Human pluripotent stem cells have emerged as a promising in vitro model system for studying the brain. Two-dimensional and three-dimensional cell culture paradigms have provided valuable insights into the pathogenesis of neuropsychiatric disorders, but they remain limited in their capacity to model certain features of human neural development. Specifically, current models do not efficiently incorporate extracellular matrix-derived biochemical and biophysical cues, facilitate multicellular spatio-temporal patterning, or achieve advanced functional maturation. Engineered biomaterials have the capacity to create increasingly biomimetic neural microenvironments, yet further refinement is needed before these approaches are widely implemented. This Review therefore highlights how continued progression and increased integration of engineered biomaterials may be well poised to address intractable challenges in recapitulating human neural development.

人类多能干细胞已成为研究大脑的有前途的体外模型系统。二维和三维细胞培养范式为神经精神疾病的发病机制提供了宝贵的见解，但它们在模拟人类神经发育的某些特征的能力方面仍然有限。具体来说，目前的模型不能有效地结合细胞外基质衍生的生化和生物物理线索，促进多细胞时空模式，或实现先进的功能成熟。工程生物材料有能力创造越来越多的仿生神经微环境，但在这些方法被广泛实施之前，还需要进一步改进。