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3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces

Nature Materials volume 22, pages 895–902 (2023)Cite this article

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Abstract

Owing to the unique combination of electrical conductivity and tissue-like mechanical properties, conducting polymer hydrogels have emerged as a promising candidate for bioelectronic interfacing with biological systems. However, despite the recent advances, the development of hydrogels with both excellent electrical and mechanical properties in physiological environments is still challenging. Here we report a bi-continuous conducting polymer hydrogel that simultaneously achieves high electrical conductivity (over 11 S cm−1), stretchability (over 400%) and fracture toughness (over 3,300 J m−2) in physiological environments and is readily applicable to advanced fabrication methods including 3D printing. Enabled by these properties, we further demonstrate multi-material 3D printing of monolithic all-hydrogel bioelectronic interfaces for long-term electrophysiological recording and stimulation of various organs in rat models.

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Fig. 1: Design and implementation of the BC-CPH.
Fig. 2: Electrical properties and stability of the BC-CPH.
Fig. 3: Applicability to diverse fabrication methods.
Fig. 4: All-hydrogel bioelectronic interfaces.
Fig. 5: In vivo electrophysiological recording and stimulation.
Fig. 6: In vivo biocompatibility.

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Data availability

All data supporting the findings of this study are available within the Article and its Supplementary Information. Additional raw data generated in this study are available from the corresponding authors on reasonable request.

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Acknowledgements

The authors thank the Koch Institute Swanson Biotechnology Centre, K. Cormier, and the Histology Core for the technical support and histological processing, and R. Bronson at Harvard Medical School for the histological evaluations. This work is supported by the National Institute of Health (1-R01-HL153857-01, X.Z.).

Author information

Author notes

  1. Tao Zhou

    Present address: Department of Engineering Science and Mechanics, Center for Neural Engineering, The Pennsylvania State University, University Park, PA, USA

  2. Hyunwoo Yuk

    Present address: SanaHeal, Inc, Cambridge, MA, USA

  3. These authors contributed equally: Tao Zhou, Hyunwoo Yuk.

Authors and Affiliations

  1. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Tao Zhou, Hyunwoo Yuk, Jingjing Wu, Heejung Roh & Xuanhe Zhao

  2. Flexible Electronics Innovation Institute, Jiangxi Key Laboratory of Flexible Electronics, Jiangxi Science and Technology Normal University, Nanchang, China

    Faqi Hu, Fajuan Tian, Jingkun Xu & Baoyang Lu

  3. Robotics Institute, School of Mechanical Engineering, State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai, China

    Zequn Shen & Guoying Gu

  4. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Xuanhe Zhao

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Contributions

H.Y., B.L. and X.Z. developed the concept and materials for the BC-CPH. H.Y. and T.Z. developed the materials and method for the printing-based fabrication and application of the all-hydrogel bioelectronic interfaces. B.L., H.Y., F.H., F.T. and J.X. conducted the electrical and mechanical characterizations of the BC-CPH. T.Z. and H.Y. conducted the electrical and mechanical characterizations of the all-hydrogel bioelectronic interfaces. T.Z., H.Y. and J.W. designed and conducted the in vivo animal studies. H.Y. and H.R. developed the materials and method for the printable bioadhesive. Z.S. and G.G. conducted the AFM phase imaging. H.Y. and X.Z. developed the multi-material printing platform. H.Y. prepared figures with inputs from all authors. H.Y., T.Z. and X.Z. wrote the manuscript with inputs from all authors.

Corresponding authors

Correspondence to Hyunwoo Yuk, Baoyang Lu or Xuanhe Zhao.

Ethics declarations

Competing interests

H.Y. and X.Z. have a financial interest in SanaHeal, a biotechnology company focused on the development of medical devices for surgical sealing and repair. The other authors declare no competing interests.

Peer review

Peer review information

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

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Extended data

Extended Data Fig. 1 Phase-separation of electrical and mechanical phases in the BC-CPH ink.

a-e, Macroscopic (left) and microscopic (right) images of hydrophilic polyurethane (PU) dissolved in ethanol-water mixed solvent with 90 v/v% (a), 70 v/v% (b), 50 v/v% (c), 30 v/v% (d), and 10 v/v% (e) ethanol concentrations. Green fluorescence corresponds to PU. f–j, Macroscopic (left) and microscopic (right) images of PEDOT:PSS dissolved in ethanol-water mixed solvent with 90 v/v% (f), 70 v/v% (g), 50 v/v% (h), 30 v/v% (i), and 10 v/v% (j) ethanol concentration. k, Macroscopic (left), confocal (middle), and bright-field (right) microscopic images of the BC-CPH ink in ethanol-water mixed solvent with 70 v/v% ethanol concentration. Green fluorescence corresponds to PU. FITC, fluorescein isothiocyanate. Each experiment was repeated independently 3 times.

Extended Data Fig. 2 Long-term stability of the BC-CPH in physiological environment.

a,b, Images (a) and weight (b) of the BC-CPH stored in PBS at 37 °C for 1, 7, 14, 28, 56, 84, and 180 days. c-e, Electrical conductivity (c), ultimate strain (d), and fracture toughness (e) of the BC-CPH stored in PBS at 37 °C. Values in b-e represent the mean and the standard deviation (n = 4; independent samples).

Extended Data Fig. 3 Wet adhesion chemistry of the bioadhesive and rapid sutureless integration to wet tissues.

a, Schematic illustrations for physical crosslinking between the bioadhesive and the target tissue surface by hydrogen bonds. b, Schematic illustrations for covalent crosslinking between the bioadhesive and the target tissue surface by amide bonds. c, Snapshots of sutureless bioadhesive integration of the all-hydrogel bioelectronic interface to a rat sciatic nerve. d, Interfacial toughness of the bioadhesive hydrogel adhered to various rat tissues. Note that tissues underwent cohesive failure for sciatic nerve and spinal cord. Values in d represent the mean and the standard deviation (n = 3; independent experiments).

Extended Data Fig. 4 Electrochemical stability of the all-hydrogel bioelectronic interface.

a–c, Impedance (blue symbols, left axis) and phase angle (red symbols, right axis) vs. frequency plots for one electrode channel in the all-hydrogel bioelectronic interface under varying tensile strain (a), tensile cycle (b), and storage time in PBS at 37 °C (c).

Extended Data Fig. 5 Rat spinal cord stimulation by the all-hydrogel bioelectronic interface.

a, Schematic illustration for rat spinal cord electrophysiological stimulation by the all-hydrogel bioelectronic interface. b, Images of the printed all-hydrogel bioelectronic interface for spinal cord in the overall view (left) and the magnified view of electrodes (right). Different materials are marked with colour overlays in the magnified view. c, Images of the implanted all-hydrogel bioelectronic interface on rat spinal cord. d, e, Images of rat forelimb before (left) and after (middle) electrophysiological stimulation of the spinal cord by the all-hydrogel bioelectronic interface with corresponding EMG recordings (right) on day 0 (d) and day 28 (e) post-implantation. The red-shaded regions in the EMG recordings indicate the stimulation pulses. f, g, Rat forelimb movement distance upon spinal cord stimulations by the all-hydrogel bioelectronic interface at varying stimulation currents on day 0 (f) and day 28 (g) post-implantation. h, Comparison of the rat forelimb movement distance on day 0, day 7, and day 28 post-implantation with stimulation current of 1.5 mA. In box plots (f-h), centre lines represent mean, box limits delineate standard error (SE), and whiskers reflect 5th and 95th percentile (n = 8; independent biological replicates). Statistical significance and p values are determined by two-sided unpaired t-test; *** p ≤ 0.001.

Supplementary information

Supplementary Information

Supplementary Discussions 1 and 2, Supplementary Table 1, Supplementary References and Supplementary Figures 1–33.

Reporting Summary

Supplementary Video 1

Multi-material 3D printing process of an all-hydrogel bioelectronic interface with the BC-CPH electrodes.

Supplementary Video 2

Sutureless bioadhesive integration of an all-hydrogel bioelectronic interface to a rat sciatic nerve in vivo.

Supplementary Video 3

On-demand detachment of an adhered all-hydrogel bioelectronic interface from a rat sciatic nerve in vivo.

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Zhou, T., Yuk, H., Hu, F. et al. 3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces. Nat. Mater. 22, 895–902 (2023). https://doi.org/10.1038/s41563-023-01569-2

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