In-Vivo Quantification of Knee Deep-Flexion in Physiological Loading Condition trough Dynamic MRI

The in-vivo quantification of knee motion in physiological loading conditions is paramount for the understanding of the joint’s natural behavior and the comprehension of articular disorders. Dynamic MRI (DMRI) represents an emerging technology that makes it possible to investigate the functional interaction among all the joint tissues without risks for the patient. However, traditional MRI scanners normally offer a reduced space of motion, and complex apparatus are needed to load the articulation, due to the horizontal orientation of the scanning bed. In this study, we present an experimental and computational procedure that combines an open, weight-bearing MRI scanner with an original registration algorithm to reconstruct the three-dimensional kinematics of the knee from DMRI, thus allowing the investigation of knee deep-flexion under physiological loads in space. To improve the accuracy of the procedure, an MR-compatible rig has been developed to guide the knee flexion of the patient. We tested the procedure on three volunteers. The overall rotational and positional accuracy achieved are 1.8◦ ± 1.4 and 1.2 mm ± 0.8, respectively, and they are sufficient for the characterization of the joint behavior under load

Fabrication and characterization of biomimetic hydroxyapatite thin films for bone implants by direct ablation of a biogenic source

Biomimetic bone apatite coatings were realized for the first time by the novel Ionized Jet Deposition technique. Bone coatings were deposited on titanium alloy substrates by pulsed electron ablation of deproteinized bovine bone shafts in order to resemble bone apatite as closely as possible. The composition, morphology and mechanical properties of the coatings were characterized by GI-XRD, FT-IR, SEM-EDS, AFM, contact angle measurements, micro-scratch and screw-insertion tests. Different post-treatment annealing conditions (from 350 °C to 425 °C) were investigated. Bone apatite coatings exhibited a nanostructured surface morphology and a composition closely resembling that of the deposition target (i.e. natural bone apatite), also regarding the presence of magnesium and sodium ions. Crystallinity and composition of the coatings were strongly influenced by annealing temperature and duration; in particular, upon annealing at 400 °C and above, a crystallinity similar to that of bone was achieved. Finally, adhesion to the titanium substrate and hydrophilicity were significantly enhanced upon annealing, all characteristics being known to have a strong positive impact on promoting host cells attachment, proliferation and differentiation

Osteogenic Differentiation of hDPSCs on Biogenic Bone Apatite Thin Films

A previous study reported the structural characterization of biogenic apatite (BAp) thin films realized by a pulsed electron deposition system by ablation of deproteinized bovine bone. Thin films annealed at 400 degrees C exhibited composition and crystallinity degree very close to those of biogenic apatite; this affinity is crucial for obtaining faster osseointegration compared to conventional, thick hydroxyapatite (HA) coatings, for both orthopedics and dentistry. Here, we investigated the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells (hDPCS) on as-deposited and heat-treated BAp and stoichiometric HA. First, we showed that heat-treated BAp films can significantly promote hDPSC adhesion and proliferation. Moreover, hDPSCs, while initially maintaining the typical fibroblast-like morphology and stemness surface markers, later started expressing osteogenic markers such as Runx-2 and OSX. Noteworthy, when cultured in an osteogenic medium on annealed BAp films, hDPSCs were also able to reach a more mature and terminal commitment, with respect to HA and as-deposited films. Our findings suggest that annealed BAp films not only preserve the typical biological properties of stemness of, hDPSCs but also improve their ability of osteogenic commitment

Ab-initio Quantum Enhanced Optical Phase Estimation Using Real-time Feedback Control

Optical phase estimation is a vital measurement primitive that is used to perform accurate measurements of various physical quantities like length, velocity and displacements. The precision of such measurements can be largely enhanced by the use of entangled or squeezed states of light as demonstrated in a variety of different optical systems. Most of these accounts however deal with the measurement of a very small shift of an already known phase, which is in stark contrast to ab-initio phase estimation where the initial phase is unknown. Here we report on the realization of a quantum enhanced and fully deterministic phase estimation protocol based on real-time feedback control. Using robust squeezed states of light combined with a real-time Bayesian estimation feedback algorithm, we demonstrate deterministic phase estimation with a precision beyond the quantum shot noise limit. The demonstrated protocol opens up new opportunities for quantum microscopy, quantum metrology and quantum information processing.Comment: 5 figure

Corrigendum to “Osteogenic Differentiation of hDPSCs on Biogenic Bone Apatite Thin Films”

In the article titled "Osteogenic differentiation of hDPSCs on biogenic bone apatite thin films" [1], the second affiliation was incorrect. The corrected affiliations are shown above

The human meniscus behaves as a functionally graded fractional porous medium under confined compression conditions

In this study, we observe that the poromechanical parameters in human meniscus vary spatially throughout the tissue. The response is anisotropic and the porosity is functionally graded. To draw these conclusions, we measured the anisotropic permeability and the “aggregate modulus” of the tissue, i.e., the stiffness of the material at equilibrium, after the interstitial fluid has ceased flowing. We estimated those parameters within the central portion of the meniscus in three directions (i.e., vertical, radial and circumferential) by fitting an enhanced model on stress relation confined compression tests. We noticed that a classical biphasic model was not sufficient to reproduce the observed experimental behaviour. We propose a poroelastic model based on the assumption that the fluid flow inside the human meniscus is described by a fractional porous medium equation analogous to Darcy’s law, which involves fractional operators. The fluid flux is then time-dependent for a constant applied pressure gradient (in contrast with the classical Darcy’s law, which describes a time independent fluid flux relation). We show that a fractional poroelastic model is well-suited to describe the flow within the meniscus and to identify the associated parameters (i.e., the order of the time derivative and the permeability). The results indicate that mean values of λβ,β in the central body are λβ=5.5443×10−10m4Ns1−β, β=0.0434, while, in the posterior and anterior regions, are λβ=2.851×10−10m4Ns1−β, β=0.0326 and λβ=1.2636×10−10m4Ns1−β, β=0.0232, respectively. Furthermore, numerical simulations show that the fluid flux diffusion is facilitated in the central part of the meniscus and hindered in the posterior and anterior regions

Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue

BackgroundIn light of recent developments in nanotechnologies, interest is growing to better comprehend the interaction of nanoparticles with body tissues, in particular within the cardiovascular system. Attention has recently focused on the link between environmental pollution and cardiovascular diseases. Nanoparticles <50 nm in size are known to pass the alveolar¿pulmonary barrier, enter into bloodstream and induce inflammation, but the direct pathogenic mechanisms still need to be evaluated. We thus focused our attention on titanium dioxide (TiO2) nanoparticles, the most diffuse nanomaterial in polluted environments and one generally considered inert for the human body.MethodsWe conducted functional studies on isolated adult rat cardiomyocytes exposed acutely in vitro to TiO2 and on healthy rats administered a single dose of 2 mg/Kg TiO2 NPs via the trachea. Transmission electron microscopy was used to verify the actual presence of TiO2 nanoparticles within cardiac tissue, toxicological assays were used to assess lipid peroxidation and DNA tissue damage, and an in silico method was used to model the effect on action potential.ResultsVentricular myocytes exposed in vitro to TiO2 had significantly reduced action potential duration, impairment of sarcomere shortening and decreased stability of resting membrane potential. In vivo, a single intra-tracheal administration of saline solution containing TiO2 nanoparticles increased cardiac conduction velocity and tissue excitability, resulting in an enhanced propensity for inducible arrhythmias. Computational modeling of ventricular action potential indicated that a membrane leakage could account for the nanoparticle-induced effects measured on real cardiomyocytes.ConclusionsAcute exposure to TiO2 nanoparticles acutely alters cardiac excitability and increases the likelihood of arrhythmic events

A multidisciplinary experimental framework addressing the relationship between the mechanical behaviour and the structure of the knee articular cartilage

La cartilagine è un tessuto connettivo specializzato, facente parte delle articolazioni sinoviali. Il comportamento meccanico della cartilagine – che contribuisce alla funzione di smorzamento delle forze svolta dai tessuti che compongono l’unità fondamentale delle articolazioni sinoviali, nota come unità osteocondrale – risulta essenziale per ridistribuire le forze multi-assiali che si sviluppano all’interno delle articolazioni stesse il movimento. L’interazione dinamica tra omeostasi e rimodellamento dei tessuti che costituiscono l’unità osteocondrale è cruciale per garantire la funzionalità articolare. Molteplici patologie di natura traumatica e degenerativa possono deteriorare il rimodellamento dinamico dei tessuti osteocondrali, specialmente considerando articolazioni altamente sollecitate come quella del ginocchio. Una conoscenza esaustiva dei tessuti osteocondrali è essenziale per comprendere l’insorgenza e la progressione di patologie che compromettono la funzionalità delle articolazioni sinoviali, in particolare con l’obiettivo di evidenziare i principali aspetti e fenomeni su cui i relativi trattamenti dovrebbero concentrarsi. In questa prospettiva, gli approcci attualmente impiegati nello studio dei tessuti osteocondrali – in particolare, volti all’indagine del loro comportamento meccanico, e della loro struttura e composizione – sono ben lontani dal fornire informazioni attendibili, riproducibili e complete, soprattutto in merito alla cartilagine articolare. Nello specifico, gli studi sperimentali ex-vivo che valutano le peculiarità della cartilagine articolare si focalizzano su tale tessuto dopo la sua separazione dalla struttura dell’unità osteocondrale, fornendo informazioni integrate a partire da approcci multidisciplinari solo in alcuni casi. Nell’ambito di questa tesi di dottorato, un approccio sperimentale e multidisciplinare è stato sviluppato con l’obiettivo di esaminare la relazione tra funzionalità e struttura di uno dei tessuti che compongono l’unità osteocondrale del ginocchio, nello specifico la cartilagine articolare, con particolare attenzione alla sua biomeccanica. Nonostante le metodiche proposte siano state sviluppate tenendo conto delle particolarità del tessuto cartilagineo, le peculiarità alla base delle stesse sono state definite con lo scopo di estendere la loro applicazione allo studio dell’intera unità osteocondrale. In primo luogo, è stato ottimizzato un protocollo di test basato sulla metodica di indentazione per investigare il comportamento viscoelastico del tessuto cartilagineo; l’implementazione di un protocollo di test standardizzato risulta essenziale per ottenere informazioni affidabili e riproducibili sulla biomeccanica della cartilagine articolare. In secondo luogo, la relazione tra funzionalità e struttura/composizione di tale tessuto è stata studiata applicando il protocollo di test precedentemente ottimizzato, e un approccio sperimentale basato su spettroscopia. Inoltre, considerando sia l’obiettivo principale della tesi, ma nella prospettiva di investigare l’unità osteocondrale nella sua interezza, è stato utilizzato uno specifico agente di contrasto per imaging basato su X-ray con l’obiettivo di ottenere informazioni in merito alla composizione della cartilagine articolare. Infine, è stata valutata l’idoneità di un approccio comprensivo basato su raggi X per lo studio del comportamento meccanico dell’unità osteocondrale. L'approccio multidisciplinare proposto rappresenta un importante passo in avanti nello studio delle caratteristiche principali del tessuto cartilagineo di ginocchio, offrendo la potenzialità di valutare appropriatamente l’efficacia di terapie e di approcci di ingegneria tessutale volte alla cure delle patologie articolari.Articular cartilage is an extremely specialized connective tissue composing the synovial joints. The response of articular cartilage – along with the damping system provided by the other tissues composing the fundamental unit of synovial joints, i.e., the osteochondral unit – is essential in deploying multiaxial forces generated during locomotion. The dynamic interaction between homeostasis and remodelling of the osteochondral tissues is essential in maintaining joints functional capabilities. Several traumatic and degenerative pathologies may deregulate the dynamic remodelling of the osteochondral tissues, especially considering highly-stressed articulation as the knee joint. The knowledge on osteochondral tissues is essential in understanding the onset and progression of several pathologies affecting synovial joints, moreover, allowing to elucidate the main aspects on which relative treatments should focus on. In this perspective, the approaches investigating the peculiarities – i.e., mechanical response, structure, and composition – of such a unit are away far from providing reliable and complete information, particularly concerning articular cartilage. Ex-vivo studies focusing on the knee articular cartilage mostly evaluate such a tissue through single-layer tests, yielding insights through multidisciplinary approaches only occasionally. Within this thesis, a multidisciplinary experimental framework was developed to explore the relationship between functionality and structure of one of the three tissues composing the knee osteochondral unit, the articular cartilage, with a particular focus on tissue biomechanics. Although the approaches here proposed were tailored to articular cartilage, the peculiarities at the base of these techniques are defined aiming to extend their application to study the features of the osteochondral unit in a comprehensive way. First, an indentation protocol was optimized to investigate the articular cartilage viscoelastic response; the implementation of a reliable mechanical testing protocol is crucial to achieve reliable insight on the mechanical response of articular cartilage. Second, the relationship between articular cartilage functionality – i.e., mechanical response – and structure/composition has been investigated, evaluating articular cartilage through the previously optimized indentation protocol and, moreover, an experimental, spectroscopic-based approach. Third, considering the previously mentioned purpose and, further, moving towards a comprehensive evaluation of the osteochondral unit, the use of a specific contrast-agent X-ray imaging was explored to investigate the articular cartilage composition. Fourth, we assessed also the suitability of a full-field, X-ray-based approach in studying the comprehensive functional behaviour of the osteochondral unit. The implemented multidisciplinary framework represents a key step forward investigating the main features of the knee articular cartilage, providing the potential of assessing properly the efficacy of clinical and tissue-engineering treatments addressing the pathologies of the knee

Valutazione delle forze di fissazione di scaffold magnetici di ultima generazione per la rigenerazione ossea

La riparazione del tessuto osseo e cartilagineo, in conseguenza a fattori esterni (traumi) oppure a problematiche interne (osteoporosi, necrosi ossea), rappresenta una delle più ardue sfide in ambito chirurgico, ortopedico e riabilitativo. I metodi utilizzati per la loro trattazione si riconducono all’adozione di diverse metodologie di fissazione del tessuto osseo e cartilagineo, che prevedono l’uso di appositi dispositivi, fissatori interni ed esterni. Queste tecniche, nonostante abbiano permesso un importante passo avanti in ambito ortopedico, non sono esenti da problematiche, quali l’invasività delle operazioni per il loro posizionamento in situ, le possibili infezioni ed il relativo rigetto da parte del paziente. Per questo motivo, negli ultimi anni, l’Ingegneria Tissutale ha introdotto un metodo alternativo, che può comunque essere usato al fianco delle procedure sopra descritte, che prevede l’utilizzo di innesti ossei appositamente progettati, gli scaffold. Lo scopo di questa tesi è descrivere l’attività di tirocinio svolta presso il Laboratorio di Biomeccanica degli Istituti Ortopedici Rizzoli durante il quale si sono analizzati diversi processi di fissazione in ambito di danneggiamento ossei di un ultima tipologia di innesti ossei, gli scaffold magnetic