Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges

The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis

Distribution and origin of natural gas leakage in the Colorado Basin, offshore Argentina Margin, South America : seismic interpretation and 3D basin modelling

The detailed analysis of a dense 2D seismic reflection dataset and data from 8 exploration wells, allowed us to identify, map out and characterize possible indications of past and present-day hydrocarbon leakage (i.e. gas chimneys, gas pockets, and seafloor mounds and pockmarks) on the continental shelf and slope of the Colorado Basin, offshore Argentina, where Permian, Jurassic and Early Cretaceous source rocks are potentially present and may be currently mature. Identified gas leakage features, developed both in the syn-rift and post-rift successions, were also analysed in relation to the structural the stratigraphic elements of the basin. A family of seabed pockmarks, located close to an array of submarine channels, was identified on the distal slope of the basin. These pockmarks are overlying a series of sub-vertical to vertical seismic chimneys in the subsurface. A calibrated basin-wide 3D petroleum system model comprising generation and migration of hydrocarbons was carried out and compared with the observations from the seismic analysis. Preliminary results from this model indicate that although synrift and early Cretaceous source rock (SR) intervals may be depleted in the central areas of the basin, an active kitchen from the Aptian SR may be present below the slope areas. Hydrocarbon migration pathways predicted by the 3D model (Hybrid method) coincide with the interpreted seismic chimneys underlying the observed seabed slope pockmarks. Hence, our results indicate that thermogenic gas may be currently generated in the distal slope of the basin from mature early post-rift source rocks within the Early Cretaceous (Aptian) sequences and migrates vertically, due to seal failure, through the stratigraphic column. This migrating thermogenic gas is feeding the seafloor pockmarks identified in the distal slope of the basin, although up-dip lateral migration along stratigraphic layers to the more proximal slope areas cannot be ruled out. The present work represents the first published study integrating detailed seismic analysis and 3D basin modelling linking observed gas-leakage indicators and associated seepage pathways, to their relative abundance, distribution and feeding systems offshore Argentina's continental margin

Recanalization of the Native Artery in Patients with Bypass Failure

Our objective was to evaluate the possible role of endovascular recanalization of occluded native artery after a failed bypass graft in the case of either acute or chronic limb-threatening ischemia otherwise leading to amputation. In a single-center retrospective clinical analysis, from January 2004 to March 2007 we collected 31 consecutive high-surgical-risk patients (32 limbs) with critical limb ischemia following late ([30 days after surgery) failure of open surgery bypass graft reconstruction. All patients deemed unfit for surgery underwent tentative endovascular recanalization of the native occluded arterial tract. The mean follow-up period was 24 (range, 6–42) months. Technical success was achieved in 30 (93.7%) of 32 limbs. The cumulative primary assisted patency calculated by Kaplan–Meyer analysis was 92% and 88%, respectively, at 12 and 24 months. The limb salvage rate approached 90% at 30 months. In conclusion, our experience shows the feasibility of occluded native artery endovascular recanalization after a failed bypass graft, with optimal results in terms of midterm arterial patency and limb salvage. Our opinion is that successful recanalization of the arterial tract previously considered unsuitable for endovascular approach is allowed by improved competency and experience of vascular specialists, as well as the advances made in catheter and guidewire technology. This group of patients would previously have been relegated to repeat bypass grafts, with their inherently inferior patency and recognized added technical demands. We recognize previous surgical native artery disconnection and lack of pedal runoff to be the main cause of technical failure. Keywords Native artery Bypass failure Endovascular recanalizatio

A system of coupled Cahn-Hilliard equations

LAUREA MAGISTRALEIl presente lavoro di tesi è dedicato all'analisi matematica di un sistema di equazioni di Cahn-Hilliard accoppiate, proposto per modellizzare la dinamica di alcune soluzioni polimeriche. Nonostante siano disponibili simulazioni numeriche per questo sistema, è ancora assente uno studio teorico, anche nel caso di nonlinearità regolari. L'obiettivo della tesi è di muovere i primi passi verso un'analisi rigorosa dei sistemi formati da equazioni di questo tipo. In particolare, trattiamo un sistema formato da un'equazione di Cahn-Hilliard accoppiata ad una di Cahn-Hilliard-Oono. Tale sistema descrive la dinamica di una miscela costituita da un copolimero a due blocchi e un omopolimero. Consideriamo un potenziale di interazione in due variabili, formato sia da una parte singolare sia da una regolare. Questa scelta è fisicamente più rilevante rispetto al modello originale, poiché le entropie di miscelazione non sono approssimate. Tuttavia, tale scelta rende l'analisi del sistema più complicata. Proviamo anzitutto l'esistenza di una soluzione debole tramite un doppio schema di approssimazione. I potenziali di Flory-Huggins contenenti le entropie di miscelazione sono approssimati da potenziali regolari a doppio pozzo. Il problema approssimante risultante è dunque risolto tramite uno schema di Galerkin. Si ottiene poi la soluzione debole cercata passando al limite sui parametri di regolarizzazione dei potenziali. Ottenuta una soluzione debole, proviamo che è unica tramite la dipendenza continua dai dati iniziali. Mostriamo infine alcune proprietà di regolarizzazione della soluzione debole, essenziali per ulteriori risultati (e.g. comportamento ai tempi lunghi). Il contenuto della tesi è così strutturato. Nel Capitolo 1 sono presentati il contesto e la derivazione dell'equazione di Cahn-Hilliard e di Oono. Il sistema accoppiato e i problemi al bordo e ai valori iniziali sono derivati nel Capitolo 2. I risultati di buona positura e la loro ambientazione funzionale sono enunciati nel Capitolo 3 e dimostrati nel Capitolo 4. I risultati sulla regolarizzazione in tempo finito sono trattati nel Capitolo 5, mentre il Capitolo 6 è dedicato alle conclusioni e a problematiche future.The present thesis is devoted to the mathematical analysis of a system of coupled Cahn-Hilliard equations, proposed to model the dynamics of certain mixtures of polymers. Although numerical simulations for this system are available, a theoretical investigation is still lacking, even in the framework of regular nonlinearities. The aim of the present thesis is to move the first steps towards a rigorous analysis of equations of this kind. In particular, here we consider a system which consists of a Cahn-Hilliard equation coupled with a Cahn-Hilliard-Oono equation. This system describes the dynamics of a mixture consisting of a diblock copolymer and a homopolymer. We consider a bivariate interaction potential including both a singular and a regular part. This choice is physically more relevant with respect to the original model, because the entropies of the mixtures are not approximated. On the other hand, this choice makes the mathematical analysis more challenging. We first prove the existence of a weak solution through a double approximation scheme. The Flory-Huggins potentials containing the mixing entropies are approximated by regular double-well potentials. The resulting approximating problem is then solved through a Galerkin scheme. Then we get the wanted weak solution by passing to the limit in the regularization parameters of the potentials. Once we have a weak solution, we prove that it is unique as a consequence of the continuous dependence on the initial data. Finally, we establish some regularization properties of the weak solution, which are essential steps towards further results (e.g. the long-time behaviour). The contents of the thesis are structured as follows. In Chapter 1, the context and the derivation of the Cahn-Hilliard equation, as well as its Oono variant, are presented. The coupled system and the related initial and boundary value problem are derived in Chapter 2. The well-posedness results and their functional setting are stated in Chapter 3 and proven in Chapter 4. The results about the regularization in finite time are stated and demonstrated in Chapter 5, while Chapter 6 is devoted to conclusions and future issues

Deterministic and stochastic analysis of some diffuse interface models

DOTTORATOLa presente tesi si concentra sull'analisi matematica di diversi modelli deterministici e stocastici ad interfaccia diffusa. Questi sistemi forniscono una buona descrizione dei fenomeni di separazione di fase che si verificano in materiali complessi come leghe binarie, miscele fluide multicomponenti o miscugli polimerici. La denominazione interfaccia diffusa si riferisce al fatto che l'interfaccia tra due specie diverse è considerata una regione di spazio con spessore finito. Dopo aver illustrato il materiale preliminare nei Capitoli 1 e 2, i principali contributi contenuti in questa tesi sono presentati in due parti: la prima tratta i modelli deterministici, mentre la seconda è dedicata a quelli stocastici. Tuttavia, in tutti i modelli discussi, ci proponiamo di lavorare all'interno del quadro fisico. Infatti, se il funzionale energia del sistema è termodinamicamente consistente, allora è possibile dimostrare che una soluzione ha significato fisico (ovvero che assume valori fisicamente ammissibili). Il metodo principale per raggiungere questo obiettivo consiste nel modellizzare l'energia potenziale del sistema attraverso una funzione le cui derivate presentano barriere di potenziale. Infatti, questo approccio garantisce che qualsiasi soluzione con energia finita sia confinata all'interno di tali barriere. Presentiamo ora i contributi contenuti nella prima parte di questa tesi. Nel Capitolo 3, esaminiamo un modello per miscele polimeriche elettricamente reattive. In particolare, siamo interessati a miscele formate da copolimeri a due blocchi e da un omopolimero che funge da solvente. La separazione di fase che avviene tra copolimero e omopolimero, così come quella tra i due blocchi del copolimero, permette l'autoassemblaggio di strutture ordinate a livello mesoscopico che si rivelano utili anche nello sviluppo di nanotecnologie. In questo modello, le interazioni maxwelliane giocano un ruolo significativo, in quanto l'applicazione di campi elettrici esterni è uno dei metodi principali per indurre la formazione di pattern. Il Capitolo 4 illustra, in un contesto leggermente diverso, l'altra faccia delle interazioni maxwelliane. In esso si considera un modello che descrive fluidi complessi magneticamente reattivi, tenendo conto degli effetti idrodinamici e delle interazioni tra fluidi diversi. Infine, l'ultimo sistema deterministico, analizzato nel Capitolo 5, descrive un sistema ternario in cui due fluidi sono mescolati con un tensioattivo. Questo tipo di sostanze è in grado di ridurre la tensione interfacciale tra fluidi diversi e di consentire il mescolamento di fluidi normalmente immiscibili (ad esempio, acqua e olio). Nei modelli sopra menzionati, i problemi matematici ricorrenti riguardano l'esistenza di soluzioni deboli e forti, le loro proprietà di unicità e regolarità, nonché il loro comportamento asintotico. La seconda parte della tesi contiene due ultimi contributi sui modelli stocastici ad interfaccia diffusa. Poiché la letteratura sull'argomento è ancora nelle prime fasi di sviluppo, problemi fondamentali come esistenza e unicità di soluzioni sono aperti anche per modelli la cui versione deterministica è ampiamente compresa. Nel Capitolo 6 viene analizzato un sistema stocastico accoppiato di tipo Navier-Stokes-Allen-Cahn. Tale modello può essere considerato un rilassamento del secondo ordine di uno dei modelli prototipici ad interfaccia diffusa, ossia il sistema di Navier-Stokes-Cahn-Hilliard. L'approccio stocastico permette, contrariamente alla controparte deterministica, di tenere conto di fenomeni non prevedibili di natura termica che avvengono alla scala microscopica. Tuttavia, i modelli stocastici non garantiscono la proprietà di conservazione della massa, che è invece una caratteristica fondamentale di alcuni sistemi fisici. Per recuperarla, è possibile regolare la scelta del rumore stocastico, rendendo però l'analisi matematica più impegnativa. L'effetto del rumore conservativo sui sistemi di Cahn-Hilliard e Allen-Cahn è oggetto del Capitolo 7.The present dissertation focuses on the mathematical analysis of several deterministic and stochastic diffuse interface models. These systems provide a significant understanding of phase separation phenomena occurring in complex materials such as binary alloys, multicomponent fluid mixtures or polymer blends. The term diffuse interface refers to the fact that the interface between two different species is modeled as a region with positive thickness. After illustrating the preliminary material in Chapters 1 and 2, the main contributions contained in this dissertation are presented in two parts: the first deals with deterministic models, while the second is devoted to stochastic ones. However, in all the models discussed, we aim to work within the physical framework. Indeed, if the energy functional of the system is thermodynamically consistent, then it is possible to show that a solution carries physical meaning (i.e., that it takes values in a physically admissible range). The main method to achieve this goal involves modeling the potential energy of the system through a function whose derivatives establish potential barriers. Indeed, this approach ensures that any solution with finite energy must be confined within them. The first part of the dissertation contains the following contributions. In Chapter 3, we examine a system for electrically responsive polymer mixtures. In particular, we are interested in blends between a diblock copolymer and a homopolymer acting as solvent. The phase separation occurring between copolymer and homopolymer, as well as the one between the two blocks of the copolymer, allows the self-assembling of ordered structures at the mesoscopic level, that also turn out to be useful in the development of nanotecnologies. In this model, Maxwellian interactions play a significant role, as the application of external electric fields is one of the primary methods to induce pattern formation. Chapter 4 illustrates, in a slightly different setting, the other side of Maxwellian interactions. Therein, we consider a model describing magnetically responsive complex fluids, accounting for hydrodynamic effects and fluid-fluid interactions. The last deterministic system, analyzed in Chapter 5, models a ternary system where two fluids are blended with a surfactant. These substances are able to reduce the interfacial tension between different fluids and allow the mixing of normally immiscible fluids (e.g., water and oil). In the aforementioned models, the recurring mathematical challenges concern the existence of weak and strong solutions, their uniqueness and regularity properties, as well as their asymptotic behavior. The second part of the dissertation contains two last contributions on stochastic diffuse interface models. As the literature on the topic is still in its early stages of development, fundamental problems as existence and uniqueness of solutions are open even for models whose deterministic version is widely understood. In Chapter 6, a coupled stochastic Navier-Stokes-Allen-Cahn system is analyzed. This can be regarded as a second-order relaxation of one of the prototypical diffuse interface models, i.e., the Navier-Stokes-Cahn-Hilliard system. The stochastic approach allows, contrary to the deterministic counterpart, to take into account unpredictable phenomena of thermal nature happening at the microscopic scale. However, stochastic models do not ensure a strong mass conservation property, which is instead a key feature of certain physical systems. In order to recover it, it is possible to fine tune the choice of the random noise, although rendering the mathematical analysis more challenging. The effect of conservative noise on the Cahn-Hilliard and the Allen-Cahn systems is the subject of Chapter 7.DIPARTIMENTO DI MATEMATICA36SABADINI, IRENE MARIACORREGGI, MICHEL

Effect of talc and chlorite on sintering and technological behaviour of porcelain stoneware tiles

The use of magnesium silicates as sintering promoters in porcelain stoneware tiles was investigated in order to understand their effect on technological properties and firing behaviour. Three formulations were designed, replacing sodic feldspar with 3% wt talc or chlorite in a reference porcelain stoneware body, and experimented at a laboratory scale simulating the industrial tilemaking cycle. The occurrence of magnesium silicates does not affect the technological properties of semi-finished products, but it influences remarkably the firing behaviour. Bodies containing talc or chlorite exhibit a faster densification kinetics, with slightly larger firing shrinkages, due to their larger amount of glassy phase, which appears to be less viscous than the reference one. On the other hand, the addition of magnesium silicates brings about a slightly lower bulk density, basically due to a larger amount of closed porosity, being water absorption negligible over 1160?C. Notwithstanding the different porosity, porcelain stoneware bodies containing talc or chlorite present just a moderate decrease of mechanical strength

Tectonic evolution of the Colorado Basin, offshore Argentina, inferred from seismo-stratigraphy and depositional rates analysis

International audienceBased on a dense 2D seismic reflection dataset and information from 8 exploration wells, we reinterpreted the stratigraphic evolution of the Colorado Basin. The basin is located on the continental shelf and slope within 50 to 2250 m of bathymetry. The total sediment fill can be up to 16,000 m. Seismic-to-well log correlations provide a chrono-stratigraphic framework for the interpreted seismic sequences. We show that the Colorado Basin records the development of a Permian pre-rift period, a Triassic/Jurassic to Early Cretaceous rift phase and a Lower Cretaceous to Tertiary drift phase. This passive margin represents the evolution of lithospheric extension from active rifting to the thermal subsidence/drift stage. Several Cretaceous to Cenozoic slumping episodes were identified and related to progradation of the sequences and sediment build-up in the slope, as well as to the development of seaward dipping extensional faults

Carotid artery stenting: a single-centre experience with up to 8 years' follow-up

Carotid artery stenting (CAS) may be an alternative to surgical endoarterectomy not only in high-risk patients. We report results in the endovascular treatment of carotid artery disease with up to 8 years' follow-up. In this retrospective study, we analysed data from 853 consecutive patients (946 arteries) treated for carotid artery stenosis between April 1999 and March 2007; 491 (52%) arteries were symptomatic and 455(48%) were asymptomatic. Preprocedural evaluation of the patients was performed with echo Doppler, magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) and a neurological examination. A cerebral protection device was used in 879 (92.9%) procedures. Anti-platelet therapy was administered before and after the procedure. All patients were included in a follow-up of up to 8 years. Technical success was achieved in 943 (99.6%) lesions. At 30 days, there was a 0.21% (n = 2) death rate, a 0.42% major stroke rate, a 1.69% minor stroke/transient ischaemic attack (TIA) rate and a combined 2.32% TIA/stroke and death rate. During follow-up, echo Doppler evidenced restenosis in 39 (4.85%) cases; of these, only five, presenting restenosis > 80%, were treated with an endovascular reintervention. At the long-term follow-up, two strokes (0.23%) were reported, which both occurred within the first 2 years. In our experience, carotid artery stenting seems to be a safe and effective treatment, providing satisfactory long-term clinical results

Colorado Basin 3D structure and evolution, Argentine passive margin

International audienceThis 3D structural model of the Colorado Basin provides new insights into the crustal geometry of the basin and its evolution in relation with the Argentine passive margin. Three NW-SE segments (oblique to the N30°E-trending margin) structure the basin. The oldest infill is generally thought to be coeval with the rifting of the South Atlantic margins in Late Jurassic-Early Cretaceous. This coeval development of the Colorado Basin and of the passive margin is still under debate and gives rise to several hypotheses that we investigate in the light of our observations. We propose that reactivation of inherited structures is predominant in the evolution of the Colorado Basin: (1) the Western segment follows the continental continuation of the Colorado transfer zone; (2) the Central segment consists in the continental continuation of the Tona deformation zone; (3) the Eastern segment is superimposed over the Palaeozoic Claromecó Basin. In addition to the 3 segments, the Central High, separating the Central segment to the Eastern segment, corresponds to the Palaeozoic Sierras Australes Fold Belt. The direction of extension responsible for the South Atlantic opening cannot explain the syn-rift infill and thinning of the basin. The structural analysis shows two phases of syn-rift deformation with different directions. Thus, we suggest that the Colorado Basin and the South Atlantic margin are not coeval but that a first extensional event, probably oblique, predates the extension responsible for the South Atlantic opening. This event is then followed by the formation of the N30°-trending distal margin and the reactivation of Palaeozoic N70°-trending faults occurs under the NW-SE opening of the South Atlantic. This two-phase evolution is consistent with the fault chronology and the two directions of thinned crust observed in the distal margin