Abstract

As an important application of functional biomaterials, neural probes have contributed substantially to studying the brain. Bioinspired and biomimetic strategies have begun to be applied to the development of neural probes, although these and previous generations of probes have had structural and mechanical dissimilarities from their neuron targets that lead to neuronal loss, neuroinflammatory responses and measurement instabilities. Here, we present a bioinspired design for neural probes—neuron-like electronics (NeuE)—where the key building blocks mimic the subcellular structural features and mechanical properties of neurons. Full three-dimensional mapping of implanted NeuE–brain interfaces highlights the structural indistinguishability and intimate interpenetration of NeuE and neurons. Time-dependent histology and electrophysiology studies further reveal a structurally and functionally stable interface with the neuronal and glial networks shortly following implantation, thus opening opportunities for next-generation brain–machine interfaces. Finally, the NeuE subcellular structural features are shown to facilitate migration of endogenous neural progenitor cells, thus holding promise as an electrically active platform for transplantation-free regenerative medicine.

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The code used for data analysis is available from the corresponding author upon reasonable request.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank D. Richardson and S. Terclavers for help with image acquisition, data handling and critical discussion, and J. Huang for assistance with recording instrumentation. This work is supported by the National Institute on Drug Abuse of the National Institutes of Health (1R21DA043985-01), a NIH Director’s Pioneer Award (1DP1EB025835-01) and the Air Force Office of Scientific Research (FA9550-14-1-0136) (to C.M.L.), the Simmons Awards (to X.Y.) and an American Heart Association Postdoctoral Fellowship (16POST27250219) and NIH Pathway to Independence Award (1K99AG056636-02) (to G.H.). This work was performed in part at the Harvard Center for Biological Imaging (HCBI) and Harvard University Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI) supported by the National Science Foundation.

Author information

Author notes

  1. These authors contributed equally: Xiao Yang, Tao Zhou, Theodore J. Zwang.

Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA

    • Xiao Yang
    • , Tao Zhou
    • , Theodore J. Zwang
    • , Guosong Hong
    • , Yunlong Zhao
    • , Tian-Ming Fu
    • , Teng Gao
    •  & Charles M. Lieber
  2. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    • Robert D. Viveros
    •  & Charles M. Lieber
  3. Center for Brain Science, Harvard University, Cambridge, MA, USA

    • Charles M. Lieber

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Contributions

X.Y. and C.M.L. designed the experiments. X.Y., T.Z., T.J.Z., G.H., Y.Z., R.D.V., T.-M.F. and T.G. performed the experiments. X.Y., T.Z., T.J.Z. and C.M.L. analysed the data. X.Y. and C.M.L. wrote the paper. All authors discussed the results, revised or commented on the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Charles M. Lieber.

Supplementary information

  1. Supplementary Information

    Supplementary Notes, Supplementary Figures 1–21, Supplementary Tables 1–3, Supplementary Video Legends 1–3, Supplementary References

  2. Reporting Summary

  3. Supplementary Video 1

    Full 3D NeuE/neuron interface—360°-rotation video of the full 3D NeuE/neuron interface shown in Fig. 1d. Green and red colours represent neurons and NeuE, respectively.

  4. Supplementary Video 2

    Structurally indistinguishable NeuE/neuron interface—video showing depth-coding structures corresponding to Fig. 1f(II), highlighting structural indistinguishability between neuron neurites and NeuE neurite-like interconnects.

  5. Supplementary Video 3

    Junction between neuron neurites and NeuE neurite-like interconnect—video showing channel-coding and depth-coding structures corresponding to Fig. 1f(III),(IV), highlighting closely contacted junction between neuron neurites and NeuE neurite-like interconnect.

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DOI

https://doi.org/10.1038/s41563-019-0292-9