Electroactive nanostructured polypyrrole coatings with on-demand drug release for immunomodulation of neural electrode interfaces.

Neural electrodes are central to a wide range of neuroprosthetic and neuromodulation technologies. However, persistent macrophage-driven inflammation often leads to fibrotic encapsulation and elevated electrical impedance, severely limiting stimulation efficiency and device longevity. Here, we reported an electroactive, electrically controlled drug-releasing neural electrode coating based on nanostructured polypyrrole (NPPy), enabling on-demand and sustained immunomodulation at neural interfaces. The nanostructured coating exhibited a high drug-loading capacity and released dexamethasone in a time-dependent manner under electrical stimulation. Electrically triggered drug release effectively suppressed lipopolysaccharide-induced macrophage M1 polarization, significantly reducing pro-inflammatory cytokine secretion, nitric oxide production, and inflammatory gene expression. Using cochlear implants as a representative peripheral neural electrode system, a transwell co-culture model demonstrated that macrophage-mediated inflammatory injury severely impairs spiral ganglion neuron survival and neurite extension, whereas electrically released dexamethasone markedly preserved neuronal viability and promoted neurite outgrowth. By coupling electrical stimulation with on-demand immunomodulatory drug delivery, this work established a generalizable electroactive coating strategy for dynamic regulation of neural electrode interfaces, offering a promising route to enhance the long-term stability and functional performance of implantable neural electrodes.