A MCC950 analogue inflammasome inhibitor reduces the foreign body reaction against neural implants

Abstract

Devices implanted in the body provoke a foreign body reaction (FBR) that results in tissue encapsulation of the device and hampers its functionality over time. This FBR is particularly relevant regarding long-term implanted neural electrodes. Inflammasome inhibitors may represent a novel treatment to reduce the initial macrophage activation, and thus reduce the FBR and improve the outcome of implanted devices. We have synthetized an inflammasome inhibitor, named TDV19, and tested its capability to reduce macrophage activation in vitro, in comparison with the standard inhibitor MCC950. Then, polyimide thin-film devices were longitudinally implanted in the rat sciatic nerve and tested for 2 months to evaluate the intraneural FBR. Systemic administration of TDV19 and of MCC950 significantly reduced macrophage infiltration in the nerve and thickness of the fibrotic capsule around the device. Thus, systemic administration of inflammasome inhibitors appears as a useful treatment to improve the fate of chronically implanted neural electrodes.