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Chronic electrical stimulation of peripheral nerves via deep-red light transduced by an implanted organic photocapacitor

Abstract

Implantable devices for the wireless modulation of neural tissue need to be designed for reliability, safety and reduced invasiveness. Here we report chronic electrical stimulation of the sciatic nerve in rats by an implanted organic electrolytic photocapacitor that transduces deep-red light into electrical signals. The photocapacitor relies on commercially available semiconducting non-toxic pigments and is integrated in a conformable 0.1-mm3 thin-film cuff. In freely moving rats, fixation of the cuff around the sciatic nerve, 10 mm below the surface of the skin, allowed stimulation (via 50–1,000-μs pulses of deep-red light at wavelengths of 638 nm or 660 nm) of the nerve for over 100 days. The robustness, biocompatibility, low volume and high-performance characteristics of organic electrolytic photocapacitors may facilitate the wireless chronic stimulation of peripheral nerves.

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Fig. 1: OEPCs wirelessly stimulate the sciatic nerve in vivo.
Fig. 2: Photostimulated OEPC devices deliver rapid localized electrolytic pulses.
Fig. 3: Acute sciatic nerve photostimulation is precisely controlled by varying OEPC device size, light intensity and stimulation pulse length.
Fig. 4: Self-fixating OEPCs are mechanically robust to intra-operative placement and chronic in vivo implantation.
Fig. 5: OEPCs permit chronic, non-invasive in vivo sciatic nerve stimulation.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. All data generated in this study, including source data and the data used to make the figures, are available from figshare with the identifier https://doi.org/10.6084/m9.figshare.15015099. Source data are provided with this paper.

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Acknowledgements

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 949191, E.D.G.). We acknowledge financial support from the Knut and Alice Wallenberg Foundation within the framework of the Wallenberg Centre for Molecular Medicine at Linköping University (E.D.G.), the Swedish Research Council (Vetenskapsrådet, 2018-04505, E.D.G.) and the Swedish Foundation for Strategic Research (E.D.G. and M.B.). This work was also supported by Columbia University, School of Engineering and Applied Science, as well as Columbia University Medical Center, Department of Neurology and Institute for Genomic Medicine. We acknowledge CzechNanoLab Research Infrastructure, supported by MEYS CR (LM2018110). This work has been supported by the Croatian Science Foundation under project UIP-2019-04-1753 (V.Đ.). V.Đ. acknowledges the support of project CeNIKS, co-financed by the Croatian Government and the European Union through the European Regional Development Fund – Competitiveness and Cohesion Operational Programme (grant no. KK.01.1.1.02.0013), and the QuantiXLie Center of Excellence, a project co-financed by the Croatian Government and European Union through the European Regional Development Fund – the Competitiveness and Cohesion Operational Programme (grant no. KK.01.1.1.01.0004). Financial support by the Center of Excellence for Advanced Materials and Sensors, Croatia, is gratefully acknowledged. We also thank H. Khodagholy for the design and fabrication of the horizontal ladder apparatus.

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Contributions

M.S.E., M.J. and L.M. carried out the photoelectrochemical characterizations. M.S.E., M.J., V.Đ., D.K. and J.N.G. performed acute experiments and analysed data. L.M. fabricated the devices for the acute experiments. M.J. fabricated the devices for the chronic experiments. V.Đ. wrote programs for data acquisition, processing and MC modelling. I.S. performed calculations with finite-element models. Z.Z. designed and developed the electrophysiological acquisition hardware. J.J.F., D.K. and J.N.G. performed the rodent surgeries. Chronic data were collected and analysed by M.J., J.J.F., Z.Z., J.N.G. and E.D.G. J.J.F. and M.S.E. performed the rat behavioural testing. J.J.F. conducted immunohistochemistry experiments. The project was led and supervised by M.B., D.K., V.Đ., J.N.G. and E.D.G. The manuscript was written with input from all co-authors.

Corresponding authors

Correspondence to Vedran Đerek, Jennifer N. Gelinas or Eric Daniel Głowacki.

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The authors declare no competing interests.

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Peer review information Nature Biomedical Engineering thanks Gregoire Courtine, John Ho and Bozhi Tian for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary appendix, figures, table and video captions.

Reporting Summary

Video 1

Initial acute photostimulation experiments, as described in Fig. 3.

Video 2

Leg-muscle twitches on the application of 1-ms light pulses at a frequency of 0.33 Hz, 14 days following implantation of the device.

Video 3

When the implant site is surgically opened and photostimulation is performed, clear muscle twitches are once again visible.

Video 4

Horizontal ladder test for rats with the implanted device versus control rats.

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Silverå Ejneby, M., Jakešová, M., Ferrero, J.J. et al. Chronic electrical stimulation of peripheral nerves via deep-red light transduced by an implanted organic photocapacitor. Nat. Biomed. Eng 6, 741–753 (2022). https://doi.org/10.1038/s41551-021-00817-7

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