Implantable conductive polymer bioelectrode with enzymatic antioxidant activity for enhanced tissue responses and in vivo performance

Abstract

Implantable bioelectrodes enable precise diagnosis and treatment through direct transmission of electrical signals in the living tissues. However, a fundamental challenge arises as implanted bioelectrodes frequently lose performance due to adverse tissue reactions, primarily induced by high oxidative stress and subsequent inflammatory activation of macrophages. In this study, we investigated a novel strategy to address this challenge in implantable bioelectrodes by introducing reactive oxygen species (ROS)-scavenging capabilities to the bioelectrodes. Specifically, a polypyrrole (PPy) electrode doped with hemin-conjugated heparin (HepH) was fabricated to impart robust enzyme-like antioxidant properties. The HepH-doped PPy electrodes exhibited a catalase-mimicking activity, as evidenced by hydrogen peroxide scavenging and oxygen gas generation in the presence of hydrogen peroxide. In vitro primary macrophage culture and in vivo subcutaneous implantation studies revealed that HepH-incorporated PPy electrodes reduced intracellular ROS levels and directed macrophage polarization toward an anti-inflammatory phenotype, mitigating collagenous scar tissue formation around the implanted electrodes. Finally, real-time electrocardiogram monitoring for 20 days demonstrated the extended in vivo signal sensitivity of the HepH-doped PPy electrodes as reliable implantable bioelectrodes.