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

0566570 - ÚEM 2023 RIV US eng J - Journal Article
Barone, D.G. - Carnicer-Lombarte, A. - Tourlomousis, P. - Hamillton, R.S. - Prater, M. - Rutz, A.L. - Dimov, I.B. - Malliaras, G.G. - Lacour, S.P. - Robertson, A.A.B. - Franze, K. - Fawcett, James - Bryant, C.E.
Prevention of the foreign body response to implantable medical devices by inflammasome inhibition.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 119, č. 2 (2022), č. článku e2115857119. ISSN 0027-8424. E-ISSN 1091-6490
Institutional support: RVO:68378041
Keywords : foreign body reaction * NLRP3 inflammasome * neural interfaces * MCC950
OECD category: Biomaterials (as related to medical implants, devices, sensors)
Impact factor: 11.1, year: 2022
Method of publishing: Open access
https://www.pnas.org/doi/full/10.1073/pnas.2115857119

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.
Permanent Link: https://hdl.handle.net/11104/0340956