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. STATEMENT OF SIGNIFICANCE: To fabricate highly immunocompatible conductive
polymer-based
implantable electrodes with high performance and stability in vivo, we introduced the anti-inflammatory activity to PPy/Hep
electrodes by immobilizing
IL-4 via non-covalent surface modification. IL-4-immobilized PPy/Hep could significantly mitigate inflammatory responses and
scarring around implants by skewing macrophages to an anti-inflammatory phenotype. The IL-4-immobilized PPy/Hep
electrodes could successfully record in vivo electrocardiogram signals for up to 15 days with no substantial sensitivity loss, retaining their superior sensitivity compared to bare
gold and pristine PPy/Hep
electrodes. Our 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, such as neural
electrode arrays, biosensors, and cochlear
electrodes.