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An injectable conductive hydrogel for closed-loop and robot-assisted rehabilitation via stretchable patch-type electrodes

Nature Protocols volume 21, pages 238–262 (2026)Cite this article

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Abstract

Conventional therapies for severe musculoskeletal and neurological injuries require lengthy recovery periods, which may result in residual disabilities. As an innovative rehabilitation approach, the combination of soft conducting hydrogels as an injectable tissue prosthesis with self-healing, stretchable bioelectronic devices offers a promising solution to expedite tissue repair and enhance functional restoration. This class of tissue prostheses can help address the critical limitations of traditional materials and devices by providing a minimally invasive approach to filling tissue defects and reconstructing the electrophysiological environment. The integration of an injectable tissue prosthesis with exoskeleton robotics in closed-loop systems enables tailored rehabilitation interventions that optimize motor function efficiency. Here we provide the step-by-step instructions for the development and characterization of injectable tissue-interfacing conductive hydrogels and soft self-healing, stretchable bioelectronic devices. We also describe how to establish a fully integrated closed-loop rehabilitation system and show its efficacy in a rat model of volumetric muscle loss. Using this approach, we have achieved accelerated tissue regeneration and improved myofiber regeneration in rats, underscoring the potential of this approach to improve rehabilitation strategies for severe injuries. The protocol is suitable for users with experience in biomaterials, devices and animal handling and requires 30 d to complete.

Key points

  • This protocol covers the preparation of injectable and conductive hyaluronic acid hydrogels, fabrication of soft self-healing and stretchable electronic devices and their in vivo applications for closed-loop rehabilitation at the early stage of muscle damage.

  • This protocol provides a detailed strategy for a closed-loop robot-assisted system with precisely controlled stimulation feedback through electromyogram, enabling locomotion recovery in a rat model of volumetric muscle loss.

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Fig. 1: Overview of instantaneous rehabilitation platform with IT-IC hydrogels as injectable tissue prostheses, SH-SB devices and their fully integrated system by closed-loop robotic control.
Fig. 2: Schematic illustrations for formation and preparation of IT-IC hydrogels.
Fig. 3: Schematic illustrations for the fabrication of SH-SB devices.
Fig. 4: Photographs and schematic illustration of C-RAR system.
Fig. 5: IT-IC hydrogels for tissue-to-tissue conduction and effective myofiber regeneration.
Fig. 6: The SH-SB patch for afferent neural signal recording and neuromodulation in PNs.
Fig. 7: The integrated platforms of IT-IC hydrogel and SH-SB patches for closed-loop rehabilitation system.

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Data availability

All pertinent experimental and characterization data discussed in this protocol are available in the supporting primary research articles12,28 and within this study.

Code availability

The code used in this protocol is available in a repository via GitHub at https://github.com/chwchw2/closed-loop-rehabilitation-protocol-code.

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Acknowledgements

This study was financially supported by the National Research Foundation of Korea grant funded by the Korean government (MSIT) (grant nos. RS-2023-00208262 to M.S. and 2020R1C1C1005567 to D.S.). This research was also supported by the Institute for Basic Science (grant 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 and the Ministry of Health and Welfare) (grant no. 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, Donghee Son & Mikyung Shin

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

    Heewon Choi & Donghee Son

  4. Department of Artificial Intelligence System Engineering, Sungkyunkwan University, Suwon, Republic of Korea

    Donghee Son

  5. Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea

    Mikyung Shin

Authors
  1. Subin Jin
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  2. Heewon Choi
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  3. Donghee Son
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Contributions

S.J. and H.C. contributed equally to the development and validation of the protocol. S.J. fabricated and characterized IT-IC hydrogels. H.C. fabricated and characterized the SHP, AuNM–AgF–SHP composites and SH-SB devices. S.J. and H.C. conducted in vivo experiments. D.S. and M.S. supervised the project and provided critical revisions. All authors wrote the main manuscript.

Corresponding authors

Correspondence to Donghee Son or Mikyung Shin.

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The authors declare no competing interests.

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Nature Protocols thanks the anonymous reviewers for their contribution to the peer review of this work.

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Key references

Jin, S. et al. Nature 623, 58–65 (2023): https://doi.org/10.1038/s41586-023-06628-x

Song, K.-I. et al. Nat. Commun. 11, 4195 (2020): https://doi.org/10.1038/s41467-020-18025-3

Supplementary information

Supplementary Information

Supplementary Figs. 1–13 and references 1 and 2.

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Jin, S., Choi, H., Son, D. et al. An injectable conductive hydrogel for closed-loop and robot-assisted rehabilitation via stretchable patch-type electrodes. Nat Protoc 21, 238–262 (2026). https://doi.org/10.1038/s41596-025-01184-2

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