Dynamic biophysical coupling in bioelectronic interfaces for peripheral nerve modulation

Abstract

Peripheral nerve interfaces provide a bidirectional electrical link between implanted electronics and the peripheral nervous system, supporting therapies for sensory restoration, motor control and chronic disease management. Their long-term performance depends less on how well signals are transmitted at implantation and more on how the electrode–tissue relationship changes, as impedance, threshold, signal fidelity and selectivity drift over months to years. This Review describes these changes through dynamic biophysical coupling, in which mechanical, geometric, electrochemical, biochemical and biological variables co-evolve at the electrode–tissue interface and together determine how the device functions. In this view, keeping coupling within a useful operating window is not a one-time goal set at implantation but a state that must be maintained through coordinated design across materials, device structures, anatomy-specific implantation and system design. We then consider how coupling is measured, modelled and evaluated over the long term, and identify the shared metrics that would make next-generation peripheral nerve interfaces predictable and clinically scalable. Peripheral nerve interfaces typically fail not from acute signal loss but from slow drift in the electrode–tissue relationship. This Review reframes that drift through dynamic biophysical coupling, a unifying view of how materials, structures, anatomy and feedback control together keep interfaces stable, selective and predictable across years of implantation.