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Cited by 67Neuroscience and Neural EngineeringInflammasome and immune disordersNeuroinflammation and Neurodegeneration Mechanisms

Prevention of the foreign body response to implantable medical devices by inflammasome inhibition

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Barone, Damiano G., Carnicer-Lombarte, Alejandro, Tourlomousis, Panagiotis, Hamilton, Russell S., Prater, Malwina, Rutz, Alexandra L., Dimov, Ivan B., Malliaras, George G. +5 more·2022·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2115857119PMC PMC8944905
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Abstract

Significance: Implantable electronic medical devices (IEMDs) are used for some clinical applications, representing an exciting prospect for the transformative treatment of intractable conditions such Parkinson’s disease, deafness, and paralysis. The use of IEMDs is limited at the moment because, over time, a foreign body reaction (FBR) develops at the device–neural interface such that ultimately the IEMD fails and needs to be removed. Here, we show that macrophage nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity drives the FBR in a nerve injury model yet integration of an NLRP3 inhibitor into the device prevents FBR while allowing full healing of damaged neural tissue to occur.

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Crossref · 10.1073/pnas.2115857119

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  • The chronic stage is predominantly mediated by macrophages and foreign body giant cells, which are generated from the fused macrophages.

    “This stage is predominantly mediated by macrophages and foreign body giant cells, which are generated from the fused macrophages.”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [207]

    The Discussion names macrophages and foreign body giant cells among cells recruited during the foreign body response, and says macrophages activate fibroblasts that mediate fibrosis. It does not say that macrophages and giant cells predominantly mediate the chronic stage or that giant cells form by macrophage fusion. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Macrophages, by crosstalk with the myofibroblasts, regulate the degradation of the implanted material and also coordinate the formation of granulation tissue, which is the precursor for fibrous capsule development.

    “Macrophages, by crosstalk with the myofibroblasts, regulate the degradation of the implanted material and also coordinate the formation of granulation tissue, which is the precursor for fibrous capsule development [207].”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [207]

    The Discussion says macrophages activate acta2-expressing fibroblasts that mediate fibrosis. The paper also says macrophages try to degrade implanted material and are thought to coordinate the fibroblast response that forms a capsule. It does not describe macrophages coordinating granulation-tissue formation or identify granulation tissue as a precursor to the capsule. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Lymphocytes also participate, but their role still remains poorly understood.

    “In addition, lymphocytes also participate, but their role still remains poorly understood.”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [207]

    The Discussion says the role of dendritic cells in the foreign body response remains poorly understood, but does not make that statement about lymphocytes. The Methods list B cells, T cells and natural killer cells among cell types distinguishable by the RNA-seq analysis; they do not establish the claimed participation or characterize their role. Searches for lymphocytes and their role found no passage that settles the claim. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cites

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Authors
Barone, D. G., Carnicer-Lombarte, A., Tourlomousis, P., Hamilton, R. S., Prater, M., Rutz, A. L., Dimov, I. B., Malliaras, G. G., Lacour, S. P., Robertson, A. A. B., Franze, K., Fawcett, J. W., & Bryant, C. E.
Affiliations
  • University of Cambridge (GB)
  • John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, United Kingdom
  • Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, 1202 Geneva, Switzerland
  • The University of Queensland (AU)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Czech Academy of Sciences (CZ)
Corresponding author
  • Fawcett, James W.
  • Bryant, Clare E.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2022-03-17
Volume
119
Issue
12
Pages
e2115857119-e2115857119
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2115857119
PMC
PMC8944905
OpenAlex
W4221014594
Cited by
67
References
10
Citations by year
2026: 10 · 2025: 17 · 2024: 14 · 2023: 23 · 2022: 3
FWCI
6.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • Apollo (cc-by)
Funders
  • Alexander von Humboldt-Stiftung
  • Fondation Bertarelli
  • Wellcome Trust (Z/17/Z, 772426, 085686/Z/08/A, 108045/Z/15/Z, 208363/Z/17/Z, 108045, /Z/15/Z, 208363, 109511/Z/15/Z, 109511)
  • National Institute for Health and Care Research (CL-2019-14-004)
  • European Commission (772426, HORIZON2020, 797506)
  • University of Queensland (QLD 4072)
  • Akademie Věd České Republiky
  • Directorate for Biological Sciences
  • Medical Research Council (208363/Z/17/Z, MC_UU_00014/5, RG70550)
  • Engineering and Physical Sciences Research Council (EP/L015978/1)
  • Biotechnology and Biological Sciences Research Council (BB/N006402/1)
  • H2020 European Research Council (772426)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
foreign body reaction, NLRP3 inflammasome, inflammasome inhibition, macrophages, neuroprosthetics
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Foreign Bodies, Humans, Macrophages, Prostheses and Implants, Inflammasomes

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