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In this study, the influence of a plasma electrolytic oxidation (PEO) surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion features and mechanical properties throughout the corrosion process. First, a comprehensive in-vitro immersion study was performed on WE43-based tensile specimens with and without PEO surface modification, which included fully automated spatial reconstruction of the phenomenological features of corrosion through micro-CT scanning, followed by uniaxial tensile testing. Then the experimental data of both unmodified and PEO-modified groups were used to calibrate parameters of a finite element-based surface corrosion model. In-vitro, it was found that the WE43-PEO modified group had a significantly lower corrosion rate and maintained significantly higher mechanical properties than the unmodified. While corrosion rates were â¼50% lower in the WE43-PEO modified specimens, the local geometric features of corroding surfaces remained similar to the unmodified WE43 group, however evolving after almost the double amount of time. We were also able to quantitatively demonstrate that the PEO surface treatment on magnesium continued to protect samples from corrosion throughout the entire period tested, and not just in the early stages of corrosion. Using the results from the testing framework, the model parameters of the surface-based corrosion model were identified for both groups. This enabled, for the first time, in-silico prediction of the physical features of corrosion and the mechanical performance of both unmodified and PEO modified magnesium specimens. This simulation framework can enable future in-silico design and optimisation of bioabsorbable magnesium devices for load-bearing medical applications.
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This study developed an enhanced phenomenological model for the predictions of surface-based localised corrosion of magnesium alloys for use in medical applications. The modelling framework extended previous surface-based approaches by considering the role of ß-phase components throughout the material volume to better predict spatial and temporal aspects of surface-based corrosion in magnesium alloys. This enhanced surface-based corrosion model offers many advantages as it (i) captures multi-directional pitting, (ii) captures various pit morphologies, (iii) eliminates mesh sizing effects, (iv) reduces computational cost through custom time controls (v) offers control of pit sizing and (vi) produces corrosion rates that are independent of pitting parameter values. The model was fully implemented in three dimensions within the finite element framework and shows excellent potential to enable robust predictions of the long-term performance of magnesium-based implants undergoing corrosion.
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Aleaciones , Magnesio , Corrosión , Implantes Absorbibles , Ensayo de MaterialesRESUMEN
This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework PitScan provides detailed quantification of the spatial phenomenological features of corrosion, including a full geometric tracking of corroding surface. Through this approach, this study is the first to quantitatively demonstrate that a surface-based non-uniform corrosion model can capture both the geometrical and mechanical features of a magnesium alloy undergoing corrosion by comparing to experimental data. Using this verified corrosion modelling approach, a wide range of corrosion scenarios was evaluated and enabled quantitative relationships to be established between the mechanical integrity and key phenomenological corrosion features. In particular, we demonstrated that the minimal cross-sectional area parameter was the strongest predictor of the remaining mechanical strength (R2 = 0.98), with this relationship being independent of the severity or spatial features of localised surface corrosion. Interestingly, our analysis demonstrated that parameters described in ASTM G46-94 showed weaker correlations to the mechanical integrity of corroding specimens, compared to parameters determined by Pitscan. This study establishes new mechanistic insight into the performance of the magnesium-based materials undergoing corrosion.
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Issues with current treatments for osteochondral defects such as mosaicplasty and autologous chondrocyte implantation (ACI) are lack of donor material, problems associated with donor sites, necessity of second surgical intervention and cell expansion, difficult site preparation and implant fitting to match the surrounding tissue. This study presents the development of a patient specific implant system for focal osteochondral defects that addresses these issues. Using computer aided design and manufacturing techniques, computed tomography scans are utilized to design the implant and templates that facilitate site preparation to allow for precise and easy implantation of the designed perfectly fitting tissue replacement. Functionality of the system and accurate restoration of a defect is demonstrated by digital before/after comparison and with a prototype. With the presented implantation system larger defects in curved joint surfaces can be restored to an optimal shape in an easier procedure than for instance mosaicplasty. The proposed system potentially allows for later replacement of worn implants.
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This study develops a three-dimensional automated detection framework (PitScan) that systematically evaluates the severity and phenomenology of pitting corrosion. This framework uses a python-based algorithm to analyse microcomputer-tomography scans (µCT) of cylindrical specimens undergoing corrosion. The approach systematically identifies several surface-based corrosion features, enabling full spatial characterisation of pitting parameters, including pit density, pit size, pit depth as well as pitting factor according to ASTM G46-94. Furthermore, it is used to evaluate pitting formation in tensile specimens of a Rare Earth Magnesium alloy undergoing corrosion, and relationships between key pitting parameters and mechanical performance are established. Results demonstrated that several of the parameters described in ASTM G46-94, including pit number, pit density and pitting factor, showed little correlation to mechanical performance. However, this study did identify that other parameters showed strong correlations with the ultimate tensile strength and these tended to be directly linked to the reduction of the cross-sectional area of the specimen. Specifically, our results indicate, that parameters directly linked to the loss of the cross-sectional area (e.g. minimum material width), are parameters that are most suited to provide an indication of a specimen's mechanical performance. The automated detection framework developed in this study has the potential to provide a basis to standardise measurements of pitting corrosion across a range of metals and future prediction of mechanical strength over degradation time.
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With mechanical thrombectomy emerging as the new standard of care for stroke treatment, clot analogues provide an extremely useful tool in the testing and design of these treatment devices. The aim of this study is to characterise the mechanical behavior of thrombus analogues as a function of composition. Platelet-contracted clot analogues were prepared from blood mixtures of various hematocrits. Mechanical testing was performed whereby clots were subjected to unconfined compression between two rigid plates. Two loading protocols were imposed: cyclic compression for 10 cycles at a constant strain-rate magnitude; stress-relaxation at a constant applied compressive strain. A hyper-viscoelastic constitutive law was identified and calibrated based on the experimental mechanical test data. Scanning electron microscopy (SEM) investigated the clot microstructure at various time-points. Clot analogue composition was found to strongly affect the observed mechanical behavior. The SEM found that the microstructure of the clot analogues was affected by the storage solution and age of the clot. The proposed hyper-viscoelastic constitutive model was found to successfully capture the material test data. The results presented in this study are of key importance to the evaluation and future development mechanical thrombectomy devices and procedures.
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Trombosis/fisiopatología , Animales , Fenómenos Biomecánicos , Microscopía Electrónica de Rastreo , Modelos Biológicos , Ovinos , Estrés MecánicoRESUMEN
An enhanced understanding of the structure and mechanical behavior of atherosclerotic plaque can potentially provide key guidance for clinical intervention and vascular device design. This study presents an investigation of morphological and mechanical properties of iliofemoral (n = 8) and carotid (n = 22) atherosclerotic plaque constituents. µCT analysis is used characterize the content and morphology of calcifications in excised plaques. Calcified particles contribute a significant proportion of the average plaque volume (7.6% carotid; 19.1% iliofemoral), and on average over 50% of this volume (53.7 ± 18.6% carotid; 61.7 ± 15% iliofemoral) is accounted for by the largest individual particle found in the plaque. Fibrous tissue and calcifications were isolated for mechanical testing. Unconfined compression testing of isolated calcifications uncovered viscoelastic behavior. Tensile stress relaxation uncovered viscoelastic behavior in fibrous atherosclerotic samples. Iliofemoral fibrous samples were found to be statistically significantly stiffer (*p < 0.05) than carotid fibrous samples. Results show isolated calcifications are approximately two orders of magnitude stiffer than non-calcified fibrous tissue. The results from this study advance the current understanding of plaque mechanics and suggest that computational simulation of angioplasty procedures should incorporate a discrete representation of atherosclerotic plaque constituents.
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Aterosclerosis , Calcinosis , Placa Aterosclerótica , Arterias Carótidas/diagnóstico por imagen , Simulación por Computador , HumanosRESUMEN
: â BACKGROUND: Calcified cerebral emboli (CCEs) are a rare cause of acute ischemic stroke (AIS) and are frequently associated with poor outcomes. The presence of dense calcified material enables reliable identification of CCEs using non-contrast CT. However, recanalization rates with the available mechanical thrombectomy (MT) devices remain low. OBJECTIVE: To recreate a large vessel occlusion involving a CCE using an in vitro silicone model of the intracranial vessels and to demonstrate the feasability of this model to test different endovascular strategies to recanalize an occlusion of the M1 segment of the middle cerebral artery (MCA). : â METHODS: An in vitro model was developed to evaluate different endovascular treatment approaches using contemporary devices in the M1 segment of the MCA. The in vitro model consisted of a CCE analog placed in a silicone neurovascular model. Development of an appropriate CCE analog was based on characterization of human calcified tissues that represent likely sources of CCEs. Feasibility of the model was demonstrated in a small number of MT devices using four common procedural techniques. : â RESULTS: CCE analogs were developed with similar mechanical behavior to that of ex vivo calcified material. The in vitro model was evaluated with various MT techniques and devices to show feasibility of the model. In this limited evaluation, the most successful retrieval approach was performed with a stent retriever combined with local aspiration through a distal access catheter, and importantly, with flow arrest and dual aspiration using a balloon guide catheter. : â CONCLUSION: Characterization of calcified tissues, which are likely sources of CCEs, has shown that CCEs are considerably stiffer than thrombus. This highlights the need for a different in vitro AIS model for CCEs than those used for thromboemboli. Consequentially, an in vitro AIS model representative of a CCE occlusion in the M1 segment of the MCA has been developed.
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Isquemia Encefálica/diagnóstico por imagen , Embolia Intracraneal/diagnóstico por imagen , Modelos Anatómicos , Accidente Cerebrovascular/diagnóstico por imagen , Trombectomía/métodos , Calcificación Vascular/diagnóstico por imagen , Anciano , Animales , Isquemia Encefálica/terapia , Femenino , Humanos , Embolia Intracraneal/terapia , Masculino , Ovinos , Accidente Cerebrovascular/terapia , Trombectomía/normas , Resultado del Tratamiento , Calcificación Vascular/terapia , Microtomografía por Rayos X/métodosRESUMEN
BACKGROUND: Clot mechanical properties are influenced by composition and the arrangement of components within the clot. This work investigates the effects of platelet-driven contraction on blood clot microstructure and mechanical behavior, and provides insight into some implications for mechanical thrombectomy. METHODS: Platelet-contracted clot analogues (PCCs) and non-contracted clot analogues (NCCs) were prepared from blood mixtures of various hematocrits (%H), that is, the volume percentage of red blood cells (RBCs) in the mixture. Mechanical testing was performed to compare the behavior of the analogues with previously tested human thromboemboli. Scanning electron microscopy and histology investigated the clot microstructure and composition. The association between clot properties and their behavior during mechanical behavior was also investigated. RESULTS: Overall, PCCs were found to be stiffer than NCCs, across all hematocrits. PCCs with a low %H resisted complete ingestion via contact aspiration alone or complete retrieval with stent-retrievers. PCCs with a higher %H and all NCCs were fully retrievable, although the likelihood of fragmentation was increased in clots with a greater %H. Histologically, there was little difference in the RBC and fibrin content between PCCs and NCCs with the same %H. However, the microstructure of the two groups differed significantly. CONCLUSION: A selection of repeatable clot analogues with a range of mechanical properties have been developed for in vitro modeling of acute ischemic stroke. Platelet contraction significantly affects clot volume and microstructure, and in turn clot stiffness. The significant difference in mechanical properties and microstructure, but without an appreciable difference in histology, implies that histological studies of explanted human clots alone may not prove to be predictive of the mechanical behavior of the clots in thrombectomy.
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Fenómenos Biomecánicos/fisiología , Trombectomía/métodos , Trombosis/patología , Trombosis/fisiopatología , Animales , Isquemia Encefálica/patología , Isquemia Encefálica/terapia , Eritrocitos/patología , Eritrocitos/fisiología , Humanos , Microscopía Electrónica de Rastreo/métodos , Ovinos , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/terapiaRESUMEN
Braided stents are associated with a number of complications in vivo. Accurate computational modelling of these devices is essential for the design and development of the next generation of these stents. In this study, two commonly utilised methods of computationally modelling filament interaction in braided stents are investigated: the join method and the weave method. Three different braided stent designs are experimentally tested and computationally modelled in both radial and v-block configurations. The results of the study indicate that while both methods are capable of capturing braided stent performance to some degree, the weave method is much more robust.
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Simulación por Computador , Modelos Teóricos , Stents , Aleaciones/química , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Estrés MecánicoRESUMEN
Significant research has been conducted in the area of coronary stents/scaffolds made from resorbable metallic and polymeric biomaterials. These next-generation bioabsorbable stents have the potential to completely revolutionise the treatment of coronary artery disease. The primary advantage of resorbable devices over permanent stents is their temporary presence which, from a theoretical point of view, means only a healed coronary artery will be left behind following degradation of the stent potentially eliminating long-term clinical problems associated with permanent stents. The healing of the artery following coronary stent/scaffold implantation is crucial for the long-term safety of these devices. Computational modelling can be used to evaluate the performance of complex stent devices in silico and assist in the design and development and understanding of the next-generation resorbable stents. What is lacking in computational modelling literature is the representation of the active response of the arterial tissue in the weeks and months following stent implantation, ie, neointimal remodelling, in particular for the case of biodegradable stents. In this paper, a computational modelling framework is developed, which accounts for two major physiological stimuli responsible for neointimal remodelling and combined with a magnesium corrosion model that is capable of simulating localised pitting (realistic) stent corrosion. The framework is used to simulate different neointimal growth patterns and to explore the effects the neointimal remodelling has on the mechanical performance (scaffolding support) of the bioabsorbable magnesium stent.
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Magnesio/química , Stents , Materiales Biocompatibles , Análisis de Elementos Finitos , Humanos , NeointimaRESUMEN
Lung cancer patients often suffer from severe airway stenosis, the symptoms of which can be relieved by the implantation of stents. Different respiratory stents are commercially available, but the impact of their mechanical performance on tissue responses is not well understood. Two novel laser-cut and hand-braided nitinol stents, partially covered with polycarbonate urethane, were bench tested and implanted in Rhön sheep for 6 weeks. Bench testing highlighted differences in mechanical behavior: the laser-cut stent showed little foreshortening when crimped to a target diameter of 7.5 mm, whereas the braided stent elongated by more than 50%. Testing also revealed that the laser-cut stent generally exerted higher radial resistive and chronic outward forces than the braided stent, but the latter produced significantly higher radial resistive forces at diameters below 9 mm. No migration was observed for either stent type in vivo. In terms of granulation, most stents exerted a low to medium tissue response with only minimal formation of granulation tissue. We have developed a mechanical and in vivo framework to compare the behavior of different stent designs in a large animal model, providing data, which may be employed to improve current stent designs and to achieve better treatment options for lung cancer patients.
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Diseño de Prótesis , Stents , Aleaciones , Animales , Femenino , Rayos Láser , Ensayo de Materiales , OvinosRESUMEN
BACKGROUND: Although it is common practice to wait for an 'embedding time' during mechanical thrombectomy (MT) to allow strut integration of a stentriever device into an occluding thromboembolic clot, there is a scarcity of evidence demonstrating the value or optimal timing for the wide range of thrombus compositions. This work characterizes the behavior of clot analogs of varying fibrin and cellular compositions subject to indentation forces and embedding times representative of those imparted by a stentriever during MT. The purpose of this study is to quantify the effect of thrombus composition on device strut embedding, and to examine the precise nature of clot integration into a stentriever device at a microstructural level. METHOD: Clot analogs with 0% (varying densities), 5%, 40%, and 80% red blood cell (RBC) content were created using ovine blood. Clot indentation behavior during an initial load application (loading phase) followed by a 5-min embedding time (creep phase) was analyzed using a mechanical tester under physiologically relevant conditions. The mechanism of strut integration was examined using micro-computed tomography (µCT) with an EmboTrap MT device (Cerenovus, Galway, Ireland) deployed in each clot type. Microstructural clot characteristics were identified using scanning electron microscopy (SEM). RESULTS: Compressive clot stiffness measured during the initial loading phase was shown to be lowest in RBC-rich clots, with a corresponding greatest maximum indentation depth. Meanwhile, additional depth achieved during the simulated embedding time was most pronounced in fibrin-rich clots. SEM imaging identified variations in microstructural mechanisms (fibrin stretching vs rupturing) which was dependent on fibrin:cellular content, while µCT analysis demonstrated the mechanism of strut integration was predominantly the formation of surface undulations rather than clot penetration. CONCLUSIONS: Disparities in indentation behavior between clot analogs were attributed to varying microstructural features induced by the cellular:fibrin content. Greater indentation was identified in clots with higher RBC content, but with an increased level of fibrin rupture, suggesting an increased propensity for fragmentation. Additional embedding time improves strut integration, especially in fibrin-rich clots, through the mechanism of fibrin stretching with the majority of additional integration occurring after 3 mins. The level of thrombus incorporation into the EmboTrap MT device (Cerenovus, Galway, Ireland) was primarily influenced by the stentriever design, with increased integration in regions of open architecture.
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Isquemia Encefálica/patología , Eritrocitos/patología , Accidente Cerebrovascular/patología , Trombosis/patología , Animales , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Eritrocitos/química , Eritrocitos/ultraestructura , Femenino , Fibrina/química , Irlanda , Masculino , Microscopía Electrónica de Rastreo/métodos , Prótesis e Implantes , Ovinos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Tromboembolia/diagnóstico por imagen , Tromboembolia/patología , Tromboembolia/cirugía , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Microtomografía por Rayos X/métodosRESUMEN
The purpose of the present study was to develop gefitinib-loaded polymeric foams that can be used as coating of drug-eluting stents for palliative treatment of bronchotracheal cancer. Release of such an anticancer drug from such stent coating can retard tumor regrowth into the bronchial lumen. Gefitinib-loaded polyurethane (PU) foams were prepared by embedding either gefitinib micronized crystals or gefitinib-loaded poly(lactic-co-glycolic acid) microspheres in water-blown films, with up to 10% w/w loading for gefitinib microcrystals and 15% w/w for gefitinib microspheres (corresponding to 1.0% w/w drug loading). Drug-release studies showed sustained release of gefitinib over a period of nine months, with higher absolute release rates at higher drug loading content. By the end of the studied nine month release periods, 60-100% of the loaded gefitinib had been released. Foams loaded with gefitinib-PLGA microspheres at 15% w/w showed accelerated drug release after 4 months, coinciding with the degradation of PLGA microparticles in the PU foam as demonstrated by scanning electron microscopy (SEM). When applied on a nitinol braided bronchotrachial stent, PU coatings with gefitinib microspheres showed similar mechanical properties as the drug-free PU coating, which indicated that the loading of microspheres did not affect the mechnical properties of the PU foams. In conclusion, we have fabricated drug-loaded PU foams that are suitable for bronchotracheal stent coating.
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Antineoplásicos/farmacocinética , Neoplasias de los Bronquios , Stents Liberadores de Fármacos , Gefitinib/farmacocinética , Poliuretanos/farmacocinética , Neoplasias de la Tráquea , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Neoplasias de los Bronquios/tratamiento farmacológico , Neoplasias de los Bronquios/metabolismo , Liberación de Fármacos , Gefitinib/administración & dosificación , Gefitinib/química , Poliuretanos/administración & dosificación , Poliuretanos/química , Neoplasias de la Tráquea/tratamiento farmacológico , Neoplasias de la Tráquea/metabolismo , Difracción de Rayos X/métodosRESUMEN
The clinical translation of regenerative therapy for the diseased heart, whether in the form of cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses. Here, we report the development and application of a therapeutic epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium via a polymer-based reservoir connected to a subcutaneous port. In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the epicardial reservoir provided functional benefits in ejection fraction, fractional shortening and stroke work, compared to a single injection of cells and to no treatment. The pre-clinical use of the therapeutic epicardial reservoir as a research model may enable insights into regenerative cardiac therapy, and assist the development of experimental therapies towards clinical use.
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Tratamiento Basado en Trasplante de Células y Tejidos/instrumentación , Pericardio , Prótesis e Implantes , Medicina Regenerativa/instrumentación , Animales , Células Cultivadas , Diseño de Equipo , Femenino , Infarto del Miocardio/terapia , Pericardio/fisiología , Pericardio/cirugía , Ratas , Ratas Sprague-DawleyRESUMEN
Tracheobronchial stents are used to restore patency to stenosed airways. However, these devices are associated with many complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. Of these, granulation tissue formation is the complication that most frequently requires costly secondary interventions. In this study a biomechanical lung modelling framework recently developed by the authors to capture the lung in-vivo stress state under physiological loading is employed in conjunction with ovine pre-clinical stenting results and device experimental data to evaluate the effect of stent interaction on granulation tissue formation. Stenting is simulated using a validated model of a prototype covered laser-cut tracheobronchial stent in a semi-specific biomechanical lung model, and physiological loading is performed. Two computational methods are then used to predict possible granulation tissue formation: the standard method which utilises the increase in maximum principal stress change, and a newly proposed method which compares the change in contact pressure over a respiratory cycle. These computational predictions of granulation tissue formation are then compared to pre-clinical stenting observations after a 6-week implantation period. Experimental results of the pre-clinical stent implantation showed signs of granulation tissue formation both proximally and distally, with a greater proximal reaction. The standard method failed to show a correlation with the experimental results. However, the contact change method showed an apparent correlation with granulation tissue formation. These results suggest that this new method could be used as a tool to improve future device designs.
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Bronquios/fisiología , Stents , Tráquea/fisiología , Aleaciones/farmacología , Animales , Bronquios/diagnóstico por imagen , Simulación por Computador , Femenino , Modelos Animales , Presión , Ovinos , Estrés Mecánico , Tomografía Computarizada por Rayos X , Tráquea/diagnóstico por imagenRESUMEN
The desire to overcome the limitations of cardiovascular metal stents is driven by the global clinical need to improve patient outcomes. The opportunity for fully polymeric stents made from materials like Poly-L-lactide Acid (PLLA) is significant. Unfortunately, this potential has not been fully realised due to pressing concerns regarding the radial strength and recoil associated with material stiffness and recoverability. In an effort to achieve effective and reliable performance, it is conceivable that a certain degree of shape memory effect (SME) could be beneficial in order to improve on high recoil associated with fully polymeric stents. In this paper, a computational model is presented to explore this possibility, using a stent geometry based on that of a commercially available polymeric stent (Abbott Absorb). The model predicts improvements in the recoil behaviour if the stent is subjected to temperature changes (introducing the shape memory effect to the material) prior to implantation compared to balloon inflation alone. The analysis indicates that combination of self-expansion and balloon inflation is capable of reducing stent recoil to a desirable level (5%). Additionally, the analysis suggests that the recoil is not strongly related to expansion rate variation. However, the stent expansion rate is critically linked to the maximum stresses in the material, with significantly higher stresses found if the stent was deployed with a higher rate, leading to a significantly higher material failure risk. It is concluded that the model provides new insights that can guide the development of fully polymeric stents towards optimised clinical performance with the potential to improve patient outcomes.
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Angioplastia de Balón/instrumentación , Modelos Cardiovasculares , Poliésteres/química , Stents , Simulación por Computador , Diseño Asistido por Computadora , Elasticidad , Análisis de Elementos Finitos , Diseño de Prótesis , ViscosidadRESUMEN
Tracheobronchial stents are most commonly used to restore patency to airways stenosed by tumour growth. Currently all tracheobronchial stents are associated with complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. The present work develops a computational framework to evaluate tracheobronchial stent designs in vivo. Pressurised computed tomography is used to create a biomechanical lung model which takes into account the in vivo stress state, global lung deformation and local loading from pressure variation. Stent interaction with the airway is then evaluated for a number of loading conditions including normal breathing, coughing and ventilation. Results of the analysis indicate that three of the major complications associated with tracheobronchial stents can potentially be analysed with this framework, which can be readily applied to the human case. Airway deformation caused by lung motion is shown to have a significant effect on stent mechanical performance, including implications for stent migration, granulation formation and stent fracture.
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Bronquios/fisiología , Stents , Tráquea/fisiología , Aleaciones/farmacología , Animales , Bronquios/diagnóstico por imagen , Simulación por Computador , Capacidad Residual Funcional , Imagenología Tridimensional , Presión , Ovinos , Estrés Mecánico , Tomografía Computarizada por Rayos X , Capacidad Pulmonar Total , Tráquea/diagnóstico por imagenRESUMEN
One of the complications of bronchotracheal cancer is obstruction of the upper airways. Local tumor resection in combination with an airway stent can suppress intraluminal tumor (re)growth. We have investigated a novel drug-eluting stent coating for local release of the anticancer drug gefitinib. A polyurethane (PU) sandwich construct was prepared by a spray coating method in which gefitinib was embedded between a PU support layer of 200µm and a PU top layer of 50-200µm. Gefitinib was either embedded in the construct as small crystals or as gefitinib-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSP). The drug was incorporated in the PU constructs with high recovery (83-93%), and the spray coating procedure did not affect the morphologies of the embedded microspheres as demonstrated by scanning electron microscopy (SEM), confocal laser scanning microscopy and fluorescence microscopy analysis. PU constructs loaded with gefitinib crystals released the drug for 7-21days and showed diffusion based release kinetics. Importantly, directional release of the drug towards the top layer, which is supposed to face the tumor mass, was controlled by the thicknesses of the PU top layer. PU constructs loaded with gefitinib microspheres released the drug in a sustained manner for >6months indicating that drug release from the microspheres became the rate limiting step. In conclusion, the sandwich structure of drug-loaded PLGA microspheres in PU coating is a promising coating for airway stents that release anticancer drugs locally for a prolonged time.
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Stents Liberadores de Fármacos , Ácido Láctico/química , Ácido Poliglicólico/química , Poliuretanos/química , Quinazolinas/química , Preparaciones de Acción Retardada , Liberación de Fármacos , Excipientes/química , Gefitinib , Humanos , Microesferas , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
Currently, there is no optimal treatment available for end stage tumour patients with airway stenosis. The PulmoStent concept aims on overcoming current hurdles in airway stenting by combining a nitinol stent with a nutrient-permeable membrane, which prevents tumour ingrowth. Respiratory epithelial cells can be seeded onto the cover to restore mucociliary clearance. In this study, a novel hand-braided dog bone stent was developed, covered with a polycarbonate urethane nonwoven and mechanically tested. Design and manufacturing of stent and cover were improved in an iterative process according to predefined requirements for permeability and mechanical properties and finally tested in a proof of concept animal study in sheep for up to 24 weeks. In each animal two stents were implanted, one of which was cell-seeded by endoscopic spraying in situ. We demonstrated the suitability of this membrane for our concept by glucose transport testing and in vitro culture of respiratory epithelial cells. In the animal study, no migration occurred in any of the twelve stents. There was only mild granulation tissue formation and tissue reaction; no severe mucus plugging was observed. Thus, the PulmoStent concept might be a step forward for palliative treatment of airway stenosis with a biohybrid stent device.