An On-Demand Functionalizable Neural Electrode Interface for Precise Interrogation and Biofunctional Regulation

Neural electrodes capable of precise interrogation and biofunctional regulation—encompassing both long-term electrophysiological signal recording and tunable control of neuronal or pathological cell behavior via surface biofunctionalization—hold significant promise for advancing the diagnosis and treatment of neurological disorders. A critical challenge lies in mitigating the immune-mediated foreign body response, which often leads to glial scar formation that encapsulates implants like “cement,” severely compromising functionality. To address this, we develop a benzyloxycarbonyl (Cbz)-substituted poly(ornithine-alt-glycine) (OG Cbz ) interface, which inherently resists biofouling and immunogenic rejection without degrading electrical performance. Notably, substituting the Cbz group with various functional moieties not only maintains these excellent antifouling and biocompatibility properties but also imparts corresponding functionalities. As a proof-of-concept, replacing Cbz with the peptide sequence IKVAV and the antibody cetuximab successfully endows the interface with neuron-affinity and tumor cell proliferation inhibition, while retaining its inherent antifouling and anti-foreign-body reaction properties. During a six-month in vivo implantation period, the IKVAV-functionalized electrodes exhibit a significantly enhanced operational lifetime with improved electrophysiological signal fidelity. This work presents a reliable and versatile interfacial strategy for developing durable and multifunctional neural interfaces.