Neuromodulation of a peripheral nerve using fully polymeric cuff electrodes: Understanding predictability of selective stimulation

Peripheral nerve stimulation (PNS) offers therapeutic benefits across numerous clinical applications but suffers from limitations in high resolution spatial selectivity, especially in mixed nerves. This study presents a fully polymeric, transverse, multipolar nerve cuff made from a conductive elastomer (CE), designed for selective activation of individual fascicles. Fabricated with laser-based manufacturing techniques, the CE nerve cuff offers mechanical conformity and high charge injection capacity. Ex vivo experiments on the rat sciatic nerve demonstrate reliable compound action potential recordings and fascicular selectivity (SI > 0.65). The non-metal electrodes enable microCT-aided 3D reconstruction of nerve-electrode geometries without imaging artefacts, informing anatomically accurate simulations via the ASCENT pipeline. While in silico simulations predict some selective fascicular activation, discrepancies were observed between predicted and experimental selectivity magnitudes and electrode positions, particularly for the sural and tibial fascicles. The model was more sensitive to neuroanatomical variation than the experimental data, indicating limitations in current perineurium and CE electrode modelling assumptions. This work validates CE-based cuffs as viable alternatives to metallic devices for selective fascicular peripheral nerve activation and highlights the potential of imaging-informed simulations to optimize nerve interface design. Future improvements in electrode and nerve tissue modelling are needed to enhance in silico prediction accuracy and further advance spatially selective PNS technologies.