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Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity

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Abstract

The complex structure and function of the human central nervous system that develops from the neural tube made in vitro modeling quite challenging until the discovery of brain organoids. Human-induced pluripotent stem cells–derived brain organoids offer recapitulation of the features of early human neurodevelopment in vitro, including the generation, proliferation, and differentiation into mature neurons and micro-macroglial cells, as well as the complex interactions among these diverse cell types of the develo** brain. Recent advancements in brain organoids, microfluidic systems, real-time sensing technologies, and their cutting-edge integrated use provide excellent models and tools for emulation of fundamental neurodevelopmental processes, the pathology of neurological disorders, personalized transplantation therapy, and high-throughput neurotoxicity testing by bridging the gap between two-dimensional models and the complex three-dimensional environment in vivo. In this review, we summarize how bioengineering approaches are applied to mitigate the limitations of brain organoids for biomedical and clinical research. We further provide an extensive overview and future perspectives of the humanized brain organoids-on-chip platforms with integrated sensors toward brain organoid intelligence and biocomputing studies. Such approaches might pave the way for increasing approvable clinical applications by solving their current limitations.

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Funding

This work is supported by the Scientific and Technological Research Council (TUBITAK) of Turkey through 119M578. This study is partially conducted under the OrChESTRA (Organ-on-a-Chip Focused Strategic Partnership) project, which has received funding from the European Union’s Horizon Europe’s research and innovation program under Grant Agreement No. 101079473. P.S-M. gratefully acknowledges the TUBITAK 2211-A National Graduate Scholarship Program and 2214-A International Doctoral Research Fellowship Program.

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Authors and Affiliations

  1. Department of Bioengineering, Faculty of Engineering, Ege University, Izmir, Turkey

    Pelin Saglam-Metiner & Ozlem Yesil-Celiktas

  2. Department of Translational Neuroscience, Division of Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Pelin Saglam-Metiner & Onur Basak

  3. Department of Mechanical Engineering, Middle East Technical University, Ankara, Turkey

    Ender Yildirim

  4. ODTÜ MEMS Center, Ankara, Turkey

    Ender Yildirim

  5. Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg, Germany

    Can Dincer

  6. FIT Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Freiburg, Germany

    Can Dincer

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Saglam-Metiner, P., Yildirim, E., Dincer, C. et al. Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity. Microchim Acta 191, 71 (2024). https://doi.org/10.1007/s00604-023-06165-4

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