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by Keyword: FEM


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Farré, N., Jorba, I., Torres, M., Falcones, B., Martí-Almor, J., Farré, R., Almendros, I., Navajas, D., (2018). Passive stiffness of left ventricular myocardial tissue is reduced by ovariectomy in a post-menopause mouse model Frontiers in Physiology 9, Article 1545

Background: Heart failure (HF) – a very prevalent disease with high morbidity and mortality – usually presents with diastolic dysfunction. Although post-menopause women are at increased risk of HF and diastolic dysfunction, poor attention has been paid to clinically and experimentally investigate this group of patients. Specifically, whether myocardial stiffness is affected by menopause is unknown. Aim: To investigate whether loss of female sexual hormones modifies the Young’s modulus (E) of left ventricular (LV) myocardial tissue in a mouse model of menopause induced by ovariectomy (OVX). Methods: After 6 months of bilateral OVX, eight mice were sacrificed, fresh LV myocardial strips were prepared (∼8 × 1 × 1 mm), and their passive stress–stretch relationship was measured. E was computed by exponential fitting of the stress–stretch relationship. Subsequently, to assess the relative role of cellular and extracellular matrix components in determining OVX-induced changes in E, the tissues strips were decellularized and subjected to the same stretching protocol to measure E. A control group of eight sham-OVX mice was simultaneously studied. Results: E (kPa; m ± SE) in OVX mice was ∼twofold lower than in controls (11.7 ± 1.8 and 22.1 ± 4.4, respectively; p < 0.05). No significant difference between groups was found in E of the decellularized tissue (31.4 ± 12.05 and 40.9 ± 11.5, respectively; p = 0.58). Conclusion: Loss of female sexual hormones in an OVX model induces a reduction in the passive stiffness of myocardial tissue, suggesting that active relaxation should play a counterbalancing role in diastolic dysfunction in post-menopausal women with HF.

Keywords: Decellularized tissue, Female hormones, Heart tissue, Ovariectomy, Stress-strain


Valero, C., Navarro, B., Navajas, D., García-Aznar, J. M., (2016). Finite element simulation for the mechanical characterization of soft biological materials by atomic force microscopy Journal of the Mechanical Behavior of Biomedical Materials , 62, 222-235

The characterization of the mechanical properties of soft materials has been traditionally performed through uniaxial tensile tests. Nevertheless, this method cannot be applied to certain extremely soft materials, such as biological tissues or cells that cannot be properly subjected to these tests. Alternative non-destructive tests have been designed in recent years to determine the mechanical properties of soft biological tissues. One of these techniques is based on the use of atomic force microscopy (AFM) to perform nanoindentation tests. In this work, we investigated the mechanical response of soft biological materials to nanoindentation with spherical indenters using finite element simulations. We studied the responses of three different material constitutive laws (elastic, isotropic hyperelastic and anisotropic hyperelastic) under the same process and analyzed the differences thereof. Whereas linear elastic and isotropic hyperelastic materials can be studied using an axisymmetric simplification, anisotropic hyperelastic materials require three-dimensional analyses. Moreover, we established the limiting sample size required to determine the mechanical properties of soft materials while avoiding boundary effects. Finally, we compared the results obtained by simulation with an estimate obtained from Hertz theory. Hertz theory does not distinguish between the different material constitutive laws, and thus, we proposed corrections to improve the quantitative measurement of specific material properties by nanoindentation experiments.

Keywords: AFM, Cell mechanics, FEM, Nanoindentation, Soft-tissue


Marques, J., Moles, E., Urbán, P., Prohens, R., Busquets, M. A., Sevrin, C., Grandfils, C., Fernàndez-Busquets, X., (2014). Application of heparin as a dual agent with antimalarial and liposome targeting activities toward Plasmodium-infected red blood cells Nanomedicine: Nanotechnology, Biology, and Medicine 10, (8), 1719-1728

Heparin had been demonstrated to have antimalarial activity and specific binding affinity for Plasmodium-infected red blood cells (pRBCs) vs. non-infected erythrocytes. Here we have explored if both properties could be joined into a drug delivery strategy where heparin would have a dual role as antimalarial and as a targeting element of drug-loaded nanoparticles. Confocal fluorescence and transmission electron microscopy data show that after 30. min of being added to living pRBCs fluorescein-labeled heparin colocalizes with the intracellular parasites. Heparin electrostatically adsorbed onto positively charged liposomes containing the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane and loaded with the antimalarial drug primaquine was capable of increasing three-fold the activity of encapsulated drug in Plasmodium falciparum cultures. At concentrations below those inducing anticoagulation of mouse blood in vivo, parasiticidal activity was found to be the additive result of the separate activities of free heparin as antimalarial and of liposome-bound heparin as targeting element for encapsulated primaquine. From the Clinical Editor: Malaria remains an enormous global public health concern. In this study, a novel functionalized heparin formulation used as drug delivery agent for primaquine was demonstrated to result in threefold increased drug activity in cell cultures, and in a murine model it was able to provide these benefits in concentrations below what would be required for anticoagulation. Further studies are needed determine if this approach is applicable in the human disease as well.

Keywords: Heparin, Liposomes, Malaria, Plasmodium, Targeted drug delivery, Heparin, Malaria, Plasmodium, Red blood cell, Targeted drug delivery, Liposomes, 1,2 dioleoyl 3 trimethylammoniopropane, fluorescein, heparin, liposome, nanoparticle, primaquine, adsorption, animal experiment, anticoagulation, antimalarial activity, Article, binding affinity, confocal microscopy, controlled study, drug targeting, encapsulation, erythrocyte, female, fluorescence microscopy, human, human cell, in vivo study, liposomal delivery, mouse, nonhuman, Plasmodium falciparum, transmission electron microscopy


Melo, E., Cárdenes, N., Garreta, E., Luque, T., Rojas, M., Navajas, D., Farré, R., (2014). Inhomogeneity of local stiffness in the extracellular matrix scaffold of fibrotic mouse lungs Journal of the Mechanical Behavior of Biomedical Materials , 37, 186-195

Lung disease models are useful to study how cell engraftment, proliferation and differentiation are modulated in lung bioengineering. The aim of this work was to characterize the local stiffness of decellularized lungs in aged and fibrotic mice. Mice (2- and 24-month old; 14 of each) with lung fibrosis (N=20) and healthy controls (N=8) were euthanized after 11 days of intratracheal bleomycin (fibrosis) or saline (controls) infusion. The lungs were excised, decellularized by a conventional detergent-based (sodium-dodecyl sulfate) procedure and slices of the acellular lungs were prepared to measure the local stiffness by means of atomic force microscopy. The local stiffness of the different sites in acellular fibrotic lungs was very inhomogeneous within the lung and increased according to the degree of the structural fibrotic lesion. Local stiffness of the acellular lungs did not show statistically significant differences caused by age. The group of mice most affected by fibrosis exhibited local stiffness that were ~2-fold higher than in the control mice: from 27.2±1.64 to 64.8±7.1. kPa in the alveolar septa, from 56.6±4.6 to 99.9±11.7. kPa in the visceral pleura, from 41.1±8.0 to 105.2±13.6. kPa in the tunica adventitia, and from 79.3±7.2 to 146.6±28.8. kPa in the tunica intima. Since acellular lungs from mice with bleomycin-induced fibrosis present considerable micromechanical inhomogeneity, this model can be a useful tool to better investigate how different degrees of extracellular matrix lesion modulate cell fate in the process of organ bioengineering from decellularized lungs.

Keywords: Ageing, Atomic force microscopy, Decellularization, Lung fibrosis, Tissue engineering, Atomic force microscopy, Biological organs, Peptides, Sodium dodecyl sulfate, Sodium sulfate, Tissue engineering, Ageing, Decellularization, Extracellular matrices, Healthy controls, Inhomogeneities, Lung fibrosis, Micro-mechanical, Statistically significant difference, Mammals, bleomycin, adventitia, animal experiment, animal model, article, atomic force microscopy, bleomycin-induced pulmonary fibrosis, cell fate, controlled study, extracellular matrix, female, intima, lung alveolus, lung fibrosis, lung mechanics, mechanical probe, microenvironment, mouse, nonhuman, pleura, priority journal, rigidity, tissue engineering


Nonaka, P. N., Uriarte, J. J., Campillo, N., Melo, E., Navajas, D., Farré, R., Oliveira, L. V. F., (2014). Mechanical properties of mouse lungs along organ decellularization by sodium dodecyl sulfate Respiratory Physiology & Neurobiology , 200, 1-5

Lung decellularization is based on the use of physical, chemical, or enzymatic methods to break down the integrity of the cells followed by a treatment to extract the cellular material from the lung scaffold. The aim of this study was to characterize the mechanical changes throughout the different steps of lung decellularization process. Four lungs from mice (C57BL/6) were decellularized by using a conventional protocol based on sodium dodecyl sulfate. Lungs resistance (RL) and elastance (EL) were measured along decellularization steps and were computed by linear regression fitting of tracheal pressure, flow, and volume during mechanical ventilation. Transients differences found were more distinct in an intermediate step after the lungs were rinsed with deionized water and treated with 1% SDS, whereupon the percentage of variation reached approximately 80% for resistance values and 30% for elastance values. In conclusion, although a variation in extracellular matrix stiffness was observed during the decellularization process, this variation can be considered negligible overall because the resistance and elastance returned to basal values at the final decellularization step.

Keywords: Lung bioengineering, Lung decellularization, Organ scaffold, dodecyl sulfate sodium, animal tissue, article, artificial ventilation, compliance (physical), controlled study, enzyme chemistry, extracellular matrix, female, flow, lung, lung decellularization, lung pressure, lung resistance, mouse, nonhuman, positive end expiratory pressure, priority journal, rigidity, tissue engineering, trachea pressure


Sánchez Egea, Antonio J., Valera, Marius, Parraga Quiroga, Juan Manuel, Proubasta, Ignasi, Noailly, J., Lacroix, Damien, (2014). Impact of hip anatomical variations on the cartilage stress: A finite element analysis towards the biomechanical exploration of the factors that may explain primary hip arthritis in morphologically normal subjects Clinical Biomechanics , 29, (4), 444-450

AbstractBackground Hip arthritis is a pathology linked to hip-cartilage degeneration. Although the aetiology of this disease is not well defined, it is known that age is a determinant risk factor. However, hip arthritis in young patients could be largely promoted by biomechanical factors. The objective of this paper is to analyze the impact of some normal anatomical variations on the cartilage stress distributions numerically predicted at the hip joint during walking. Methods A three-dimensional finite element model of the femur and the pelvis with the most relevant axial components of muscle forces was used to simulate normal walking activity. The hip anatomical condition was defined by: neck shaft angle, femoral anteversion angle, and acetabular anteversion angle with a range of 110-130º, 0-20º, and 0-20º, respectively. The direct boundary method was used to simulate the hip contact. Findings The hydrostatic stress found at the cartilage and labrum showed that a ± 10º variation with respect to the reference brings significant differences between the anatomic models. Acetabular anteversion angle of 0º and femoral anteversion angle of 0º were the most affected anatomical conditions with values of hydrostatic stress in the cartilage near 5 MPa under compression. Interpretation Cartilage stresses and contact areas were equivalent to the results found in literature and the most critical anatomical regions in terms of tissue loads were in a good accordance with clinical evidence. Altogether, results showed that decreasing femoral or acetabular anteversion angles isolately causes a dramatic increase in cartilage loads.

Keywords: Hip arthritis, Neck shaft angle, Femoral and acetabular anteversions, Cartilage load, Hip joint contact, Finite element analysis


Fonollosa, J., Carmona, M., Santander, J., Fonseca, L., Moreno, M., Marco, S., (2009). Limits to the integration of filters and lenses on thermoelectric IR detectors by flip-chip techniques Sensors and Actuators A: Physical , 149, (1), 65-73

In the trend towards miniaturization, a detector module containing multiple IR sensor channels is being built and characterized. In its final form it contains thermopiles, narrow band filters and Fresnel lenses. An important feature of such module is the assembly by flip-chip of the IR filters on top of the thermopiles. The performance of the filter-thermopile ensemble has been assessed by physical simulation and experiments and it has been optimized by the use of an empirically validated model. It has been found that integration of filters (or lenses) too close to the IR detector may lead to degraded performance due to thermal coupling. The impact and extent of this degradation has been thoroughly explored, being the main parameter the distance between the IR sensor and the filter. To avoid such detrimental effects a possibility is to set the device in vacuum conditions, obtaining an improved output response and avoiding the influence of the filters. Another way is to increase the solder joint height. Beyond a certain height, the filter is considered to be isolated from the thermopile.

Keywords: Assembly, Infrared sensor, Infrared filter, Fresnel lenses, FEM simulation, Optimization


Udina, S., Carmona, M., Carles, G., Santander, J., Fonseca, L., Marco, S., (2008). A micromachined thermoelectric sensor for natural gas analysis: Thermal model and experimental results Sensors and Actuators B: Chemical 134, (2), 551-558

Natural gas may show significant changes in its chemical composition depending on its origin. Typically, natural gas analysis is carried out using process gas chromatography. However, other methods based on the evaluation of physical properties have recently been reported. Thermal conductivity sensors are currently used in the analysis of binary mixtures of dissimilar gases. In contrast, natural gas is a complex mixture of mainly hydrocarbons, plus other residual gases as carbon dioxide and nitrogen. In this work, the response of a micromachined sensor integrating a heater and a thermopile is studied, regarding its potential use for natural gas analysis. A finite element thermal model of the device is described, and thermal operation simulations as well as a preliminary sensitivity analysis are reported. Experimental data has been collected and compared with simulated data, showing very good agreement. Results show that small variations in the gas mixture composition can be clearly detected. The sensor appears as a good candidate to be included in low-cost natural gas property analysis and quality control systems.

Keywords: Natural gas, Thermopile, MEMS, Thermal conductivity, Modeling, FEM simulation


Diez, Pablo F., Laciar, Eric, Mut, Vicente, Avila, Enrique, Torres, Abel, (2008). A comparative study of the performance of different spectral estimation methods for classification of mental tasks IEEE Engineering in Medicine and Biology Society Conference Proceedings 30th Annual International Conference of the Ieee Engineering in Medicine and Biology Society (ed. IEEE), IEEE (Vancouver, Canada) 1-8, 1155-1158

In this paper we compare three different spectral estimation techniques for the classification of mental tasks. These techniques are the standard periodogram, the Welch periodogram and the Burg method, applied to electroencephalographic (EEG) signals. For each one of these methods we compute two parameters: the mean power and the root mean square (RMS), in various frequency bands. The classification of the mental tasks was conducted with a linear discriminate analysis. The Welch periodogram and the Burg method performed better than the standard periodogram. The use of the RMS allows better classification accuracy than the obtained with the power of EEG signals.

Keywords: Adult, Algorithms, Artificial Intelligence, Cognition, Electroencephalography, Female, Humans, Male, Pattern Recognition, Automated, Reproducibility of Results, Sensitivity and Specificity, Task Performance and Analysis, User-Computer Interface