Multifunctional Electrode/Neural Integration Interface Enabling Chronic High‐Fidelity Neural Recording and an Order‐of‐Magnitude Neuromodulation Quality

Abstract

ABSTRACT Neural electrodes face persistent challenges, including inflammation, biofouling, and impedance, which compromise long‐term recording and stimulation quality. Here, we introduced a multifunctional polyamino acid interface that enhances neural interfacing by combining biocompatibility, antimicrobial activity, and antifouling properties. Applied to flexible electrodes, this coating reduces foreign body reaction and preserves neuronal proximity, ensuring stable integration with brain tissue. In chronic rodent models, functionalized electrodes achieve high‐fidelity single‐unit recordings for over 300 days with significantly higher spike amplitudes and yield than bare controls. Notably, the interface enables an order‐of‐magnitude improvement in neuromodulation efficiency, evoking robust motor responses at only 2 µA compared to 100 µA for uncoated probes. Multi‐omics analysis reveals a molecularly profound alteration in the host tissue response, transitioning from a pro‐inflammatory injury signature to an attenuated inflammatory state with improved tissue homeostasis. Furthermore, the interface's resistance to biological “cementing” facilitates damage‐free electrode removal and recovery, preserving the neural architecture and enabling the possibility of chronic replacement. This universal platform offers a promising and practical strategy for the next generation of stable, clinically viable neural–computer interfaces.