Mirkiani, S.; Matter, L.; Arefadib, A.; Sari, K.; Tyreman, N.; Asplund, M.; Mushahwar, V. K.

Restoration of motor function after spinal cord injury remains a major challenge, as existing neuromodulation strategies such as epidural stimulation suffer from limited selectivity. Intraspinal microstimulation (ISMS) offers higher spatial precision but has been constrained by manually fabricated microwire arrays that lack reproducibility, depth control, and mechanical compatibility with neural tissue. Here, we present flex-ISMS, a thin-film, polyimide-based ISMS array integrating 42 stimulation sites distributed across 14 flexible arms. Acute in vivo implantation into the lumbosacral enlargement of domestic pigs demonstrated depth-specificity, site-selectivity and near normal recruitment of motor units resulting in graded contractions in muscles controlling the hip, knee, and ankle joints, with ranges of motion and isometric force generation approaching levels seen during natural locomotion (e.g., 40 deg and 30 N for knee extension). Importantly, electrodes separated by 500 micrometer evoked distinct responses, underscoring submillimetre-scale selectivity. The high flexibility allows the device to conform to the spinal cord while displacing tissue by only 40x8 micrometer per arm. Histological analyses showed that the 125 micrometer diameter tungsten insertion aid of the flex-ISMS arms produced minimal acute damage, indistinguishable from that produced by conventional 50 micrometer diameter microwires. These acute outcomes establish the surgical feasibility and functional capability of flex-ISMS, and provide the foundation for forthcoming chronic studies in spinal-cord-injured models.