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Review
. 2025 May 1;32(5):689-709.
doi: 10.1016/j.stem.2025.03.014.

Bioengineering innovations for neural organoids with enhanced fidelity and function

Yubing Sun  1 , Yoshiho Ikeuchi  2 , Feng Guo  3 , Insoo Hyun  4 , Guo-Li Ming  5 , Jianping Fu  6
Affiliations
Review

Bioengineering innovations for neural organoids with enhanced fidelity and function

Yubing Sun et al. Cell Stem Cell. .

Abstract

Neural organoids have been utilized to recapitulate different aspects of the developing nervous system. While hailed as promising experimental tools for studying human neural development and neuropathology, current neural organoids do not fully recapitulate the anatomy or microcircuitry-level functionality of the developing brain, spinal cord, or peripheral nervous system. In this review, we discuss emerging bioengineering approaches that control morphogen signals and biophysical microenvironments, which have improved the efficiency, fidelity, and utility of neural organoids. Furthermore, advancements in bioengineered tools have facilitated more sophisticated analyses of neural organoid functions and applications, including improved neural-bioelectronic interfaces and organoid-based information processing. Emerging bioethical issues associated with advanced neural organoids are also discussed. Future opportunities of neural organoid research lie in enhancing their fidelity, maturity, and complexity and expanding their applications in a scalable manner.

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Conflict of interest statement

Declaration of interests I.H., G.-l.M., and J.F. are advisory board members of Cell Stem Cell. The University of Michigan, Ann Arbor has filed a patent application describing microfluidic devices and methods for the development of neural tube-like tissues and neural spheroids (PCT/US2021/058090), with J.F. as a co-inventor. The University of Massachusetts, Amherst has filed a patent application describing passive diffusion device for patterning neural organoids (US patent no. 18/625,271), with Y.S. as a co-inventor.

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