffolds to evaluate the axon growth behavior. Results Dopamine-modified topological CS/AS scaffolds had good hydrophilicity and provided an appropriate environment for cell growth. Cellular immunofluorescence showed that in contrast to DRG growth alone, co-culture of SCs and ECs could not only promote the growth of DRG axons, but also offered a stronger guidance for orientation growth of neurons, which could effectively prevent axons from tangling and knotting, and thus may significantly inhibit neurofibroma formation. Moreover, the co-culture of SCs and ECs could promote the release of nerve growth factor and vascular endothelial growth factor, and up-regulate genes relevant to cell proliferation, myelination and skeletal development via the PI3K-Akt, MAPK and cytokine and receptor chemokine pathways. Conclusions The co-culture of SCs and ECs significantly improved the growth behavior of DRG on anisotropic topological scaffolds, which may provide an important basis for the development of nerve grafts in peripheral nerve regeneration.

中文翻译：

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雪旺细胞和内皮细胞的共培养协同调节壳聚糖基各向异性拓扑的背根神经节行为，用于周围神经再生。

背景 各向异性拓扑可调节细胞定向生长并诱导细胞分化，有利于加速神经再生，而内皮细胞（ECs）和雪旺细胞（SCs）共培养可显着促进背根神经节轴突生长(DRG)。然而，EC和SC共培养DRG行为对各向异性拓扑的协同调节仍然很少报道。本研究旨在探讨各向异性拓扑与雪旺细胞和内皮细胞共培养对促进周围神经再生的背根神经节行为的影响。方法首先采用微成型技术制备具有各向异性拓扑结构的壳聚糖/青蒿(CS/AS)支架，然后用多巴胺修饰表面以促进细胞粘附和生长。通过形态、润湿性、表面粗糙度和成分变化来表征支架的物理和化学性质。SCs 和 ECs 与 DRG 细胞在各向异性拓扑支架上共培养，以评估轴突生长行为。结果多巴胺修饰的拓扑CS/AS支架具有良好的亲水性，为细胞生长提供了适宜的环境。细胞免疫荧光显示，与单独的DRG生长相比，SCs和ECs共培养不仅可以促进DRG轴突的生长，还可以为神经元的定向生长提供更强的指导，可以有效防止轴突缠结和打结，因此可以显着抑制神经纤维瘤的形成。而且，SCs和ECs共培养可以促进神经生长因子和血管内皮生长因子的释放，并通过PI3K-Akt、MAPK和细胞因子和受体趋化因子通路上调与细胞增殖、髓鞘形成和骨骼发育相关的基因。结论 SCs和ECs共培养显着改善了DRG在各向异性拓扑支架上的生长行为，可能为周围神经再生神经移植物的发展提供重要依据。