大脑类器官（CO）源自人类在体外诱导的多能干细胞，模仿人类胎儿大脑的特征。 CO的发展很大程度上依赖于“自组织”机制，其中分化为皮质细胞的细胞自主组织成大脑皮质样组织。然而，对其形态（包括尺寸和厚度）的外在操纵仍然具有挑战性。在这项研究中，我们发现硅酸盐微纤维支架可以支持皮质神经元层的形成，并在70天内成功生成了比传统CO厚9倍的皮质神经元层。硅酸盐微纤维层中的这些皮质神经元以类似胎儿大脑的层状图案分化。虽然这些细胞特征（例如皮质神经元和神经干/祖细胞）与传统 CO 的细胞特征相似，但皮质神经元层在片状结构中大大增厚。此外，支架中的皮质神经元表现出自发的电活动。我们得出的结论是，硅酸盐微纤维支架支持 CO 皮质神经元层的形成，而不干扰自组织驱动的皮质生成。对 CO 皮质神经元层形成的外在操纵可能有助于研究人类大脑皮层的发育机制或发病机制，特别是对于再生疗法和生物工程的发展。© 作者 2023。出版者牛津大学出版社。

Cerebral organoids (COs) are derived from human-induced pluripotent stem cells in vitro and mimic the features of the human fetal brain. The development of COs is largely dependent on "self-organization" mechanisms, in which differentiating cells committed to cortical cells autonomously organize into the cerebral cortex-like tissue. However, extrinsic manipulation of their morphology, including size and thickness, remains challenging. In this study, we discovered that silicate microfiber scaffolds could support the formation of cortical neuronal layers and successfully generated cortical neuronal layers, which are 9 times thicker than conventional COs, in 70 days. These cortical neurons in the silicate microfiber layer were differentiated in a fetal brain-like lamination pattern. While these cellular characteristics such as cortical neurons and neural stem/progenitor cells were like those of conventional COs, the cortical neuronal layers were greatly thickened in sheet-like configuration. Moreover, the cortical neurons in the scaffolds showed spontaneous electrical activity. We concluded that silicate microfiber scaffolds support the formation of the cortical neuronal layers of COs without disturbing self-organization-driven corticogenesis. The extrinsic manipulation of the formation of the cortical neuronal layers of COs may be useful for the research of developmental mechanisms or pathogenesis of the human cerebral cortex, particularly for the development of regenerative therapy and bioengineering.© The Author(s) 2023. Published by Oxford University Press.