Implantable polypyrrole bioelectrodes inducing anti-inflammatory macrophage polarization for long-term in vivo signal recording

Bioelectrodes are critical components of implantable electronic devices that enable precise electrical signal transmission in close contact with living tissues. However, their in vivo performance is often compromised by inflammatory tissue reactions mainly induced by macrophages. Hence, we aimed to develop implantable bioelectrodes with high performance and high biocompatibility by actively modulating the inflammatory response of macrophages. Consequently, we fabricated heparin-doped polypyrrole electrodes (PPy/Hep) and immobilized anti-inflammatory cytokines (interleukin-4 [IL-4]) via non-covalent interactions. IL-4 immobilization did not alter the electrochemical performance of the original PPy/Hep electrodes. In vitro primary macrophage culture revealed that IL-4-immobilized PPy/Hep electrodes induced anti-inflammatory polarization of macrophages, similar to the soluble IL-4 control. In vivo subcutaneous implantation indicated that IL-4 immobilization on PPy/Hep promoted the anti-inflammatory polarization of host macrophages and significantly mitigated scarring around the implanted electrodes. In addition, high-sensitivity electrocardiogram signals were recorded from the implanted IL-4-immobilized PPy/Hep electrodes and compared to bare gold and PPy/Hep electrodes, which were maintained for up to 15 days post-implantation. This simple and effective surface modification strategy for developing immune-compatible bioelectrodes will facilitate the development of various electronic medical devices that require high sensitivities and long-term stabilities.