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Injectable tissue prosthesis for instantaneous closed-loop rehabilitation - Nature


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Nature volume 623pages 58–65 (2023)

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Abstract

To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues1,2. Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces,,5. Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request. Source data are provided with this paper.

Code availability

All customized MATLAB code used for in vivo demonstration in this work is available in a repository at https://github.com/chwchw2/C-RAR-demo.git.

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Acknowledgements

This study was financially supported by the National Research Foundation of Korea grant funded by the Korean government (MSIT) (nos. RS-2023-00208262 (M.S.) and 2020R1C1C1005567 (D.S.)). This research was also supported by the Institute for Basic Science (no. IBS-R015-D1). This research was also supported by the Korean Fund for Regenerative Medicine grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (23B0102L1).

Author information

Author notes

  1. These authors contributed equally: Subin Jin, Heewon Choi

Authors and Affiliations

  1. Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Republic of Korea

    Subin Jin & Mikyung Shin

  2. Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea

    Subin Jin, Heewon Choi, Duhwan Seong, Donghee Son & Mikyung Shin

  3. Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, Republic of Korea

    Heewon Choi, Duhwan Seong & Donghee Son

  4. Department of Molecular Cell Biology, Single Cell Network Research Center, School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea

    Chang-Lim You & Jong-Sun Kang

  5. School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea

    Seunghyok Rho & Won Bo Lee

  6. Department of Superintelligence Engineering, Sungkyunkwan University, Suwon, Republic of Korea

    Donghee Son

  7. Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University, Suwon, Republic of Korea

    Mikyung Shin

Authors

  1. Subin Jin

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  2. Heewon Choi

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  3. Duhwan Seong

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  4. Chang-Lim You

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  5. Jong-Sun Kang

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  6. Seunghyok Rho

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  7. Won Bo Lee

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  8. Donghee Son

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  9. Mikyung Shin

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Contributions

S.J. conducted experiments for synthesis of the polymers and their characterization. S.J. and H.C. performed all in vivo experiments. D.S. and H.C. conducted electrochemical characterization of the materials. C.-L.Y. and J.-S.K. performed histological analysis and discussed the results. S.R. and W.B.L. conducted computational MD simulations. S.J., H.C., D.S. and M.S. wrote the first draft of the manuscript. M.S. and D.S. conceived and supervised the project. All authors discussed and commented on the data.

Corresponding authors

Correspondence to Donghee Son or Mikyung Shin.

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The authors declare no competing interests.

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Peer review information

Nature thanks Milica Radisic and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data figures and tables

Extended Data Fig. 1 The RAR system based on muscle IT-IC interfacing without the sciatic nerve stimulation.

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a, Schematics of the RAR system based on the TA muscle-tissue conduction by the IT-IC hydrogel without using the peripheral nerve interface. The TA muscle EMG signal evoked by voluntary walking is recorded by the EMG electrode. When specific TA muscle EMG signals are detected, the robotic assistance is activated. The rat’s leg movement is then fully supported by the robotic assistance. b, Recorded EMG signals and waveforms (inset) of untreated rats using the RAR system. c, Photographs of unsynchronized robot activation and the corresponding abnormal steps. d, Recorded EMG signals and waveforms (inset) of IT-IC hydrogel-treated rats using RAR. e, Photographs of robotic assistance and the corresponding normal steps.

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Jin, S., Choi, H., Seong, D. et al. Injectable tissue prosthesis for instantaneous closed-loop rehabilitation. Nature 623, 58–65 (2023). https://doi.org/10.1038/s41586-023-06628-x

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