Minimally invasive magnetic actuation for the treatment of intestinal dysmotility

Intestinal dysmotility disorders represent a major clinical challenge, significantly impairing patients’ quality of life and, in severe cases, requiring invasive procedures that are often unsatisfactory in the long term. Pharmacological treatments are limited by poor specificity and side effects, while surgical approaches carry substantial risks and are not always applicable to fragile patients. In this context, the work presented in this thesis investigated a novel, minimally invasive strategy based on magnetic stimulation of the intestine. The concept relies on the administration of mucoadhesive magnetic nanoparticles that transiently bond the intestinal mucosa and are actuated by external magnets, producing controlled deformations of the bowel wall mimicking physiological peristalsis. The research followed an integrated approach, combining material characterisation, ex vivo experimentation, computational modelling, and prototyping. At the material level, particular attention was addressed to the mucoadhesive functionalisation of Fe₃O₄ nanoparticles. Chitosan was selected as coating material for its biocompatibility and simple preparation. The physicochemical properties, stability in suspension, and mucoadhesive behaviour of the formulation were quantified, together with its biological behaviour. Importantly, the nanoparticles demonstrated cytocompatibility, absence of translocation across the intestinal barrier, and no interference with nutrient absorption, thus confirming their suitability for gastrointestinal applications. The experimental section was complemented by ex vivo magnetic actuation tests, in which porcine tissue loaded with nanoparticles was subjected to external magnetic fields. These tests demonstrated the feasibility of the concept, producing measurable tissue deformations under controlled magnetic stimulation. The displacement values obtained in these experiments served as reference benchmarks for the computational modelling framework, ensuring consistency between theory and practice. The mechanical behaviour of intestinal tissue was investigated through dedicated experiments on porcine jejunum samples. The viscoelastic properties of the tissue were quantified under human physiologically relevant loading conditions, providing key descriptors of both the elastic and viscous components of the response. These results not only offered insight into the time-dependent mechanics of the bowel wall but also served as the foundation for computational modelling. Building on this foundation, a comprehensive computational model was developed using finite element methods. The model explicitly included the Kelvin force formulation to describe the interaction between magnetic fields and nanoparticle-loaded tissues. After calibration with experimental data through parameter sweeps and mesh convergence analysis, the model was used to explore magnetic stimulation patterns. Several optimisation domains were investigated, including densification of Halbach arrays, multilayer arrangements, asymmetric layouts, selective out-of-plane rotations of magnets, and the use of ferromagnetic flux concentrators. Each strategy provided insight into the physics of magnetic field generation and redistribution, while also offering quantitative guidelines for practical implementation. The overall results demonstrated that carefully optimised multi-magnet systems, integrated with ferromagnetic elements, can significantly increase field intensity in the intestinal region while retaining controllability and modularity. As a proof of concept, a reduced section of the elliptical belt, including three magnets on three layers, was designed, 3D-printed, and assembled with stepper motor actuation. The electronic module, controlled by an Arduino platform, successfully coordinated rotational and translational movements, demonstrating that controlled multi-magnet actuation can be achieved with compact and accessible components. Although limited in scale and simplified compared to the envisioned final system, the prototype provided a practical validation of the concept and established the groundwork for more advanced future devices. To set the ground for the future validation of the strategy, the definition of an intestinal physical phantom replicating gut architecture and mechanics is required. A PDMS-based phantom functionalised with APTES was thus fabricated demonstrating the feasibility of replicating the anatomy of a tract of human gut and its elastic behaviour. Future analysis will be directed to replicating the viscoelastic component in addition to tissue anisotropy. This conclusion directly aligns with the principles of the 3Rs, paving the way for animal free experimental models. Overall, key next steps include translation to pathological human tissue, refinement of synthetic phantoms and the integration of the magnetic actuation system in a baby walker for paediatric use. The results presented here establish a solid scientific and engineering foundation for the future development of magnetic stimulation systems as minimally invasive therapies for intestinal dysmotility. By bridging material science, biomechanics, computational modelling, and device engineering, this work not only proves the concept but also opens the way to clinical translation, with the potential to provide patients with a controllable, adaptable, and non-invasive alternative to current therapies.