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

Published version
Repository URI
https://www.repository.cam.ac.uk/handle/1810/336153
Repository DOI
https://doi.org/10.17863/CAM.83578
Files
Published version (1.58 MB)
Type
Article
Change log
Authors
Carnicer-Lombarte, Alejandro 
Tourlomousis, Panagiotis 
Hamilton, Russell S  ORCID logo  https://orcid.org/0000-0002-0598-3793
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Abstract

SignificanceImplantable 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.

Description
Keywords
MCC950, NLRP3 inflammasome, foreign body reaction, neural interfaces, Foreign Bodies, Humans, Inflammasomes, Macrophages, NLR Family, Pyrin Domain-Containing 3 Protein, Prostheses and Implants
Journal Title
Proc Natl Acad Sci U S A
Conference Name
Journal ISSN
0027-8424
1091-6490
Volume Title
119
Publisher
Proceedings of the National Academy of Sciences
Publisher DOI
https://doi.org/10.1073/pnas.2115857119
Rights
Attribution 4.0 International Repository logo
Sponsorship
Wellcome Trust (085686/Z/08/A)
Engineering and Physical Sciences Research Council (EP/L015978/1)
Wellcome Trust (108045/Z/15/Z)
Biotechnology and Biological Sciences Research Council (BB/N006402/1)
Wellcome Trust (208363/Z/17/Z)
European Research Council (772426)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (797506)
MRC (MC_UU_00014/5)
Part of the RNA-Seq work was performed with the Genomics and Transcriptomics Core, which is funded by the UK Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_00014/5) and a Wellcome Trust Major Award (208363/Z/17/Z), and guidance from Marcella Ma, whom the authors wish to thank. CEB was supported by a Wellcome Trust Investigator award (108045/Z/15/Z). This work was also supported by the UK Wellcome Trust (Translational Medicine and Therapeutics PhD Programme Fellowship 109511/Z/15/Z to DGB), the UK Health Education England and the National Institute for Health Research (HEE/ NIHR ICA Program Clinical Lectureship CL-2019-14-004 to DGB), the UK Medical Research Council (MRC) and the Sackler Foundation (doctoral training grant RG70550 to ACL), the Engineering and Physical Sciences Research Council (EPSRC) Cambridge NanoDTC (EP/L015978/1), the Centre for Trophoblast Research (MP and RSH), the Whitaker International Scholars Program (ALR), the European Commission’s Horizon 2020 (Marie Sklodowska-Curie Fellowship 797506 to ALR), the Bertarelli Foundation (SPL), the European Research Council (Consolidator Award 772426 to KF), the UK Biotechnology and Biological Sciences Research Council (Research Grant BB/N006402/1 to KF), and the Alexander von Humboldt Foundation (Humboldt Professorship to KF).
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