Iridium Oxide Nanoparticle–Protein Corona Neural Interfaces with Enhanced Electroactivity and Bioactivity Enable Electrically Manipulatable Physical and Chemical Neuronal Activation

Iridium oxide (IrO_x) is a promising implantable electrode material owing to its remarkable neural stimulation capacity. However, presently, IrO_x electrodes lack biocompatibility and bioactive interactions with nerve tissues. Application of polymeric surface coatings results in a weak physical adhesion at the organic/inorganic interface, which limits their wide-scale application. Herein, a smart iridium oxide-plasma protein (IrO_x-PP) electrode with enhanced electroactivity, electrochemical stability, cytocompatibility, and bioactivity that can provide controllable topographical, electrical, and chemical stimuli to enhance neuronal activity is proposed. In the inorganic/organic nanoparticle (NP)-protein corona structures, the soft NP-corona led to repeated burst-to-zero-to-burst PP release, while the hard NP-corona with an ordered atomic structure enhanced the electrochemical stability and bioactivity. The incorporated PP resulted in a higher current storage capacity, lower impedance, better cell growth, and significant neurite outgrowth compared with those obtained with pristine IrO_x. The application of electrical stimulation to IrO_x-PP enabled simultaneous neuromodulation, on-demand PP release, and cell uptake, with a 2-fold higher cell density and significant neurite outgrowth on IrO_x-PP than on pristine IrO_x. This bioactive inorganic-organic hybrid electrode with the combined features of physical properties and improved neuromodulation is expected to be a revolutionary platform for efficient and biocompatible neural implantation.