Organotypic human brain slice cultures as a translational testing platform for novel neuromodulation devices

Abstract Objective. To establish organotypic human brain slice cultures (hBSCs) as a translational screening platform for evaluating novel neuromodulation devices and to demonstrate the feasibility of the model using magnetoelectric nanoparticles (MENPs) as a representative neurostimulation modality. Approach. Viable hBSCs were prepared from resected cortical tissue of epilepsy surgery patients and GCaMP-based calcium imaging, multi-electrode array recordings, and immunohistochemical staining for c-Fos were conducted. The MENPs were injected into the hBSCs and stimulated with an alternating magnetic field to assess their neuromodulatory effects. Main Results. GCaMP transduction enables the real-time visualization of MENP-induced neuronal activity. Electrophysiological signals, including spiking and local field potentials, were observed in fresh, but not cultured, slices. c-Fos immunostaining revealed a significant increase in c-Fos expression in stimulated MENP-injected cultures compared to sham-treated controls. This protocol yielded reproducible tissue viability and consistent results across patient-derived samples. Significance. This technical note demonstrates that hBSCs represent a reproducible and ethically preferable translational model suitable for screening applications in neurotechnology research. The platform enables early-stage functional evaluation of neuromodulatory devices, particularly those with a higher risk of failure in vivo or curiosity-driven early-phase concepts in a setting superior to traditional in vitro approaches. This platform may help reduce reliance on animal models in neurotechnology development.