Caratterizzazione biomeccanica del tessuto nervoso periferico per la progettazione di interfacce neurali innovative

Questo lavoro ha lo scopo di fornire basi razionali per la progettazione e lo sviluppo di un prototipo di dispositivo neurale che sfrutti una configurazione innovativa, che rende possibile un aumento della selettività del dispositivo e della sua capacità di fornire informazioni ad apparati robotici. Il dispositivo viene in contatto con tessuti biologici viventi quindi la sua progettazione non può prescindere né dalla conoscenza del loro comportamento meccanico, né dalle ripercussioni che si prevedono in una sua eventuale applicazione cronica. Perciò sono stati svolti esperimenti di caratterizzazione meccanica del tessuto nervoso periferico, proveniente da un suino adulto, sottoponendolo sollecitazioni che si prevedono esistenti in condizioni fisiologiche e di applicazione del dispositivo neurale. Dato che il dispositivo necessita dell’inserzione di aghi all’interno del nervo, sono state svolte prove di foratura del tessuto utilizzando aghi metallici geometricamente simili a quelli previsti per il dispositivo. Questo per quantificare le forze in gioco nel processo e poter svolgere uno studio di stabilità elastica agli elementi finiti. Sono stati sviluppati, infine, alcuni modelli matematici approssimati dei comportamenti osservati sperimentalmente per un confronto con futuri modelli FEM

Geometric Characterization of Local Changes in Tungsten Microneedle Tips after In-Vivo Insertion into Peripheral Nerves

Peripheral neural interfaces are used to connect the peripheral nervous system to high-tech robotic devices and computer interfaces. Soft materials are nowadays used to build the main structural part of these interfaces because they are able to mimic the mechanical properties of peripheral nerves. However, if on the one hand soft materials provide effective connections, reducing mechanical mismatch with nervous tissues and creating a close contact between active sites and neural fibers, on the other hand, most of them are not mechanically stable during implantation. As a consequence, tungsten (W) microneedles are used to insert soft neural interfaces, because they are able to pierce the peripheral nervous tissue because of their high stiffness. Nevertheless, this stiffness cannot prevent microneedles from local microscopic structural damage, even after successful insertions. In addition, the nature of this damage is not totally clear. Therefore, this work aimed at quantitatively investigating the phenomenological changes of the microneedles’ tip shape after insertion into the in vivo peripheral nerves. In particular, a quantification of the interactions between peripheral nerves and W microneedles was proposed through the Oliver-Pharr formula, and the interaction force was found to be directly proportional to the power < m > = 2.124 of the normalized indentation depth. Moreover, an experimental correlation between insertion force and the opening tip angle was described together with an assessment of the minimum diameter to effectively puncture the peripheral nervous tissue. Finally, a computational framework was presented to describe the local changes affecting the microneedles’ tip shape. This approach was able to detect a bulging phenomenon along with the microneedle tips with a characteristic amplitude of approximately 100 μm, and a folding phenomenon, with a characteristic mean amplitude of less than 20 μm, affecting the extreme ending sections of the microneedle tips. These geometrical changes were related to the synergistic action of interaction forces likely resulting in compression and elastic instability of the tip

In vivo interactions between tungsten microneedles and peripheral nerves

Tungsten microneedles are currently used to insert neural electrodes into living peripheral nerves. However, the biomechanics underlying these procedures is not yet well characterized. For this reason, the aim of this work was to model the interactions between these microneedles and living peripheral nerves. A simple mathematical framework was especially provided to model both compression of the external layer of the nerve (epineurium) and the interactions resulting from penetration of the main shaft of the microneedle inside the living nerves. The instantaneous Young's modulus, compression force, the work needed to pierce the tissue, puncturing pressure, and the dynamic friction coefficient between the tungsten microneedles and living nerves were quantified starting from acute experiments, aiming to reproduce the physical environment of real implantations. Indeed, a better knowledge of the interactions between microneedles and peripheral nerves may be useful to improve the effectiveness of these insertion techniques, and could represent a key factor for designing robot-assisted procedures tailored for peripheral nerve insertion

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Some Mechanical Constraints to the Biomimicry with Peripheral Nerves

Novel high technology devices built to restore impaired peripheral nerves should be biomimetic in both their structure and in the biomolecular environment created around regenerating axons. Nevertheless, the structural biomimicry with peripheral nerves should follow some basic constraints due to their complex mechanical behaviour. However, it is not currently clear how these constraints could be defined. As a consequence, in this work, an explicit, deterministic, and physical-based framework was proposed to describe some mechanical constraints needed to mimic the peripheral nerve behaviour in extension. More specifically, a novel framework was proposed to investigate whether the similarity of the stress/strain curve was enough to replicate the natural nerve behaviour. An original series of computational optimizing procedures was then introduced to further investigate the role of the tangent modulus and of the rate of change of the tangent modulus with strain in better defining the structural biomimicry with peripheral nerves

Deterministic and Explicit: A Quantitative Characterization of the Matrix and Collagen Influence on the Stiffening of Peripheral Nerves Under Stretch

The structural organization of peripheral nerves enables them to adapt to different body postures and movements by varying their stiffness. Indeed, they could become either compliant or stiff in response to the amount of external solicitation. In this work, the global response of nerves to axial stretch was deterministically derived from the interplay between the main structural constituents of the nerve connective tissue. In particular, a theoretical framework was provided to explicitly decouple the action of the ground matrix and the contribution of the collagen fibrils on the macroscopic stiffening of stretched nerves. To test the overall suitability of this approach, as a matter of principle, the change of the shape of relevant curves was investigated for changes of numerical parameters, while a further sensitivity study was performed to better understand the dependence on them. In addition, dimensionless stress and curvature were used to quantitatively account for both the matrix and the fibril actions. Finally, the proposed framework was used to investigate the stiffening phenomenon in different nerve specimens. More specifically, the proposed approach was able to explicitly and deterministically model the nerve stiffening of porcine peroneal and canine vagus nerves, closely reproducing (R2>0.997) the experimental data

Deterministic control of mean alignment and elongation of neuron-like cells by grating geometry: a computational approach

Neuron-like cells are driven by their surrounding environment through local topography. A causal mechanotransductive web of topography-force relationships influences and controls complex cellular phenomena such as growth and alignment. This work aimed to provide a computational framework able to model the behaviour of neuron-like (PC12) cells on gratings, accounting for the twofold ability of topographical cues to simultaneously align and enhance the growth of cells. In particular, starting from the mechanical behaviour of the growth cone and filopodia, the effect of grating geometry (e.g., the periodicity and the size of grooves and ridges) on the neuritic mean alignment angle and on the outgrowth rate of cells was explored through theoretical tools and combinatorial simulations, which were able to predict (R(2) > 0.9) experimental data in a time range of 72-120 hour

Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves:A hybrid computational approach

Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves