The DOI matches its Crossref record; 80 of the 82 references it cites were found in a registry or an index.
Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes
Open accessAbstract
Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes in the electrical properties of actively used intra-neural electrodes, highlighting functional stability of polyimide-based implants over more than six months. These results are essential for refining and validating these implants and open a realistic pathway for long-term clinical applications in humans.
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In the citing paper
“A further study evaluated the results of SELINE insertion into the sciatic nerve of rats for 6 months [181]. Inflammatory response with swollen fibers was observed in the early phase after implantation, but it gradually resulted in capsule formation around the place of implantation, and all of the electrodes were functional at the end of the study.”
From Interfaces with the peripheral nervous system for the control of a neuroprosthetic limb: a review (2020) · cites this paper as [181]
In the citing paper
“The selectivity, longevity, and long-term stability are absolutely an integral part for the establishment of long-lasting and functional sensory feedback for an amputee (Warren et al., 2016; Wurth et al., 2017).”
From Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review. (2017) · cites this paper as Wurth et al., 2017
In the citing paper
“The most recent study of Wurth et al. (2017) has demonstrated the selectivity, stability, longevity, and biocompatibility of intra-neural type interfaces.”
From Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review. (2017) · cites this paper as Wurth et al. (2017)
Citations
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Self-citationRestoring natural sensory feedback in real-time bidirectional hand prostheses
Raspopovic, S., Capogrosso, M., Petrini, F. M., Bonizzato, M., Rigosa, J., Di Pino, G., Carpaneto, J., Controzzi, M., Boretius, T., Fernandez, E., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3006820 · Cited by 1,001
Self-citationMacrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves
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Cited by
Sorted by citations
Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics
Carnicer-Lombarte, A., Chen, S.-T., Malliaras, G. G., & Barone, D. G. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.622524 · Cited by 454
“Self-deploying anchors can also be incorporated into intraneural designs, minimizing movement and the associated trauma following implantation, as seen with self-opening neural interface (SELINE) devices (Cutrone et al., 2015), and generating minimal FBR (Wurth et al., 2017).”
BackgroundSensory feedback for limb prostheses in amputees
Raspopovic, S., Valle, G., & Petrini, F. M. (2021) · Nature Materials · doi:10.1038/s41563-021-00966-9 · Cited by 308
Toward higher-performance bionic limbs for wider clinical use
Farina, D., Vujaklija, I., Brånemark, R., Bull, A. M. J., Dietl, H., Graimann, B., Hargrove, L. J., Hoffmann, K.-P., Huang, H., Ingvarsson, T., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00732-x · Cited by 263
Self-citationRestoration of sensory information via bionic hands
Bensmaı̈a, S. J., Tyler, D. J., & Micera, S. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00630-8 · Cited by 264
Self-citationRecent Advances in Materials, Devices, and Systems for Neural Interfaces
Won, S. M., Song, E., Zhao, J., Li, J., Rivnay, J., & Rogers, J. A. (2018) · Advanced Materials · doi:10.1002/adma.201800534 · Cited by 206
Metadata
- Authors
- Wurth, S., Capogrosso, M., Raspopovic, S., Gandar, J., Federici, G., Kinany, N., Cutrone, A., Piersigilli, A., Pavlova, N., Guiet, R., Taverni, G., Rigosa, J., Shkorbatova, P., Navarro, X., Barraud, Q., Courtine, G., & Micera, S.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Scuola Superiore Sant'Anna (IT)
- University of Bern (CH)
- Pavlov Institute of Physiology of the Russian Academy of Sciences (RU)
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Micera, S.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 122
- Pages
- 114-129
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2578816048
- Cited by
- 176
- References
- 82
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 20 · 2023: 18 · 2022: 20 · 2021: 29 · 2020: 16 · 2019: 19 · 2018: 15 · 2017: 7
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 294 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- CINECA IRIS Institutional Research Information System (Sant'Anna School of Advanced Studies) (submittedVersion)
- Funders
- Wyss Center for Bio and Neuroengineering
- European Commission (FP7-611687)
- European Research Council (ERC 261247)
- École Polytechnique Fédérale de Lausanne
- International Foundation for Research in Paraplegia
- Fondation Bertarelli
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (205321_170032, 315230_149902)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Physical Sciences › Engineering › Biomedical Engineering › Muscle activation and electromyography studies
- Keywords
- polyimide electrodes, peripheral nerve stimulation, sciatic nerve, long-term biocompatibility, foreign body reaction, fibrotic capsule, electrical impedance, stimulation threshold, Wallerian degeneration, macrophage infiltration, multinucleated giant cells, nerve regeneration, implant encapsulation
- MeSH terms
- Animals, Biocompatible Materials, Electric Stimulation, Equipment Design, Female, Longitudinal Studies, Microelectrodes, Rats, Inbred Lew, Resins, Synthetic, Sciatic Nerve, Treatment Outcome, Equipment Failure Analysis, Rats, Implantable Neurostimulators
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