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Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions.

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Peer-reviewed

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Abstract

Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

Description

Acknowledgements: The authors would like to acknowledge Dr. Rachana Acharya and the Mechanical Testing Laboratory of the Department of Materials Science & Metallurgy of the University of Cambridge for their support in the tensile test experiments. A.C.L. acknowledges support from the University of Cambridge for a Borysiewicz Interdisciplinary Fellowship and the Wellcome Trust for a Junior Interdisciplinary Fellowship. A.J.B. acknowledges support from his Cross-disciplinary Fellowship (LT000034/2020-C) from the Human Frontier Science Program (HFSP) Organization. A.G. acknowledges funding support from the Royal Commission for the Exhibition of 1851. J. G. acknowledges the support from the German Research Foundation (Deutsche Forschungsgemeinschaft DFG via Research Fellowships Gz. GU 2073/1-1). S.V.B. acknowledges support from the W.D. Armstrong Studentship. This work was funded by the EPSRC (EP/T004908/1, IAA Follow-on Fund RG90413), MRC CiC (RG84584), the ECH2020 FUTURE & EMERGING TECHNOLOGIES (FET) projects BrainCom (732032) and MITICS (964677), and by the University of Cambridge Centre for Integrative Neuroscience Discovery (CIND) Early Career Researcher Funding.


Funder: Royal Commission for the Exhibition of 1851; doi: https://doi.org/10.13039/501100000700

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Journal Title

Nat Commun

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Journal ISSN

2041-1723
2041-1723

Volume Title

15

Publisher

Springer Nature

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Except where otherwised noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Sponsorship
EPSRC (EP/T004908/1)