Caractérisation mécanique et microstructurale du comportement à rupture de la capsule de Glisson pour la prédiction du risque de lésions des tissus hépatiques humains

Customized human body models offer a great potential to assess the injury risks in the fields of transport safety, surgery or sport. Various detail levels can then be needed, according to the targeted application. In particular, when the mechanical behavior of biological tissues needs to be accurately reproduced, numerical models have to include information about the structure of the tissue, and model the mechanisms of the response to mechanical loading. The work presented here focuses on the microstructural and mechanical characterization of the human liver capsule, in order to identify the important hypotheses that need to be included in a fibrous tissue constitutive model, based on microstructure. Thus, an experimental methodology has been developed to identify the mechanical behavior of this particular tissue, related with its microstructural organization. Uniaxial tensile tests, as well as bulge tests under a multiphoton confocal microscope have been performed, to observe the microstructure evolution during loading. Macroscopic strain has been assessed, and a method to measure local strain fields has been developed, to quantify the strain state of the fibrous network. The reorganization of the collagen fibers network has also been quantified. An analysis of the links between the measured macroscopic parameters and the microscopic phenomena is given. Therefore, the hypotheses that need to be included in constitutive models are highlighted, with particular consideration given to the affine transformation hypothesis which allows to link the fibers behavior to the global response of the tissueLes modèles numériques personnalisables d'organes du corps humain offrent un formidable potentiel pour évaluer le risque lésionnel dans les domaines de la sécurité des transports, du médical ou du sport. Suivant les applications, différents niveaux de détails peuvent être nécessaires. En particulier, lorsque le comportement mécanique des tissus biologiques doit être finement reproduit, les modèles de comportement doivent intégrer des considérations sur la structure du tissu, et simuler les mécanismes suivant lesquels il réagit à un chargement mécanique. Le travail de thèse présenté ici s'est focalisé sur la capsule de foie, notamment sur ses propriétés microstructurales et mécaniques, afin d'identifier les hypothèses importantes à intégrer dans la construction d'un modèle constitutif de tissu fibreux basé sur la microstructure. La méthodologie expérimentale a été mise en place afin de caractériser le comportement mécanique de ce tissu, en lien avec l'organisation de sa microstructure. Des essais de traction uniaxiale et de gonflement sous microscope confocal biphotonique ont été développés, pour observer l'évolution de la microstructure sous chargement. Des déformations macroscopiques ont été mesurées, et une méthode de mesure de champs de déformations locaux a été développée pour quantifier l'état de déformation du réseau de fibres. La réorganisation du réseau de fibre de collagène a également été quantifiée. L'analyse des liens existant entre les grandeurs mesurées à l'échelle macroscopique et ces phénomènes microscopiques est proposée, pour préciser les hypothèses à adopter dans les modèles permettant de passer de l'échelle des fibres au comportement global du tiss

Localisation des endommagements dus à l'accouchement : simulation numérique du passage de la tête foetale

International audienceD'un point de vu mécanique, l'accouchement induit des sollicitations des tissus à l'origine d'endommagements. Afin de mieux localiser ces endommagements et les troubles induits par l'accouchement un modèle éléments finis, permettant de simuler le passage d'une tête fœtale à travers le système pelvien a été développé. Les éléments anatomiques subissant les déformations les plus importantes ont pu être identifiés. A partir de ce modèle, différentes situations d'accouchement pourront alors être modélisées, et leurs conséquences potentielles sur l'endommagement du système pelvien pourront être évaluées

Mechanical and microstructural characterization of Glisson's capsule behavior up to failure, for the prediction of human hepatic tissues injury risk

Les modèles numériques personnalisables d'organes du corps humain offrent un formidable potentiel pour évaluer le risque lésionnel dans les domaines de la sécurité des transports, du médical ou du sport. Suivant les applications, différents niveaux de détails peuvent être nécessaires. En particulier, lorsque le comportement mécanique des tissus biologiques doit être finement reproduit, les modèles de comportement doivent intégrer des considérations sur la structure du tissu, et simuler les mécanismes suivant lesquels il réagit à un chargement mécanique. Le travail de thèse présenté ici s'est focalisé sur la capsule de foie, notamment sur ses propriétés microstructurales et mécaniques, afin d'identifier les hypothèses importantes à intégrer dans la construction d'un modèle constitutif de tissu fibreux basé sur la microstructure. La méthodologie expérimentale a été mise en place afin de caractériser le comportement mécanique de ce tissu, en lien avec l'organisation de sa microstructure. Des essais de traction uniaxiale et de gonflement sous microscope confocal biphotonique ont été développés, pour observer l'évolution de la microstructure sous chargement. Des déformations macroscopiques ont été mesurées, et une méthode de mesure de champs de déformations locaux a été développée pour quantifier l'état de déformation du réseau de fibres. La réorganisation du réseau de fibre de collagène a également été quantifiée. L'analyse des liens existant entre les grandeurs mesurées à l'échelle macroscopique et ces phénomènes microscopiques est proposée, pour préciser les hypothèses à adopter dans les modèles permettant de passer de l'échelle des fibres au comportement global du tissuCustomized human body models offer a great potential to assess the injury risks in the fields of transport safety, surgery or sport. Various detail levels can then be needed, according to the targeted application. In particular, when the mechanical behavior of biological tissues needs to be accurately reproduced, numerical models have to include information about the structure of the tissue, and model the mechanisms of the response to mechanical loading. The work presented here focuses on the microstructural and mechanical characterization of the human liver capsule, in order to identify the important hypotheses that need to be included in a fibrous tissue constitutive model, based on microstructure. Thus, an experimental methodology has been developed to identify the mechanical behavior of this particular tissue, related with its microstructural organization. Uniaxial tensile tests, as well as bulge tests under a multiphoton confocal microscope have been performed, to observe the microstructure evolution during loading. Macroscopic strain has been assessed, and a method to measure local strain fields has been developed, to quantify the strain state of the fibrous network. The reorganization of the collagen fibers network has also been quantified. An analysis of the links between the measured macroscopic parameters and the microscopic phenomena is given. Therefore, the hypotheses that need to be included in constitutive models are highlighted, with particular consideration given to the affine transformation hypothesis which allows to link the fibers behavior to the global response of the tissu

Characterizing liver capsule microstructure via in situ bulge test coupled with multiphoton imaging

International audienceThe characterization of biological tissue at the microscopic scale is the starting point of many applications in tissue engineering and especially in the development of structurally based constitutive models. In the present study, focus is made on the liver capsule, the membrane encompassing hepatic parenchyma, which takes a huge part in liver mechanical properties. An in situ bulge test experiment under a multiphoton microscope has been developed to assess the microstructure changes that arise with biaxial loading. Multi-photon microscopy allows to observe the elastin and collagen fiber networks simultaneously. Thus a description of the microstructure organization of the capsule is given, characterizing the shapes, geometry and arrangement of fibers. The orientation of fibers is calculated and orientation distribution evolution with loading is given, in the case of an equibiaxial and two non equibiaxial loadings, thanks to a circular and elliptic set up of the bulge test. The local strain fields have also been computed, by the mean of a photobleach-ing grid, to get an idea of what the liver capsule might experience when subjected to internal pressure. Results show that strain fields present some heterogeneity due to anisotropy. Reorientation occurs in non equibiaxial loadings and involves fibers layers from the inner to the outer surface as expected. Although there is a fiber network rearrangement to accommodate with loading in the case of equibiaxial loading, there is no significant reorientation of the main fibers direction of the different layers

Imaging of the human Glisson's capsule by two-photon excitation microscopy and mechanical characterisation by uniaxial tensile tests

38ième congrès de la Société de Biomécanique francophone, MARSEILLE, FRANCE, 06-/09/2013 - 09/09/2013Mechanical properties of the liver have been well investigated through many studies at the macroscopic level. These studies allowed elaborating more or less sophisticated models providing material data. The rupture phenomenon has been studied as well, for example by Brunon et al. (2011) to collect data on how the liver, and more precisely the Glisson's capsule, responds to mechanical loading. With the emergence of multimodal microscopy, these phenomena have been considered to a whole different scale, as we can now investigate the behaviour of these materials at the microscopic level. This way, we can have a better understanding of damage and rupture mechanisms of these tissues, linking them to microstructure organisation and thus developing realistic models based on microstructure. Recent studies have therefore focused on imaging the microstructure organisation of biological materials during or after loading. For example, Goulam Houssen et al. (2011) have monitored the behaviour of the rat-tail collagen fibres during uniaxial loading using second harmonic generation (SHG) from two-photon excitation (TPE) microscopy. Keyes et al. (2013) used SHG and autofluorescence from TPE to image pressurised porcine coronary arteries and observed realignment of the fibres. Thus, the aim of this study was to observe how the different constitutive fibres of the Glisson's capsule are organised and how they react when subjected to uniaxial tensile loading, in order to understand how microstructural organisation impacts macro-mechanical properties. In the first step, we worked on the imaging of the Glisson's capsule by TPE to enforce our knowledge of its components and their state before loading. In the second step, we carried out preliminary tensile tests using an in situ micro-tensile stage to estimate mechanical parameters such as apparent modulus, ultimate stress and ultimate strain

Geometry of an inflated membrane in elliptic bulge tests: evaluation of an ellipsoidal shape approximation by stereoscopic digital image correlation measurements

Elliptic bulge tests are conducted on liver capsule, a fibrous connective membrane, associated with a field measurement method to assess the global geometry of the samples during the tests. The experimental set up is derived from a previous experimental campaign of bulge tests under microscope. Here, a stereoscopic Digital Image Correlation (DIC) system is used to measure global parameters on the test and investigate some assumptions made on the testing conditions which could not been assessed with microscopic measurements. In particular, the assumption of an ellipsoidal shape of the inflated membrane is tested by comparing the actual sample shape measured by stereoscopic DIC with an idealized ellipsoidal shape. Results indicate that a rather constant gap exists between the idealized and actual position. The approximation in the calculation of a macroscopic strain through analytical modeling of the test is estimated here. The study of the liver capsule case shows that important differences can be observed in strain calculation depending on the method and assumptions taken. Therefore, analytical modeling of mechanical tests through ellipsoidal approximation needs to be carefully evaluated in every application. Here the field measurement allows assessing the validity of these modeling assumptions. Moreover, it gives precious details about the boundary conditions of the bulge test and revealed the heterogeneous clamping, highlighted by strain concentrations

Photobleaching as a tool to measure the local strain field in fibrous membranes of connective tissues

Connective tissues are complex structures which contain collagen and elastin fibers. These fiber based structures have a great influence on material mechanical properties and need to be studied at the microscopic scale. Several microscopy techniques have been developed in order to image such microstructures; among them are two-photon excited fluorescence microscopy and second harmonic generation. These observations have been coupled with mechanical characterization to link microstructure kinematic to macroscopic material parameter evolution. In this study, we present a new approach to measure lo cal strain in soft biological tissues using a side effect of fluorescence microscopy: photobleaching. Controlling the loss of fluorescence induced by photobleaching, we create a pattern on our sample that we can monitor during mechanical loading. The image analysis allows computing 3D displacements of the patterns at various loading levels. Then, local strain distribution is derived using the finite element discretization on a four nodes element mesh created from our photobleached pattern. Photobleaching tests on human liver's capsule have revealed that this technique is non-destructive and has not any impact on mechanical properties. This method is likely to have other applications in biological material studies, considering that all collagen-elastin fibers based biological tissues possess autofluorescence properties, and thus can be photobleached

The mechanical response of the mouse cervix to tensile cyclic loading in term and preterm pregnancy: Data

These files contain mechanical data from a study evaluating the cyclic tensile loading properties of mouse cervices in normal gestation and 2 models of preterm birth. The exp_data folder contains a .xlsx files corresponding to each tested sample. Each file includes the experimental cyclic tensile data. The name of the file indicates the sample ID, which includes the the gestation day (NP = nonpregnant, d6 = gestation day 6, d12 = gestation day 12, d15 = gestation day 15, d18 = gestation day 18, d15LPS = infection PTB model on day 15, d15LPSsham = sham procedure of the infection model on day 15, d15RU486 = hormone withdrawal PTB model on day 15) and the sample number identifier. For example, “NP_1_raw_data” corresponds to the experimental data for nonpregnant sample #1 and “d6_3_raw_data” corresponds to the experimental data for gestation day 6 sample #3. In these files, the columns correspond to: the time [s], force [N], averaged cervical opening [mm], standard deviation of the cervical opening [mm], average width [mm], standard deviation of the width [mm], average length [mm], standard deviation of the length [mm], average height [mm], standard deviation of the height [mm], of the cervical sample. The cervical opening, average and standard deviation of the width, length, height, are determined via camera images. The time and force measurements are data from the universal testing machine

Assessment of the ultimate strain of the hepatic capsule for the prediction of liver surface laceration

IRCOBI conference, Lyon, France, 09-/09/2015 - 11/09/2015In the field of road safety, the prediction of abdominal injuries is a relevant issue, especially considering rear ? seat passengers such as children, elderly or obese individuals. Among abdominal organs, the liver is particularly vulnerable due to its weight and location. Moreover, the liver which is highly vascularized has a high level risk of severe hemorrhage when injured. Considering its three main components ? parenchyma, capsule and a dense vascular network - this complex organ has three main types of injury: hematoma, laceration and vascular failure. The liver also has a high level of variability in terms of geometry and mechanical properties which makes it difficult to model. The variability of mechanical properties of hepatic tissues is closely related to individual variability and to potential diseases of patients such as the case of steatotic liver due to obesity or diabetes, for which parenchyma is especially fragile. Global injury criteria were established on whole pressurized organs in terms of impact energy, impact velocity and peak pressure. Local mechanisms of vascular/parenchyma injuries during a freefall and severe frontal deceleration were also highlighted but not quantified in terms of local criteria. The present study focuses on liver surface laceration, involving capsule and parenchyma. The hypothesis of the authors is that this type of injury occurs because of an excessive pressure and thus an important tension on the liver surface during an impact. Thus, local failure criteria of the capsule and superficial parenchyma must be defined in view of the prediction of surface laceration occurrence. For a few years, the co ? authors, members of the French research network Impact Biomechanics Research Group, studied the mechanical behavior of hepatic tissues up to failure. In a first step, uniaxial and equibiaxial tensile tests were performed on isolated samples of capsule ? parenchyma and capsule in order to quantify the ultimate mechanical properties of the capsule. In a second step, the capsule pretension before sampling was assessed on isolated liver under various internal fluid pressures. During all these tests, the surface strain fields were measured on the hepatic capsule by digital image correlatio

Assessment of the ultimate strain of the hepatic capsule for the prediction of liver surface laceration

IRCOBI conference, Lyon, France, 09-/09/2015 - 11/09/2015In the field of road safety, the prediction of abdominal injuries is a relevant issue, especially considering rear ? seat passengers such as children, elderly or obese individuals. Among abdominal organs, the liver is particularly vulnerable due to its weight and location. Moreover, the liver which is highly vascularized has a high level risk of severe hemorrhage when injured. Considering its three main components ? parenchyma, capsule and a dense vascular network - this complex organ has three main types of injury: hematoma, laceration and vascular failure. The liver also has a high level of variability in terms of geometry and mechanical properties which makes it difficult to model. The variability of mechanical properties of hepatic tissues is closely related to individual variability and to potential diseases of patients such as the case of steatotic liver due to obesity or diabetes, for which parenchyma is especially fragile. Global injury criteria were established on whole pressurized organs in terms of impact energy, impact velocity and peak pressure. Local mechanisms of vascular/parenchyma injuries during a freefall and severe frontal deceleration were also highlighted but not quantified in terms of local criteria. The present study focuses on liver surface laceration, involving capsule and parenchyma. The hypothesis of the authors is that this type of injury occurs because of an excessive pressure and thus an important tension on the liver surface during an impact. Thus, local failure criteria of the capsule and superficial parenchyma must be defined in view of the prediction of surface laceration occurrence. For a few years, the co ? authors, members of the French research network Impact Biomechanics Research Group, studied the mechanical behavior of hepatic tissues up to failure. In a first step, uniaxial and equibiaxial tensile tests were performed on isolated samples of capsule ? parenchyma and capsule in order to quantify the ultimate mechanical properties of the capsule. In a second step, the capsule pretension before sampling was assessed on isolated liver under various internal fluid pressures. During all these tests, the surface strain fields were measured on the hepatic capsule by digital image correlatio