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Bio-Design and Manufacturing  2023 Vol.6 No.5 P.522535

http://doi.org/10.1007/s42242-023-00243-5


Microcurvature landscapes induce neural stem cell polarity and enhance neural differentiation


Author(s):  Ho-Yin Yuen, Wai-Sze Yip, Suet To & Xin Zhao

Affiliation(s):  Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China; more

Corresponding email(s):   sandy.to@polyu.edu.hk, xin.zhao@polyu.edu.hk

Key Words:  Curvature, Neural differentiation, Neurite outgrowth, Mechanotransduction


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Ho-Yin Yuen, Wai-Sze Yip, Suet To & Xin Zhao. Microcurvature landscapes induce neural stem cell polarity and enhance neural differentiation[J]. Journal of Zhejiang University Science D, 2023, 6(5): 522535.

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Abstract: 
Tissue curvature has long been recognized as an important anatomical parameter that affects intracellular behaviors, and there is emerging interest in applying cell-scale curvature as a designer property to drive cell fates for tissue engineering purposes. Although neural cells are known to undergo dramatic and terminal morphological changes during development and curvature-limiting behaviors have been demonstrated in neurite outgrowth studies, there are still crucial gaps in understanding neural cell behaviors, particularly in the context of a three-dimensional (3D) curvature landscape similar to an actual tissue engineering scaffold. In this study, we fabricated two substrates of microcurvature (curvature-substrates) that present a smooth and repeating landscape with focuses of either a concave or a convex pattern. Using these curvature-substrates, we studied the properties of morphological differentiation in N2a neuroblastoma cells. In contrast to other studies where two-dimensional (2D) curvature was demonstrated to limit neurite outgrowth, we found that both the concave and convex substrates acted as continuous and uniform mechanical protrusions that significantly enhanced neural polarity and differentiation with few morphological changes in the main cell body. This enhanced differentiation was manifested in various properties, including increased neurite length, increased nuclear displacement, and upregulation of various neural markers. By demonstrating how the micron-scale curvature landscape induces neuronal polarity, we provide further insights into the design of biomaterials utilizing the influence of surface curvature in neural tissue engineering.

香港理工大学赵昕杜雪课题组联合发表 | 微曲率结构诱导神经干细胞极性并增强神经分化

本研究论文聚焦于解析组织工程支架的连续微曲率结构对神经细胞行为的指导作用。长期以来,曲率一直被认为是影响细胞行为的重要构造参数,研究人员也逐渐对调节组织工程支架的微尺度曲率进而影响细胞命运产生兴趣。研究表明,神经细胞在发育过程中会发生剧烈的形态变化,并且曲率存在会对神经突生长起限制作用,但关于理解神经细胞如何受组织工程支架三维曲率影响仍存在较多空白。本研究中,作者制备了两种微曲率基板,分别为连续重复的凹面或凸面图案,进一步利用基板对N2a小鼠神经母细胞瘤细胞分化形态进行研究。结果表明,与之前报道的二维曲率限制神经突生长结论相比,连续的凹面或凸面图案均可显著增强神经细胞的极化和分化,且几乎不会引起细胞主体形态变化。神经细胞分化增强的特性,主要包括轴突增长、细胞核位移增加以及神经细胞标志物表达上调。通过理解微曲率结构影响神经元极化的方式,将为设计神经组织工程材料提供新的视角。

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