Brain implantation of soft bioelectronics via embryonic development

Hao Sheng, Ren Liu, Qiang Li, Zuwan Lin, Yichun He, Thomas S. Blum, Hao Zhao, Xin Tang, Wenbo Wang, Lishuai Jin, Zheliang Wang, Emma Hsiao, Paul Le Floch, Hao Shen, Ariel J. Lee, Rachael Alice Jonas-Closs, James Briggs, Siyi Liu, Daniel Solomon, Xiao Wang, Jessica L. Whited, Nanshu Lu and Jia Liu ()
Additional contact information
Hao Sheng: Harvard University
Ren Liu: Harvard University
Qiang Li: Harvard University
Zuwan Lin: Harvard University
Yichun He: Harvard University
Thomas S. Blum: Harvard University
Hao Zhao: Harvard University
Xin Tang: Harvard University
Wenbo Wang: Harvard University
Lishuai Jin: University of Pennsylvania
Zheliang Wang: The University of Texas at Austin
Emma Hsiao: Harvard University
Paul Le Floch: Harvard University
Hao Shen: Harvard University
Ariel J. Lee: Harvard University
Rachael Alice Jonas-Closs: Harvard Medical School
James Briggs: Broad Institute of MIT and Harvard
Siyi Liu: The University of Texas at Austin
Daniel Solomon: Harvard University
Xiao Wang: Broad Institute of MIT and Harvard
Jessica L. Whited: Harvard University
Nanshu Lu: The University of Texas at Austin
Jia Liu: Harvard University

Nature, 2025, vol. 642, issue 8069, 954-964

Abstract: Abstract Developing bioelectronics capable of stably tracking brain-wide, single-cell, millisecond-resolved neural activity in the developing brain is critical for advancing neuroscience and understanding neurodevelopmental disorders. During development, the three-dimensional structure of the vertebrate brain arises from a two-dimensional neural plate1,2. These large morphological changes have previously posed a challenge for implantable bioelectronics to reliably track neural activity throughout brain development3–9. Here we introduce a tissue-level-soft, submicrometre-thick mesh microelectrode array that integrates into the embryonic neural plate by leveraging the tissue’s natural two-dimensional-to-three-dimensional reconfiguration. As organogenesis progresses, the mesh deforms, stretches and distributes throughout the brain, seamlessly integrating with neural tissue. Immunostaining, gene expression analysis and behavioural testing confirm no adverse effects on brain development or function. This embedded electrode array enables long-term, stable mapping of how single-neuron activity and population dynamics emerge and evolve during brain development. In axolotl models, it not only records neural electrical activity during regeneration but also modulates the process through electrical stimulation.

Date: 2025
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DOI: 10.1038/s41586-025-09106-8

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