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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30404 - Biomaterials (as related to medical implants, devices, sensors)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

—

Svazek periodika

119

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

e2115857119

Kód UT WoS článku

000775480500011

EID výsledku v databázi Scopus

2-s2.0-85126706736