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Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces

Nature Biomedical Engineering volume 4, pages 1010–1022 (2020)Cite this article

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Abstract

Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand prototyping of customized electrode arrays well adjusted to specific anatomical environments, functions and experimental models. We also show, with the monitoring and activation of neuronal pathways in the brain, spinal cord and neuromuscular system of cats, rats and zebrafish, that the printed bioelectronic interfaces allow for long-term integration and functional stability. This technology might enable personalized bioelectronics for neuroprosthetic applications.

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Fig. 1: Rapid prototyping of soft electrode implants for interfacing the neuromuscular system.
Fig. 2: Printing and mechanical properties of planar electrode arrays.
Fig. 3: Electromechanical properties.
Fig. 4: Neuromodulation of the locomotor circuitry using NeuroPrint technology.
Fig. 5: Multi-nodal activation and monitoring of the neuromuscular system using NeuroPrint technology.
Fig. 6: Biointegration of NeuroPrint electrode arrays.
Fig. 7: Functional stability of NeuroPrint electrode arrays.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information file. The raw and analysed datasets generated during the study are too large to be publicly shared, but they are available for research purposes from the corresponding authors on reasonable request.

Code availability

The code used to program the printer paths can be found at https://sourceforge.net/projects/g-code-processor.

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Acknowledgements

We acknowledge funding from the following sources: the European Research Council (804005; IntegraBrain), Saint-Petersburg State University (project 51134206; funding to O.G. and N.M. for animal facility and biocompatibility studies, and validation of the implants on in vivo models), Technische Universität Dresden, the Russian Foundation for Basic Research (grants 20-015-00568-a (for the urodynamic study) and 18-33-20062-mol_a_ved (for developing the optimal electrode array configuration)), Deutsche Forschungsgemeinschaft (MI 2117/1-1) and the Volkswagen Foundation (Freigeist 91 690). We thank D. E. Korzhevskiy (immunohistochemistry), Y. I. Sysoev (zebrafish model), A. V. Goriainova (functional tests) and T. Kurth (electron microscopy) for help and expertise.

Author information

Author notes

  1. These authors contributed equally: Dzmitry Afanasenkau, Dana Kalinina.

  2. These authors jointly supervised this work: Ivan R. Minev, Pavel Musienko.

Authors and Affiliations

  1. Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, Germany

    Dzmitry Afanasenkau, Christoph Tondera, Seyyed Moosavi & Ivan R. Minev

  2. Institute of Translational Biomedicine, Saint-Petersburg State University, Saint-Petersburg, Russia

    Daria Kalinina, Oleg Gorsky, Natalia Pavlova, Natalia Merkulyeva, Allan V. Kalueff & Pavel Musienko

  3. Pavlov Institute of Physiology, Russian Academy of Sciences, Saint-Petersburg, Russia

    Vsevolod Lyakhovetskii, Oleg Gorsky, Natalia Pavlova, Natalia Merkulyeva & Pavel Musienko

  4. Granov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of the Russian Federation, Saint-Petersburg, Russia

    Vsevolod Lyakhovetskii, Oleg Gorsky, Natalia Merkulyeva & Pavel Musienko

  5. Ural Federal University, Yekaterinburg, Russia

    Allan V. Kalueff

  6. Department of Automatic Control and Systems Engineering, University of Sheffield, Sheffield, UK

    Ivan R. Minev

  7. Saint-Petersburg State Research Institute of Phthisiopulmonology, Ministry of Healthcare of the Russian Federation, Saint-Petersburg, Russia

    Pavel Musienko

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Contributions

I.R.M. and P.M. conceived of and initiated the project and wrote the manuscript. D.A., D.K., C.T., O.G., N.P., I.R.M. and P.M. designed and performed the experiments. D.A., D.K., V.L., C.T., S.M., N.M., A.V.K., I.R.M. and P.M. analysed the data and contributed to writing the manuscript. P.M. and I.R.M. supervised the study.

Corresponding authors

Correspondence to Ivan R. Minev or Pavel Musienko.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–18, captions for Supplementary Videos 1–3 and references.

Reporting Summary

Supplementary Video 1

Hybrid printing technology for personalized soft neuromuscular interfaces (NeuroPrint).

Supplementary Video 2

Facilitation of the spinal locomotor network by the NeuroPrint array.

Supplementary Video 3

Long-term biointegration of the NeuroPrint technology.

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Afanasenkau, D., Kalinina, D., Lyakhovetskii, V. et al. Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces. Nat Biomed Eng 4, 1010–1022 (2020). https://doi.org/10.1038/s41551-020-00615-7

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