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.

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

Centre for Reconstructive Neuroscience Institute for Experimental Medicine Czech Academy of Sciences 142 20 Prague 4 Czech Republic

Centre for Trophoblast Research University of Cambridge Cambridge CB2 3EG United Kingdom

Department of Genetics University of Cambridge Cambridge CB2 3EH United Kingdom

Department of Physiology Development and Neuroscience University of Cambridge Cambridge CB2 3DY United Kingdom

Department of Veterinary Medicine University of Cambridge Cambridge CB3 0ES United Kingdom

Division of Medicine University of Cambridge Cambridge CB2 0PY United Kingdom

Division of Neurosurgery Department of Clinical Neurosciences University of Cambridge Cambridge CB2 0PY United Kingdom

Electrical Engineering Division Department of Engineering University of Cambridge Cambridge CB3 0FA United Kingdom

Institute of Medical Physics and Microtissue Engineering Friedrich Alexander University Erlangen Nuremberg 91052 Erlangen Germany

John van Geest Centre for Brain Repair Department of Clinical Neurosciences University of Cambridge Cambridge CB2 0PY United Kingdom

Max Planck Zentrum für Physik und Medizin 91054 Erlangen Germany

School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD 4072 Australia

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