Innovative biomedical applications of electric and magnetic fields on the nervous system

Introduction. In recent decades, the use of innovative technologies has gained increasing significance in clinical and hospital practice, becoming a fundamental auxiliary tool for the treatment and improvement of conditions of patients affected by various pathologies (Han et al., 2024; Junaid et al., 2022; Kulkarni et al., 2024; Varaganti & Seo, 2024). This thesis explores promising biomedical applications involving electric and magnetic fields, which have gained increasing recognition across various medical applications (Mattsson & Simkó, 2019), particularly targeting the nervous system. For therapeutic purposes, this thesis aims to pioneer electroceutical solutions for nervous system pathologies with limited treatment options (Balasubramanian et al., 2024; Famm, 2013). Central to this is spinal cord injury (SCI) research within the FET OPEN European Project RISEUP (grant No. 964562), in which an electrified, implantable scaffold-device, able to stimulate stem cells through ultrashort, intense electrical pulses and direct current, is under development for SCI regeneration. Additionally, potential neuroprotective effects from low-intensity, low-frequency pulsed magnetic fields (LF-PEMFs) are assessed in both a clinical study on ischemic stroke patients (I-NIC project) and an in vitro amyotrophic lateral sclerosis (ALS) fibroblast model. In diagnostics, this thesis also explores wireless capsule endoscopy: an innovative diagnostic tool using a miniaturized ingestible capsule to capture gastrointestinal (GI) biological parameters and images, via integrated electronics, ss part of the involvement in PING project (POR FESR, Lazio region, Italy). Methods. The common approach, adopted throughout the various activities of this thesis, involved the use of advanced computational modeling and numerical dosimetry. These tools provide powerful means to accurately quantify the electrical and magnetic quantities involved, thereby enhancing the control of the biomedical applications investigated and optimizing them for their intended purposes. Results. Within RISEUP, this thesis employs a numerical model of EPB technology and advanced virtual cells to perform accurate microdosimetry of stimulation. This methodology demonstrates EPB's ability to achieve stimulation levels necessary to promote neurogenesis from stem cells, while establishing a protocol to activate key cellular processes and evaluate effects on neuronal behavior. In the context of LF-PEMFs for potential neuroprotection, results from the I-NIC project demonstrate that semi-specific patient models reveal dose-response curves of active patients indicating a significant reduction in ischemic injuries after LF-PEMFs treatment, compared to placebo patients, strongly supporting the hypothesis that stimulation can reduce inflammatory processes. Further possible effects of LF-PEMFs are investigated on ALS progression. A set of cell lines from a familial cluster was prepared for in vitro exposure, supported by a custom 3D dosimetric study to ensure uniform exposure across samples, which allowed for simultaneous exposure and sham experiments with appropriate shielding for controls. Additionally, as part of the PING project, this thesis tackles the lack of studies on wearable localization systems. It will demonstrate through the use of anthropomorphic models how an array of loop antennas can pinpoint the position of the capsule, which continuously acquires and transmits data, within the GI tract, by analyzing the intensity of the received signal. Moreover, another key feature of PING is the implementation of the enteric neuronal sensing, using electrodes embedded in the capsule. The minimum detectable signal estimated through advanced intestinal models will showcase the feasibility of this application. Conclusions. This thesis contributes to the evolving landscape of biomedical applications by advancing the understanding and implementation of electric and magnetic field technologies in both therapeutic and diagnostic contexts. Overall, this work lays a solid foundation for future research aimed at optimizing these technologies, potentially leading to improved treatment strategies and better clinical outcomes for patients facing complex medical conditions.