Caracterización mecánica y modelado numérico de la pared abdominal : desarrollo de una metodología de ayuda al diseño de mallas sintéticas para la reparación herniaria.

La cirugía abdominal mediante la implantación de mallas sintéticas es la más utilizada para la reparación de hernias, pero estas mallas pueden causar varios problemas a los pacientes. Hoy en día, existe una gran variedad de mallas y no está científicamente demostrado cuál es la prótesis ideal ni cuáles son las pautas de orientación de las mismas en el cuerpo humano cuando se trata de mallas anisótropas. Las prótesis actuales han sufrido modicaciones en su estructura y su porosidad en los últimos tiempos con el objetivo de mejorar su adaptación al tejido. A pesar de estas mejoras, la "prótesis ideal" no ha sido obtenida, siendo común la reaparición de las hernias. Para entender el fenómeno es esencial que se caracterize mecánicamente la pared abdominal. Para entender dicho comportamiento es necesario distinguir entre las fibras de colágeno y las musculares, porque en el tejido del músculo, las fibras de colágeno son las responsables de la resistencia mecánica y rigidez y las fibras musculares de la contracción. La dirección de las fibras de colágeno determinan la dirección de anisotropía del material, propiedad a tener en cuenta posteriormente en la formulación del modelo constitutivo. Debido a la distinta orientación de las fibras en cada capa (fibras musculares y de colágeno), en este estudio se analiza la influencia del estudio de las capas separadas en comparación con el músculo en conjunto considerándolo como un material compuesto. Una vez que se ha entendido el comportamiento mecánico del músculo, se caracterizan tres mallas quirúrgicas utilizadas en la reparación herniaria. A su vez, se compara su comportamiento con el de la pared abdominal para estudiar qué malla es la que mejor reproduce el comportamiento de la pared abdominal. En el contexto del modelado matemático, se ha denido un modelo constitutivo 3D hiperelástico anisótropo cuasi-incompresible para el músculo abdominal y otro 2D para las mallas. Utilizando los datos experimentales y realizando un ajuste numérico se han obtenido un conjunto de parámetros, para la función densidad de energía planteada en cada caso, que son capaces de reproducir el comportamiento real del músculo abdominal y de cada una de las mallas mediante un modelo de elementos finitos (FE). En último lugar, con el objetivo de reproducir el comportamiento del abdomen sin dañar y el abdomen que ha sufrido una cirugía abdominal, se plantea un modelo simplificado de elementos finitos que simula el abdomen del animal de experimentación utilizado sometido a una presión abdominal interna. Con este modelo se trata de ver cómo se comporta el conjunto del abdomen bajo la presencia de las diferentes mallas estudiadas

Biomechanical behaviour of human bile duct wall and impact of cadaveric preservation processes.

International audienceBiliary diseases are the third most common cause of surgical digestive disease. There is a close relationship between the mechanical performance of the bile duct and its physiological function. Data of biomechanical properties of human main bile duct are scarce in literature. Furthermore, mechanical properties of soft tissues are affected by these preservation procedures. The aim of the present work was, on the one hand, to observe the microstructure of the human bile duct by means of histological analysis, on the other hand, to characterize the mechanical behavior and describe the impact of different preservation processes. A mechanical study in a controlled environment consisting of cyclic tests was made. The results of the mechanical tests are discussed and explained using the micro-structural observations. The results show an influence of the loading direction, which is representative of an anisotropic behavior. A strong hysteresis due to the viscoelastic properties of soft tissues was also observed. Embalming and freezing preservation methods had an impact on the biomechanical properties of human main bile duct, with fiber network deterioration. That may further provide a useful quantitative baseline for anatomical and surgical training using embalming and freezing

Advancing the Extraction of Mechanical Properties from Biaxial Data

Mechanical characterization is vital to understand soft tissue behaviour in health and pathology. In aortic aneurysms, for instance, it is used to develop techniques for rupture risk assessment. In skin, for instance, it is used to assess the effects of freezing and anatomic location, the information useful for donor tissue banks. Planar biaxial testing is one of the most common tools for the mechanical characterization of soft tissues. In this experiment, loadings such as displacements or forces are applied to the edges of the square specimens yielding deformations at the center of the specimens that are measured digitally. Biaxial testing is a great tool as it captures anisotropy and nonlinearity of soft tissues’ behaviour and is capable of exploring a wide range of deformation states as it can apply different combinations of loadings. However, because the deformations at the center of the specimens are not controlled, no two mechanical tests are equivalent, complicating the consistency in data extraction and comparison. In this study, we propose a new approach for biaxial data analysis. First, a surface is fitted to the biaxial data. Second, the mechanical response is interpolated at the true equi-biaxial stretch deformation state (the state at which the deformations at the center of the sample are equal). Third, the effective mechanical properties such as high/low elastic moduli, and transition stretches/stress are extracted from the interpolated response. Other studies, in contrast, extract properties at the equi-biaxial displacement deformation state (the state at which equal strains are applied at the sample edges), which is due to the anisotropy of soft tissues and experimental setup, varies from specimen to specimen. We argue that our proposed approach of data extraction is more robust from the mechanical point of view. To demonstrate that our proposed approach can result in drastically different data sets, we apply it to previously tested aortic tissues from human donors and pigs. We compare effective mechanical properties extracted from the interpolated equi-biaxial stretch deformation state and conventionally used equi-biaxial displacement deformation state. Statistical analysis shows a significant difference between two groups of mechanical measures whether the measures are compared individually within each group or the general comparison of groups is conducted. Particularly, measures related to the transition zones (stress/stretch) linked to collagen fibres’ engagement behaviour were affected the most. Overall, the results indicate that the way the data is extracted can impact the outcome of biaxial studies. This further highlights the advantage of using the proposed approach of biaxial data extraction at equivalent deformation states versus the conventional approach. The proposed approach of the data extraction was also applied to human skin samples that came from the same donor’s back. Prior to biaxial testing, the samples were frozen/stored using three different freezing protocols (wet freezing in Phosphate Buffered Salin alone and with the cryoprotectant Glycerol as well as dry freezing using Liquid Nitrogen). Then, after testing, the effective mechanical properties were extracted and the effects of freezing and the anatomic locations were evaluated. We found very little quantitive evidence that the freezing storage approach mattered, although some qualitative observations were made to highlight the distinct behaviour of the samples frozen using Liquid Nitrogen. In the case of heterogeneity analysis, samples closer to the spine were different from samples further away from the spine, with the transition zone properties affected the most, especially for the samples subjected to Liquid Nitrogen freezing protocol. Future studies should assess each of the effect of heterogeneity and the effects of freezing separately, however, the overall approach of data extraction seems promising for intra-patient analysis

Multiscale mechano-morphology of soft tissues : a computational study with applications to cancer diagnosis and treatment

Cooperation of engineering and biomedical sciences has produced significant advances in healthcare technology. In particular, computational modelling has led to a faster development and improvement of diagnostic and treatment techniques since it allows exploring multiple scenarios without additional complexity and cost associated to the traditional trial-and-error methodologies. The goal of this thesis is to propose computational methodologies to analyse how the changes in the microstructure of soft tissues, caused by different pathological conditions, influence the mechanical properties at higher length scales and, more importantly, to detect such changes for the purpose of quantitative diagnosis and treatment of such pathologies in the scenario of drug delivery. To achieve this objective different techniques based on quasi-static and dynamic probing have been established to perform quantitative tissue diagnosis at the microscopic (tissue) and macroscopic (organ) scales. The effects of pathologies not only affect the mechanical properties of tissue (e.g. elasticity and viscoelasticity), but also the transport properties (e.g. diffusivity) in the case of drug delivery. Such transport properties are further considered for a novel multi-scale, patient-specific framework to predict the efficacy of chemotherapy in soft tissues. It is hoped that this work will pave the road towards non-invasive palpation techniques for early diagnosis and optimised drug delivery strategies to improve the life quality of patientsJames-Watt Scholarship, Heriot-Watt Annual Fund and the Institute of Mechanical, Process and Energy Engineering (IMPEE) Grant

IMPACT OF VAGINAL SYNTHETIC PROLAPSE MESHES ON THE MECHANICS OF THE HOST TISSUE RESPONSE

The vagina helps support the bladder, urethra, uterus, and rectum. A lack of support leads to pelvic organ prolapse, and vaginal delivery is a prevalent risk factor; however, there is little research on vaginal biomechanical properties. Despite numerous complications, clinical practice involves surgical repair with synthetic meshes. Complications can be partially attributed to our lack of knowledge regarding the mesh-tissue complex (MTC) after implantation. However, it is difficult to perform rigorous studies without utilizing animal models. Therefore, we evaluated how parity affected the mechanical properties of vaginal tissue in three animal models: rodent, sheep, and non-human primate (NHP) to compare their mechanically properties to parous women who typically undergo prolapse surgery. Parity negatively impacted the mechanical properties of the vagina in NHP, which were biomechanically similar to parous women, making it a suitable model for studying the effects of mesh implantation. Second, we examined the textile and structural properties of commonly used meshes (Gynemesh, UltraPro, SmartMesh, Novasilk, and Polyform) utilizing uniaxial and ball-burst tests. These meshes had significantly different porosity and structural properties. To investigate the host response, three meshes were implanted into the abdominal wall of the rodent and NHP, and on the vagina in the NHP. The MTC was removed, and the tissue contribution was calculated. We did not observe notable changes in the tissue properties following mesh implantation in the rodent; however, implantation of the stiffest mesh (Gynemesh) in the NHP resulted in an exhibition of a stress-shielding response manifested by inferior biomechanical properties of the abdominal and vaginal tissues. Less stiff meshes (UltraPro and SmartMesh) resulted in preservation of tissue properties. To gain insight into how mesh properties affect the tissue contribution, we began developing a finite element model. Utilizing the co-rotational theory with a fiber-recruitment stress-strain relationship, we could describe the behavior of SmartMesh and UltraPro. While an in-depth characterization of these meshes revealed multiple fiber populations, further development of modeling may be instrumental in closing the current knowledge gap. Ultimately, understanding the mesh-tissue interaction will improve clinical outcomes by identifying mesh properties that are essential for providing structural support while maintaining tissue integrity

Mechanical modelling of the abdominal wall and biomaterials for hernia surgery

Abdominal surgery for hernia repair is based on the implantation of a synthetic mesh in the defect area which aims at reinforcing the damaged wall. This clinical intervention is common in today's society and, in unfavorable cases such as obese patients or patients with large defects, could lead to a number of problems that reduce the quality of life of patients. The most common problems are the appearance of fibrosis, the hernia recurrence and occurrence of abdominal discomfort due to poor compliance between the host tissue and the prosthesis. Currently, surgeons have no definitive and universally accepted guidelines for the selection of the appropriate prosthesis for each patient and type of defect. Therefore, the choice of one or another mesh, and their placement in case of anisotropic meshes, is a decision to be taken by the surgeons according to their experience. This thesis aims to study the abdominal hernia surgery from the continuum mechanics point of view. However, for the supply and validation of the generated models, it is necessary to perform an experimental study in an animal model. Since this is a multidisciplinary problem, the study approached was developed in collaboration with the Translational Research Group in Biomaterials and Tissue Engineering at the University of Alcalá de Henares (Madrid). The final goal of hernia surgery is that the prosthesis ensures adequate tissular integration, being capable, among other things, to reproduce the mechanical behaviour of the healthy abdominal wall and to absorb the stresses due to the physiological loads to which the abdomen is subjected. Therefore, in addition to addressing the study in animal models to analyze the integration on the wall, the mechanical modelling of the abdominal wall and the biomaterials used in hernia repair is essential. For this, the construction of an ``in silico'' model of the human abdomen has been developed. Due to the diversity of commercial products on the market, this thesis focusses on the study of three representative prostheses, specifically Surgipro, Optilene and Infinit. These meshes are characterized by different geometric parameters and are made of different materials. In this work, the mechanical properties of the prostheses have been determined experimentally and different constitutive models, that reproduce the patterns of the mechanical behaviour observed in both, the abdominal muscle and implanted biomaterials, have been proposed. Specifically, the numerical modelling of the response of the abdominal muscle, including both active and passive responses, and prostheses have been approached within the framework of the nonlinear hyperelasticity in large deformations. The latter approach of this thesis aims to model, using the finite element method, the mechanical response of the wall with the implanted mesh. A complete model of the human abdomen has been defined from nuclear magnetic resonance imaging. This complete model allows differentiating the main anatomical units of the abdomen and it is used to simulate the passive and active responses. Furthermore, this model allows the study of the response of the healthy wall and the analysis of the final mechanical response of the herniated human abdomen to the placement of different prostheses. In summary, this thesis establishes a methodology to the automation of computational models for personalized surgical procedures in order to select the most appropriate mesh for each patient as well as the appropriate placement on the defect in the case of anisotropic prostheses

Ex vivo experimental investigations and modelling of the layer-dependent, anisotropic, visco-hyperelastic behaviour of the human oesophagus

As a mechanical organ, the material properties of the oesophagus are integral to its function. The quantification of these properties is necessary to investigate the organ’s pathophysiology and is required for a range of applications including medical device design, surgical simula-tions and tissue engineering. However, according to a systematic review of mechanical exper-imentation conducted on the gastrointestinal organs, the discrete layer-dependent properties of the oesophagus have not been investigated using human tissue, especially regarding its vis-coelastic and stress-softening behaviour. Therefore, extensive experimentation was conducted to determine the time, layer and direction-dependent material response of the oesophagus us-ing cadaveric human tissue. The residual strains of the organ were also considered via opening angle experiments. Overall, the results showed distinct properties in each layer, highlighting the importance of treating the oesophagus as a multi-layered composite material. Furthermore, a strong anisotropy was exhibited across both layers, where the longitudinal directions were much stiffer than the circumferential directions. Due to the COVID-19 pandemic, fresh human cadavers were not available from the anatomy laboratory for a considerable amount of time. Therefore, mechanical testing was first completed on embalmed human tissue and then, once available, on fresh human tissue. This unforeseen circumstance, through comparison of the two preservation states, allowed for an interesting discussion on the role of the tissue’s con-stituents on its complex material behaviour. In addition, histological analysis was carried out to determine the density of the oesophagus’ most mechanically relevant fibres: collagen and elastin. This knowledge was then used to inform constitutive modelling of the soft tissue’s behaviour, the outcome of which was able to capture the anisotropy, visco-hyperelasticity and stress-softening observed in the experimental data

Biomechanical relevance of the microstructure in artery walls with a focus on passive and active components

The microstructure of arteries, consisting, in particular, of collagen, elastin and vascular smooth muscle cells, plays a very significant role in their biomechanical response during a cardiac cycle. In this paper we highlight the microstructure and the contributions of each of its components to the overall mechanical behavior. We also describe the changes of the microstructure which occur as a result of abdominal aortic aneurysms and disease such as atherosclerosis. We also focus on how the passive and active constituents are incorporated into a mathematical model without going into detail of the mathematical formulation. We conclude by mentioning open problems towards a better characterization of the biomechanical aspects of arteries that will be beneficial for a better understanding of cardiovascular pathophysiology

Multiphysical modelling of mechanical behaviour of soft tissue : application to prostate

The aim of this thesis is to propose computational methodologies to analyse how the morphological and microstructural changes in the soft tissues, caused by various pathological conditions, influence the mechanical properties of tissue. More importantly, how such understanding could provide more insights into the mechanical properties of tissue for the purpose of quantitative diagnosis. To achieve this objective, statistical analysis of tissue microstructure based on image processing of tissue histology has been carried out. The influence of such microstructural changes due to different pathological conditions has also been compared to the mechanical properties of the tissue by means of the homogenization approach. To understand better the influence of fluid movement in viscoelastic behaviour of tissue, an optimization based method using numerical homogenization that is integrated with fluid-structure interaction (FSI) modelling is presented. The microstructures of soft tissue are treated as bi-phasic materials, solid material representing the cells and extracellular materials and fluid phase for the interstitial fluid. Such proposed method would be beneficial for quantitative assessment of mechanical properties of soft tissue, as well as understanding the role of multiscale microstructural features of soft tissues in its functionality. It is envisaged that this work will pave the road towards more precise characterization of mechanical properties of soft tissue which can be implemented to non-invasive diagnostic techniques, in order to improve the effectiveness of a range of diagnostic methods such as palpation for primary prostate diagnosis and, more importantly, the life quality of patients

A hybrid approach to determining cornea mechanical properties using a combination of inverse finite element analysis and experimental techniques

It is of great clinical importance to predict the behaviour of the cornea in various diseases and post-surgical recovery. Therefore, a numerical model that is able to simulate the corneal behaviour, considering corneal material properties obtained from individuals is highly desirable. In this work a combined numerical-experimental technique has been developed that can characterize the mechanical properties of a cornea properties from two aspects: time-dependency and spatial variation. Initially, an analysis of the material properties of porcine corneas was performed to investigate the time-dependent behaviour of the cornea. A simple stress relaxation test was used to determine the viscoelastic properties of a cornea and a rheological model was built based on the Generalized Maxwell (GM) approach. A validation experiment using nano-indentation showed that an isotropic GM model was insufficient for describing the corneal time-dependent behaviour when exposed to a complex stress state. A technique was proposed that takes into account the microstructural composition of the cornea and is based on a combination of nano-indentation experiment, isotropic and transversely isotropic numerical models, and an inverse finite element method. The good agreement using this method suggests that this is a promising technique for measuring the time-dependent properties of the cornea. The spatial variation of the properties was then investigated. This time, the long term structural response of the cornea was targeted. A full field displacement response of a loaded cornea was evaluated from Optical Coherence Tomography (OCT) volume reconstructions of the cornea using Digital Volume Correlation (DVC). The inverse finite element method was employed with two models sequentially; first, a radially partitioned model and then a circumferentially partitioned model, in order to recover the elastic parameters in radial and circumferential directions. The good agreement using this method suggests that this is a promising and reliable technique for identifying the distribution of the corneal properties. In this research, we have shown that it is possible to determine the local time-dependent properties of the cornea and the in-depth (2D) distribution of the properties using the hybrid technique. This technique has the potential to be implemented in vivo. However, further work should focus on the feasibility of this technique in practice