Prevention of the foreign body response to implantable medical devices by inflammasome inhibition
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F22%3A00566570" target="_blank" >RIV/68378041:_____/22:00566570 - isvavai.cz</a>
Result on the web
<a href="https://www.pnas.org/doi/full/10.1073/pnas.2115857119" target="_blank" >https://www.pnas.org/doi/full/10.1073/pnas.2115857119</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1073/pnas.2115857119" target="_blank" >10.1073/pnas.2115857119</a>
Alternative languages
Result language
angličtina
Original language name
Prevention of the foreign body response to implantable medical devices by inflammasome inhibition
Original language description
Fibrotic scarring secondary to the foreign body reaction (FBR) generates a physical barrier obstructing the functional interaction of implantable medical devices with the host tissue. The mechanistic basis of the FBR is poorly understood, restricting the current therapeutic options to prevent it. Here, we show that in a peripheral nerve injury-implant model (NI) the FBR has a dysregulated innate immune profile recruiting MI-like activated macrophages, immature macrophages, activated dendritic cells, and immature dendritic cells compared with nerve injury alone, which recruits predominantly M2-like macrophages. The gene signature of the FBR shows increased myofibroblast activity, explaining why collagen and scarring are present, but also up-regulation of inflammasome constituents. Local delivery of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome inhibitor MCC950, through its incorporation into the silicone coating of implants, reduced the inflammation and fibrosis associated with both NI and subcutaneous implantable devices. In the NI model, MCC950 did not affect neuronal repair. Inhibition of the NLRP3 inflammasome may, therefore, be a promising therapeutic approach to prevent the FBR, hence prolonging the functional lifespan of implantable medical devices and neural implants.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30404 - Biomaterials (as related to medical implants, devices, sensors)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424
e-ISSN
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Volume of the periodical
119
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
e2115857119
UT code for WoS article
000775480500011
EID of the result in the Scopus database
2-s2.0-85126706736