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No description available.

Spinal cord injury is a devastating neurological disorder partially characterized by a loss of motor function below the lesion. The dramatic loss of activity results in muscle atrophy and slow-to-fast transformation of contractile elements, producing smaller, weaker and more fatiguable muscles. Functional electrical stimulation (FES), has been proposed in order to induce muscular activity and reverse these changes. FES has primarily been applied in the periphery, either at the surface or implanted in or around a nerve or muscle. Although this can excite nervous tissue and produce muscular contractions, these systems often produce reversed recruitment of motor units leading to inappropriate force generation and increased fatigue. We applied intraspinal microstimulation (ISMS) through fine microwires implanted into the spinal cord of rats. Electrical stimulation through these microwires caused contractions of the quadriceps muscles in both acute and chronically spinalized animals. We showed that muscle recruitment is significantly more gradual with ISMS in intact rats compared to that produced by a standard nerve cuff. Our results further showed that this was due to preferential activation of fatigue resistant muscle fibers. Given this more orderly recruitment of motor units by ISMS, we tested the muscle phenotypes produced by ISMS or nerve cuffs after chronic stimulation. Surprisingly, over a 30 day stimulation period the quadriceps muscles chronically activated by either daily ISMS or nerve cuff stimulation underwent similar fast-to-slow transformations in fiber type and functional properties. This indicates that the recruitment order of motor units does not play the only role in determining the muscle phenotype. Other factors such as the total daily time of activity may be critically important to the phenotypic outcome of skeletal muscle. Finally, we demonstrated that quadriceps force recruitment by ISMS was unchanged following the 30 day stimulation period. In addition, 30 days of chronic ISMS did not cause observable damage in the spinal cord beyond that incurred by the implantation of sham microwires. These studies advance our understanding of the force recruitment properties, neuromuscular plasticity and damage incurred by ISMS and move us closer to developing a clinically viable ISMS procedure.

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Spinal cord injury causes the partial or total loss of the anatomical and functional continuity of the spinal cord tissue, leading to the damage of the organs controlled by nerves that branch off downstream the injury. This thesis analyses the mechanics of two possible treatments based on two different approaches: intraspinal microstimulation (ISMS) and tissue engineering. These two approaches have a common rationale, the delivery of electrical stimuli to the injured spinal cord. In the literature, the feasibility of the electrodes for ISMS is often limited to the analysis of stiffness. The mechanical validation of the device is then focused on the step after the in vivo implantation, considering the interplay with the surrounding tissue. In this work, the mechanical performance of an innovative intraspinal microstimulation device is evaluated thoroughly before the in vivo step, to avoid the waste of material, animals, and time. The study involves the characterisation of the single components (electrodes), prototypes, and possible failure mechanisms. A work on silk fibroin hydrogels for the regeneration of the spinal cord is also presented. Silk fibroin is a highly versatile material for biomedical purposes, and thus largely used in tissue engineering. Moreover, it has piezolectric properties subjected to micro and nanostructure. Given the proven benefits of electrical stimulation in the regeneration of the spinal cord after injury, different approaches studied in literature often require the use of external devices to generate electrical stimuli. This thesis aims to study the mechanical properties of silk fibroin hydrogels obtained by applying an electric field to silk fibroin solutions, to investigate the eventual increase of the microstructure orientation and consequent improvement of the piezoelectric effects of fibroin.

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Undulatory locomotion is a common and powerful strategy used in nature at different biological scales by a broad range of living organisms, from flagellated bacteria to prehistoric snakes, which have overcome the complexity of living in ”flowable” media. By taking inspiration from this evolution-induced strategy, we aim at modelling the locomotion in a granular and viscous environment with the objective to provide more insights for designing robots for soil-like media exploration. Moreover, in contrast to common types of movement, the granular locomotion is still not well understood and is an open and challenging field. We approached this phenomenon with several tools: (i.) numerically, via coupling the Finite Element Method (FEM) with the Discrete Element Method (DEM) using ABAQUS; (ii.) analytically, by employing the Lagrangian formalism to derive the equations of motion of a discrete and continuous system subject to non-conservative forces, and (iii.) experimentally, by creating an ad-hoc set up in order to observe the migration of microfibres used for the treatment of spinal cord injuries. The computational attempts to model the motion in a granular medium involved the simulation of the dynamics of an elastic beam (FEM) surrounded by rigid spherical particles (DEM). A propulsion mechanism was introduced by sinusoidally forcing the beam’s tip normally to the longitudinal axis, while the performance of the locomotion was evaluated by means of a parametric study. Depending on the parameters of the external excitation, after a transient phase, the slender body reached a steady-state with a constant translational velocity. In order to gain physical insights, we studied a simplified version of the previous continuous beam by introducing a discrete multi-bar system. The dynamics of the latter was analytically derived, by taking into account the forces exchanged between the locomotor and the environment, according to the Resistive Force Theory. By numerically solving the equations of motion and evaluating the input energy and dissipations, we were able to define the efficiency and thus provide an effective tool to optimise the locomotion. It is worth mentioning that the two approaches, despite the different physical hypothesis, show a qualitatively and quantitatively good accordance. The numerical and analytical models previously analysed have shown promising results for the interpretation of "ad-hoc" experiments that demonstrate the migration of a microfibre embedded in a spinal cord-like matrix. This migration needs to be avoided, once the regenerative microfibre is implanted in the lesioned spinal cord, for the sake of the patients health.

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