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Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy

Nature Medicine volume 24, pages 1830–1836 (2018)Cite this article

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Abstract

Peripheral nerve injuries represent a significant problem in public health, constituting 2–5% of all trauma cases1. For severe nerve injuries, even advanced forms of clinical intervention often lead to incomplete and unsatisfactory motor and/or sensory function2. Numerous studies report the potential of pharmacological approaches (for example, growth factors, immunosuppressants) to accelerate and enhance nerve regeneration in rodent models3,4,5,6,7,8,9,10. Unfortunately, few have had a positive impact in clinical practice. Direct intraoperative electrical stimulation of injured nerve tissue proximal to the site of repair has been demonstrated to enhance and accelerate functional recovery11,12, suggesting a novel nonpharmacological, bioelectric form of therapy that could complement existing surgical approaches. A significant limitation of this technique is that existing protocols are constrained to intraoperative use and limited therapeutic benefits13. Herein we introduce (i) a platform for wireless, programmable electrical peripheral nerve stimulation, built with a collection of circuit elements and substrates that are entirely bioresorbable and biocompatible, and (ii) the first reported demonstration of enhanced neuroregeneration and functional recovery in rodent models as a result of multiple episodes of electrical stimulation of injured nervous tissue.

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Fig. 1: Bioresorbable, wireless electrical stimulator as an electronic neuroregenerative medical device.
Fig. 2: Surgical implantation, operation, and acute demonstration of a bioresorbable, wireless electrical stimulator for the sciatic nerve in a rodent model.
Fig. 3: Accelerated regeneration of sciatic nerves injured by transection, treated with the use of biodegradable wireless stimulators.
Fig. 4: Effects of chronic electrical stimulation on functional nerve recovery.

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Data availability

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

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Acknowledgements

S.-K.K. is supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2018R1C1B5043901). H.M.L. is supported by a grant from NRF funded by the Korean government (MEST) (2011-0028612). Z.X. acknowledges support from the National Natural Science Foundation of China (grant no.11402134). Y.H. acknowledges support from National Science Foundation (grant nos. 1400169, 1534120, and 1635443). J.A.R. acknowledges support from DARPA and from the Center for Bio-Integrated Electronics at Northwestern University. We thank S. J. Robinson (Beckman Institute, University of Illinois at Urbana-Champaign) and K. Doty (Department of Comparative Biosciences Histology Service Laboratory, University of Illinois at Urbana-Champaign) for histology staining and images that greatly improved the manuscript.

Author information

Author notes

  1. These authors contributed equally: Jahyun Koo, Matthew R. MacEwan, Seung-KyunKang.

Authors and Affiliations

  1. Center for Bio-Integrated Electronics, Northwestern University, Evanston, IL, USA

    Jahyun Koo, Seung Min Lee, Younggang Huang & John A. Rogers

  2. Department of Materials Science Engineering, Northwestern University, Evanston, IL, USA

    Jahyun Koo, Zhaoqian Xie, Seung Min Lee, Kaijing Luo, Bowen Ji, Anthony Banks, Younggang Huang & John A. Rogers

  3. Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, USA

    Matthew R. MacEwan, Manu Stephen, Paul Gamble, Ying Yan, Nathan Birenbaum, Jawad Khalifeh, Kelsey Bean, Michael Paskett, Zohny S. Zohny & Wilson Z. Ray

  4. Department of Biomedical Engineering, Washington University, St Louis, MO, USA

    Matthew R. MacEwan, Nathan Birenbaum & Wilson Z. Ray

  5. Department of Bio and Brain Engineering, Korea Advanced Institute of Science & Technology, Daejeon, Republic of Korea

    Seung-Kyun Kang

  6. KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science & Technology, Daejeon, Republic of Korea

    Seung-Kyun Kang

  7. Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Sang Min Won, Yu-Yu Chen, Jiho Shin, Sangjin Chung, Sung Bong Kim, Daniel V. Harburg, Ruoyao Zhang, Anthony Banks & John A. Rogers

  8. Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA

    Zhaoqian Xie, Kaijing Luo, Bowen Ji, Younggang Huang & John A. Rogers

  9. Department of Electronics Convergence Engineering, Kwangwoon University, Nowon-gu, Seoul, Republic of Korea

    Jeonghyun Kim

  10. Department of Materials Science and Engineering, Korea Advanced Institute of Science & Technology, Daejeon, Republic of Korea

    Hyuck Mo Lee

  11. Departments of Electrical Engineering, Computer Science, Chemistry and Biomedical Engineering, Northwestern University, Evanston, IL, USA

    John A. Rogers

  12. Simpson Querrey Institute for Nano/biotechnology, Northwestern University, Evanston, IL, USA

    John A. Rogers

  13. McCormick School of Engineering, Northwestern University, Evanston, IL, USA

    John A. Rogers

  14. Feinberg School of Medicine, Northwestern University, Evanston, IL, USA

    John A. Rogers

  15. Department of Neurological Surgery, Northwestern University, Evanston, IL, USA

    John A. Rogers

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Contributions

J. Koo, S.-K.K., S.M.W., Y.-Y.C., S.C., and J.A.R. designed and made the device. J. Koo, M.R.M., S.-K.K., S.B.K., S.M.L., J. Kim, R.Z., J.S., D.V.H., A.B., H.M.L., W.Z.R., and J.A.R. conceived the idea and performed the experiments and analysis. M.R.M., M.S., P.G., N.B., J. Khalifeh, Z.S.Z., K.B., M.P., Y.Y., and W.Z.R. performed the animal surgery, collected the nerve regeneration data, and analyzed the immunohistochemistry. Z.X., K.L., B.J., and Y.H. designed the antennas and ran the electromagnetic simulation. J. Koo, S.-K.K., M.R.M., Y.H., W.Z.R., and J.A.R. wrote the manuscript.

Corresponding authors

Correspondence to Wilson Z. Ray or John A. Rogers.

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Supplementary Text and Figures

Supplementary Figures 1–17

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Supplementary Video 1

Twitch response by stimulating sciatic nerve with bioresorbable stimulator

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Koo, J., MacEwan, M.R., Kang, SK. et al. Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy. Nat Med 24, 1830–1836 (2018). https://doi.org/10.1038/s41591-018-0196-2

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