Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells1-6 or used bioengineered constructs to arrange cells in an organ-like configuration7,8. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies. Microfilamentengineered cerebral organoids (enCORs) display enhanced neuroectoderm formation and improved cortical development. Furthermore, reconstitution of the basement membrane leads to characteristic cortical tissue architecture, including formation of a polarized cortical plate and radial units. Thus, enCORs model the distinctive radial organization of the cerebral cortex and allow for the study of neuronal migration. Our data demonstrate that combining 3D cell culture with bioengineering can increase reproducibility and improve tissue architecture.Correspondence should be addressed to M.A.L. mlancast@mrc

In the HTML and PDF versions of this article initially published, μ's appeared as m's throughout the scale bar lengths in the figure legends, as well as in the Methods section in the phrases "added to give a final volume of 150 μl per well, " "an average hPSC cell size of 15 μm" and "sectioned on a vibratome to collect 300-μm sections. " In the HTML version, μ's appeared as m's in all instances throughout the Methods section except "35 μg/ml of pure laminin" and "35 μl laminin/entactin + 25 μl collagen. " The errors have been corrected in the HTML and PDF versions of the article.