An inverse fitting strategy to determine the constrained mixture model parameters: application in patient-specific aorta.

The Constrained Mixture Model (CMM) is a novel approach to describe arterial wall mechanics, whose formulation is based on a referential physiological state. The CMM considers the arterial wall as a mixture of load-bearing constituents, each of them with characteristic mass fraction, material properties, and deposition stretch levels from its stress-free state to the in-vivo configuration. Although some reports of this model successfully assess its capabilities, they barely explore experimental approaches to model patient-specific scenarios. In this sense, we propose an iterative fitting procedure of numerical-experimental nature to determine material parameters and deposition stretch values. To this end, the model has been implemented in a finite element framework, and it is calibrated using reported experimental data of descending thoracic aorta. The main results obtained from the proposed procedure consist of a set of material parameters for each constituent. Moreover, a relationship between deposition stretches and residual strain measurements (opening angle and axial stretch) has been numerically proved, establishing a strong consistency between the model and experimental data.

Analysis of the geometrical influence of ring-opening samples on arterial circumferential residual stress reconstruction.

This work consists of analyzing the impact of geometrical features (thickness and curvature) on the estimation of circumferential residual stresses in arteries. For this purpose, a specific sample of lamb abdominal artery is chosen for analysis and, through computational tools based on Python libraries, the stress-free geometry is captured after the ring opening test. Numerical simulations are then used to reconstruct the sample in order to estimate the circumferential residual stresses. Then, four stress-free geometry models are analyzed: an ideal geometry, i.e., constant curvature and thickness; a constant curvature and variable thickness geometry; a variable curvature and constant thickness geometry; and a variable curvature and thickness geometry. The numerical results show that models perform well from a geometric point of view, where the most different feature was the closed outer perimeter that differs about 14% from the closed real sample. As far as residual stress is concerned, differences up to 198% were found in more realistic models taking a constant curvature and thickness model as reference. Thus, the analysis of a realistic geometry with highly variable curvature and thickness can introduce, compared to an idealized geometry, significant differences in the estimation of residual stresses. This could indicate that the characterization of arterial residual stresses is not sufficient when considering only the opening angle and, therefore, it is also necessary to incorporate more geometrical variables.

Hyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat.

Chronic hypoxia during gestation and postnatal period induces pulmonary hypertension, aorta stiffening and vascular remodeling. In this study, we hypothesized that a postnatal treatment with Cinaciguat, a guanylate cyclase activator, may improve the vascular function by enhancing NO-sGC pathways that induce vasodilation. To assess this, we collected aortas from six lambs gestated, born and raised at 3600 masl. Half of these lambs received a Cinaciguat postnatal treatment, while the other half was used as control (vehicle). Uniaxial tension was applied on samples of each group of aortas (control and Cinaciguat-treated) through cyclic loading. The obtained stress-stretch curves were used to identify constitutive parameters of a hyperelastic damage model. These material constants allowed us to assess the softening/dissipation behavior and to characterize the treatment effects. Results showed that Cinaciguat has an effect on the damage behavior at large strains, altering the damage onset under uniaxial tension. We conclude that Cinaciguat, as a vasodilator, can prevent the very early effects of vascular remodeling caused by perinatal hypoxia, and improve the aortic-tissue damage properties of hypoxic lambs.

Characterization of the active response of a guinea pig carotid artery.

This work presents a characterization of the active response of the carotid artery of guinea pig fetuses through a methodology that encompasses experiments, modeling and numerical simulation. To this end, the isometric contraction test is carried out in ring samples subjected to different levels of KCl concentrations and pre-stretching. Then, a coupled mechanochemical model, aimed at describing the smooth cell behavior and its influence on the passive and active mechanical response of the vascular tissue, is calibrated from the experimental measurements. Due to the complex stress and strain fields developed in the artery, a finite element numerical simulation of the test is performed to fit the model parameters, where those related to the phosphorylation and dephosphorylation activity along with the load-bearing capacity of the myosin cross-bridges are found to be the most predominant when sensitizing the active response. The main strengths of the model are associated with the prediction of the stationary state of the active mechanical response of the tissue through a realistic description of the mechanochemical process carried out at its cellular level.

Evaluation of remodeling and geometry on the biomechanical properties of nacreous bivalve shells.

Mollusks have developed a broad diversity of shelled structures to protect against challenges imposed by biological interactions(e.g., predation) and constraints (e.g., [Formula: see text]-induced ocean acidification and wave-forces). Although the study of shell biomechanical properties with nacreous microstructure has provided understanding about the role of shell integrity and functionality on mollusk performance and survival, there are no studies, to our knowledge, that delve into the variability of these properties during the mollusk ontogeny, between both shells of bivalves or across the shell length. In this study, using as a model the intertidal mussel Perumytilus purpuratus to obtain, for the first time, the mechanical properties of its shells with nacreous microstructure; we perform uniaxial compression tests oriented in three orthogonal axes corresponding to the orthotropic directions of the shell material behavior (thickness, longitudinal, and transversal). Thus, we evaluated whether the shell material's stress and strain strength and elastic modulus showed differences in mechanical behavior in mussels of different sizes, between valves, and across the shell length. Our results showed that the biomechanical properties of the material building the P. purpuratus shells are symmetrical in both valves and homogeneous across the shell length. However, uniaxial compression tests performed across the shell thickness showed that biomechanical performance depends on the shell size (aging); and that mechanical properties such as the elastic modulus, maximum stress, and strain become degraded during ontogeny. SEM observations evidenced that compression induced a tortuous fracture with a delamination effect on the aragonite mineralogical structure of the shell. Findings suggest that P. purpuratus may become vulnerable to durophagous predators and wave forces in older stages, with implications in mussel beds ecology and biodiversity of intertidal habitats.

Analysis of the passive biomechanical behavior of a sheep-specific aortic artery in pulsatile flow conditions.

In this work, a novel numerical-experimental procedure is proposed, through the use of the Cardiac Simulation Test (CST), device that allows the exposure of the arterial tissue to in-vitro conditions, mimicking cardiac cycles generated by the heart. The main goal is to describe mechanical response of the arterial wall under physiological conditions, when it is subjected to a variable pressure wave over time, which causes a stress state affecting the biomechanical behavior of the artery wall. In order to get information related to stress and strain states, numerical simulation via finite element method, is performed under a condition of systolic and diastolic pressure. The description of this methodological procedure is performed with a sample corresponding to a sheep aorta without cardiovascular pathologies. There are two major findings: the evaluation of the mechanical properties of the sheep aorta through the above-mentioned tests and, the numerical simulation of the mechanical response under the conditions present in the CST. The results state that differences between numerical and experimental circumferential stretch in diastole and systole to distinct zones studied do not exceed 1%. However, greater discrepancies can be seen in the distensibility and incremental modulus, two main indicators, which are in the order of 30%. In addition, numerical results determine an increase of the principal maximum stress and strain between the case of systolic and diastolic pressure, corresponding to 31.1% and 14.9% for the stress and strain measurement respectively; where maximum values of these variables are located in the zone of the ascending aorta and the aortic arch.

Biomechanical Characterization of Scallop Shells Exposed to Ocean Acidification and Warming.

Increased carbon dioxide levels (CO2) in the atmosphere triggered a cascade of physical and chemical changes in the ocean surface. Marine organisms producing carbonate shells are regarded as vulnerable to these physical (warming), and chemical (acidification) changes occurring in the oceans. In the last decade, the aquaculture production of the bivalve scallop Argopecten purpuratus (AP) showed declined trends along the Chilean coast. These negative trends have been ascribed to ecophysiological and biomineralization constraints in shell carbonate production. This work experimentally characterizes the biomechanical response of AP scallop shells subjected to climate change scenarios (acidification and warming) via quasi-static tensile and bending tests. The experimental results indicate the adaptation of mechanical properties to hostile growth scenarios in terms of temperature and water acidification. In addition, the mechanical response of the AP subjected to control climate conditions was analyzed with finite element simulations including an anisotropic elastic constitutive model for a two-fold purpose: Firstly, to calibrate the material model parameters using the tensile test curves in two mutually perpendicular directions (representative of the mechanical behavior of the material). Secondly, to validate this characterization procedure in predicting the material's behavior in two mechanical tests.

Study of the Effect of Treatment With Atrial Natriuretic Peptide (ANP) and Cinaciguat in Chronic Hypoxic Neonatal Lambs on Residual Strain and Microstructure of the Arteries.

In this study, we assessed the effects of Atrial Natriuretic Peptide (ANP) and Cinaciguat, as experimental medicines to treat neonatal lambs exposed to chronic hypoxic conditions. To compare the different treatments, the mechanical responses of aorta, carotid, and femoral arterial walls were analyzed by means of axial pre-stretch and ring-opening tests, through a study with n = 6 animals for each group analyzed. The axial pre-stretch test measures the level of shortening in different zones of the arteries when extracted from lambs, while the ring-opening test is used to quantify the degree of residual circumferential deformation in a given zone of an artery. In addition, histological studies were carried out to measure elastin, collagen, and smooth muscle cell (SMC) nuclei densities, both in control and treated groups. The results show that mechanical response is related with histological results, specifically in the proximal abdominal aorta (PAA) and distal carotid zones (DCA), where the cell nuclei content is related to a decrease of residual deformations. The opening angle and the elastic fibers of the aorta artery were statistically correlated (p < 0.05). Specifically, in PAA zone, there are significant differences of opening angle and cell nuclei density values between control and treated groups (p-values to opening angle: Control-ANP = 2 ⋅ 10-2, Control-Cinaciguat = 1 ⋅ 10-2; p-values to cell nuclei density: Control-ANP = 5 ⋅ 10-4, Control-Cinaciguat = 2 ⋅ 10-2). Respect to distal carotid zone (DCA), significant differences between Control and Cinaciguat groups were observed to opening angle (p-value = 4 ⋅ 10-2), and cell nuclei density (p-value = 1 ⋅ 10-2). Our findings add evidence that medical treatments may have effects on the mechanical responses of arterial walls and should be taken into account when evaluating the complete medical outcome.

Efectos morfológicos y mecánicos en ratas Sprague Dawley sometidas a ciclos de hipoxia / Morphological and mechanical effects in Sprague Dawley rats subjected to hypoxia cycles

Periodos extensos de hipoxia provocan cambios adaptativos que permiten responder a las demandas impuestas por el ambiente. Sin embargo, existen casos donde esta exposición es intermitente, como es el caso de los trabajadores en zonas andinas. El objetivo de esta comunicación fue comprobar los efectos morfológicos y mecánicos en diafragma y pulmones de ratas sometidas a la hipoxia intermitente. Se utilizaron 4 ratas Sprague Dawley de 6 meses de edad. Dos ratas fueron sometidas a 10 ciclos de hipoxia hipobárica intermitente (HHI) de 96 h (~428 torr; PO2 90 mm Hg), seguidos de 96 h de normoxia normobárica, durante 80 días. Se realizaron pruebas tracción uniaxial y de tinción con HematoxilinaEosina y Picrosirius red de Junqueira. Al comparar las curvas de los diafragmas, los sometidos a hipoxia reducen levemente su esfuerzo respecto a la condición de normoxia, en el tejido pulmonar la hipoxia afecta negativamente su resistencia, estas muestran una pendiente menor respecto a las normóxicas. En el análisis histológico, el parénquima pulmonar presentó menor cantidad de vasos sanguíneos y celularidad, como una mayor fracción de área de los espacios alveolares y cantidad de colágeno total en el grupo HHI. En el diafragma, el grupo HHI presentó menor cantidad de miocitos distribuidos irregularmente y de colágeno total. En conclusión, los principales hallazgos indican que el diafragma y el tejido pulmonar sometido a HHI sufren cambios estructurales, que se traducen en una disminución en su capacidad de resistencia tensil.

Extensive periods of hypoxic cause adaptive changes that make it possible to respond to the demands imposed by the environment. However, there are cases where this exposure is intermittent, as is the case of workers in andean areas. The objective of this communication was to verify the morphological and mechanical effects on diaphragm and lungs of rats subjected to intermittent hypoxic. Four 6-monthold Sprague Dawley rats were used. Two rats were subjected to 10 cycles of intermittent hypobaric hypoxic (IHH) of 96 h (~428 torr, PO2 90 mm Hg), followed by 96 h of normobaric normoxia, for 80 days. Uniaxial traction and staining tests were performed with Hematoxylin-Eosin and Picrosirius red de Junqueira. When comparing the curves of the diaphragms, those subjected to hypoxic slightly reduce their effort with respect to the condition of normoxia, in the lung tissue the hypoxic negatively affects its resistance, these show a lower slope with respect to the normoxics. In the histological analysis, the pulmonary parenchyma had a lower number of blood vessels and cellularity, such as a greater area fraction of alveolar spaces and amount of total collagen in IHH group. In the diaphragm, IHH group had a lower number of irregularly distributed myocytes and a lower amount of total collagen. In conclusion, the main findings indicate that the diaphragm and lung tissue subjected to IHH undergo structural changes, which result in a decrease in tensile strength.

Author Correction: Rapid fabrication of reinforced and cell-laden vascular grafts structurally inspired by human coronary arteries.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Rapid fabrication of reinforced and cell-laden vascular grafts structurally inspired by human coronary arteries.

Design strategies for small diameter vascular grafts are converging toward native-inspired tissue engineered grafts. A new automated technology is presented that combines a dip-spinning methodology for depositioning concentric cell-laden hydrogel layers, with an adapted solution blow spinning (SBS) device for intercalated placement of aligned reinforcement nanofibres. This additive manufacture approach allows the assembly of bio-inspired structural configurations of concentric cell patterns with fibres at specific angles and wavy arrangements. The middle and outer layers were tuned to structurally mimic the media and adventitia layers of native arteries, enabling the fabrication of small bore grafts that exhibit the J-shape mechanical response and compliance of human coronary arteries. This scalable automated system can fabricate cellularized multilayer grafts within 30 min. Grafts were evaluated by hemocompatibility studies and a preliminary in vivo carotid rabbit model. The dip-spinning-SBS technology generates constructs with native mechanical properties and cell-derived biological activities, critical for clinical bypass applications.

Mechanical characterization of arteries affected by fetal growth restriction in guinea pigs (Cavia porcellus).

Fetal growth restriction (FGR) is a perinatal condition associated with a low birth weight that results mainly from maternal and placental constrains. Newborns affected by this condition are more likely to develop in the long term cardiovascular diseases whose origins would be in an altered vascular structure and function defined during fetal development. Thus, this study presents the modeling and numerical simulation of systemic vessels from guinea pig fetuses affected by FGR. We aimed to characterize the biomechanical properties of the arterial wall of FGR-derived the aorta, carotid, and femoral arteries by performing ring tensile and ring opening tests and, based on these data, to simulate the biomechanical behavior of FGR vessels under physiological conditions. The material parameters were first obtained from the experimental data of the ring tensile test. Then, the residual stresses were determined from the ring opening test and taken as initial stresses in the simulation of the ring tensile test. These two coupled steps are iteratively considered in a nonlinear least-squares algorithm to obtain the final material parameters. Then, the stress distribution changes along the arterial wall under physiological pressure were quantified using the adjusted material parameters. Overall, the obtained results provide a realistic approximation of the residual stresses and the changes in the mechanical behavior under physiological conditions.

Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

Mechanical analysis of the ring opening test applied to human ascending aortas.

This work presents experiments, modelling and numerical simulation aimed at describing the mechanical response of human ascending aortas in the ring opening test. The objective is to quantify, from the opening angles measured in the test, the residual stress distribution along the artery wall and, afterwards, how this stress pattern changes when the artery is subjected to standard physiological pressures. The cases studied correspond to four groups including both healthy and pathological arteries. The tissues are characterized via tensile test measurements that enable to derive the material parameters of two constitutive models adopted in the present analysis. Overall, the numerical results obtained for all groups were found to be a useful data that allow to estimate the residual stress and their influence on the vessels under normal and hypertension physiological conditions.

Modelling and simulation of the mechanical response of a Dacron graft in the pressurization test and an end-to-end anastomosis.

This work presents the modeling and simulation of the mechanical response of a Dacron graft in the pressurization test and its clinical application in the analysis of an end-to-end anastomosis. Both problems are studied via an anisotropic constitutive model that was calibrated by means of previously reported uniaxial tensile tests. First, the simulation of the pressurization test allows the validation of the experimental material characterization that included tests carried out for different levels of axial stretching. Then, the analysis of an end-to-end anastomosis under an idealized geometry is proposed. This case consists in evaluating the mechanical performance of the graft together with the stresses and deformations in the neighborhood of the Dacron with the artery. This research contributes important data to understand the functioning of the graft and the possibility of extending the analysis to complex numerical cases like its insertion in the aortic arch.

Mechanical characterisation of Dacron graft: Experiments and numerical simulation.

Experimental and numerical analyses focused on the mechanical characterisation of a woven Dacron vascular graft are presented. To that end, uniaxial tensile tests under different orientations have been performed to study the anisotropic behaviour of the material. These tests have been used to adjust the parameters of a hyperelastic anisotropic constitutive model which is applied to predict through numerical simulation the mechanical response of this material in the ring tensile test. The obtained results show that the model used is capable of representing adequately the nonlinear elastic region and, in particular, it captures the progressive increase of the rigidity and the anisotropy due to the stretching of the Dacron. The importance of this research lies in the possibility of predicting the graft׳s mechanical response under generalized loading such as those that occur under physiological conditions after surgical procedures.

Modelling and numerical simulation of the human aortic arch under in vivo conditions.

This work presents the modelling and simulation of the mechanical behaviour of the human aortic arch under in vivo conditions with pressure levels within the normal and hypertension physiological range. The cases studied correspond to young and aged arteries without cardiovascular pathologies. First, the tissue of these two groups is characterised via in vitro tensile test measurements that make it possible to derive the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters are used in the simulation of young and aged aortic arches subjected to in vivo normal and hypertension conditions. Overall, the numerical results were found not only to provide a realistic description of the mechanical behaviour of the vessel but also to be useful data that allow the adequate definition of stress/stretch-based criteria to predict its failure.

Bending and pressurisation test of the human aortic arch: experiments, modelling and simulation of a patient-specific case.

This work presents experiments, modelling and simulation aimed at describing the mechanical behaviour of the human aortic arch during the bending and pressurisation test. The main motivation is to describe the material response of this artery when it is subjected to large quasi-static deformations in three different stages: bending, axial stretching and internal pressurisation. The sample corresponds to a young artery without cardiovascular pathologies. The pressure levels are within the normal and hypertension physiological ranges. The two principal findings of this work are firstly, the material characterisation performed via tensile test measurements that serve to derive the material parameters of a hyperelastic isotropic constitutive model and, secondly, the assessment of these material parameters in the simulation of the bending and pressurisation test. Overall, the reported material characterisation was found to provide a realistic description of the mechanical behaviour of the aortic arch under severe complex loading conditions considered in the bending and pressurisation test.

Mechanical characterisation of the human thoracic descending aorta: experiments and modelling.

This work presents experiments and modelling aimed at characterising the passive mechanical behaviour of the human thoracic descending aorta. To this end, uniaxial tension and pressurisation tests on healthy samples corresponding to newborn, young and adult arteries are performed. Then, the tensile measurements are used to calibrate the material parameters of the Holzapfel constitutive model. This model is found to adequately adjust the material behaviour in a wide deformation range; in particular, it captures the progressive stiffness increase and the anisotropy due to the stretching of the collagen fibres. Finally, the assessment of these material parameters in the modelling of the pressurisation test is addressed. The implication of this study is the possibility to predict the mechanical response of the human thoracic descending aorta under generalised loading states like those that can occur in physiological conditions and/or in medical device applications.

Factors influencing the mechanical behaviour of healthy human descending thoracic aorta.

In recent times, significant effort has been made to understand the mechanical behaviour of the arterial wall and how it is affected by the different vascular pathologies. However, to be able to interpret the results correctly, it is essential that the influence of other factors, such as aging or anisotropy, be understood. Knowledge of mechanical behaviour of the aorta has been customarily constrained by lack of data on fresh aortic tissue, especially from healthy young individuals. In addition, information regarding the point of rupture is also very limited. In this study, the mechanical behaviour of the descending thoracic aorta of 28 organ donors with no apparent disease, whose ages vary from 17 to 60 years, is evaluated. Tensile tests up to rupture are carried out to evaluate the influence of age and wall anisotropy. Results reveal that the tensile strength and stretch at failure of healthy descending aortas show a significant reduction with age, falling abruptly beyond the age of 30. This fact places age as a key factor when mechanical properties of descending aorta are considered.