Showing papers by "Gerhard Holzapfel published in 2022"
TL;DR: The results show the importance of VSM activation on the static and dynamic mechanical response of human aortas and provide material data and a material model for the development of a future generation of active aortic grafts that mimic natural behavior and help regulate blood pressure.
Abstract: Significance The rupture of aortic aneurysms causes around 10,000 deaths each year in the United States. Prosthetic tubes for aortic repair present a large mismatch of mechanical properties with the natural aorta, which has negative consequences for perfusion. This motivates research into the mechanical characterization of human aortas to develop a new generation of mechanically compatible aortic grafts. Experimental data and a suitable material model for human aortas with vascular smooth muscle (VSM) activation are not available. Hence, the present study provides experimental data that are needed. These data made it possible to develop a precise structure-based model of active aortic tissue. The results show the importance of VSM activation on the static and dynamic mechanical response of human aortas. Experimental data and a suitable material model for human aortas with smooth muscle activation are not available in the literature despite the need for developing advanced grafts; the present study closes this gap. Mechanical characterization of human descending thoracic aortas was performed with and without vascular smooth muscle (VSM) activation. Specimens were taken from 13 heart-beating donors. The aortic segments were cooled in Belzer UW solution during transport and tested within a few hours after explantation. VSM activation was achieved through the use of potassium depolarization and noradrenaline as vasoactive agents. In addition to isometric activation experiments, the quasistatic passive and active stress–strain curves were obtained for circumferential and longitudinal strips of the aortic material. This characterization made it possible to create an original mechanical model of the active aortic material that accurately fits the experimental data. The dynamic mechanical characterization was executed using cyclic strain at different frequencies of physiological interest. An initial prestretch, which corresponded to the physiological conditions, was applied before cyclic loading. Dynamic tests made it possible to identify the differences in the viscoelastic behavior of the passive and active tissue. This work illustrates the importance of VSM activation for the static and dynamic mechanical response of human aortas. Most importantly, this study provides material data and a material model for the development of a future generation of active aortic grafts that mimic natural behavior and help regulate blood pressure.
14 citations
TL;DR: In this article , the authors used second harmonic generation (SHG) microscopy in combination with planar biaxial mechanical tests to better model and examine collagen fibers and mechanical properties of mitral valve (MV) leaflets.
10 citations
TL;DR: Methods are being developed in order to efficiently determine the waviness, that is, tortuosity and amplitude, as well as the diameter, orientation, and dispersion of collagen fibers, and bundles in healthy and aneurysmal tissues.
Abstract: Abstract Collagen plays a key role in the strength of aortic walls, so studying micro-structural changes during disease development is critical to better understand collagen reorganization. Second-harmonic generation microscopy is used to obtain images of human aortic collagen in both healthy and diseased states. Methods are being developed in order to efficiently determine the waviness, that is, tortuosity and amplitude, as well as the diameter, orientation, and dispersion of collagen fibers, and bundles in healthy and aneurysmal tissues. The results show layer-specific differences in the collagen of healthy tissues, which decrease in samples of aneurysmal aortic walls. In healthy tissues, the thick collagen bundles of the adventitia are characterized by greater waviness, both in the tortuosity and in the amplitude, compared to the relatively thin and straighter collagen fibers of the media. In contrast, most aneurysmal tissues tend to have a more uniform structure of the aortic wall with no significant difference in collagen diameter between the luminal and abluminal layers. An increase in collagen tortuosity compared to the healthy media is also observed in the aneurysmal luminal layer. The data set provided can help improve related material and multiscale models of aortic walls and aneurysm formation.
8 citations
TL;DR: In this paper , the arrangement of collagen fibrils and proteoglycans (PGs) within the mechanically loaded aortic wall was investigated using convolutional neural networks.
6 citations
TL;DR: CANN as discussed by the authors proposes a neural network based approach to automatically discover the best model and parameters to explain experimental data, which is translated into a complex non-convex optimization problem.
Abstract: Choosing the best constitutive model and the right set of model parameters is at the heart of continuum mechanics. For decades, the gold standard in constitutive modeling has been to first select a model and then fit its parameters to data. However, the success of this approach is highly dependent on user experience and personal preference. Here we propose a new method that simultaneously and fully autonomously discovers the best model and parameters to explain experimental data. Mathematically, the model finding is translated into a complex non-convex optimization problem. We solve this problem by formulating it as a neural network, and leveraging the success, robustness, and stability of the optimization tools developed in classical neural network modeling. Instead of using a classical off-the-shelf neural network, we design a new family of Constitutive Artificial Neural Networks with activation functions that feature popular constitutive models and parameters that have a clear physical interpretation. Our new network inherently satisfies general kinematic, thermodynamic, and physical constraints and trains robustly, even with sparse data. We illustrate its potential for biaxial extension experiments on skin and demonstrate that the majority of network weights train to zero, while the small subset of non-zero weights defines the discovered model. Unlike classical network weights, these weights are physically interpretable and translate naturally into engineering parameters and microstructural features such as stiffness and fiber orientation. Our results suggest that Constitutive Artificial Neural Networks enable automated model, parameter, and experiment discovery and could initiate a paradigm shift in constitutive modeling, from user-defined to automated model selection and parameterization. Our source code, data, and examples are available at https://github.com/LivingMatterLab/CANN.
6 citations
5 citations
TL;DR: Comparison of topographical and biomechanical properties of cRBC, generated from human CD34+ adult hematopoietic stem/progenitor cells, with native reticulocytes (nRET) and erythrocytes (nRBC), showed a high similarity between cR BC and nRBC.
Abstract: Modern medicine increases the demand for safe blood products. Ex vivo cultured red blood cells (cRBC) are eagerly awaited as a standardized, safe source of RBC. Established culture models still lack the terminal cytoskeletal remodeling from reticulocyte to erythrocyte with changes in the biomechanical properties and interacts with membrane stiffness, viscosity of the cytoplasm and the cytoskeletal network. Comprehensive data on the biomechanical properties of cRBC are needed to take the last step towards translation into clinical use in transfusion medicine. Aim of the study was the comparative analysis of topographical and biomechanical properties of cRBC, generated from human CD34+ adult hematopoietic stem/progenitor cells, with native reticulocytes (nRET) and erythrocytes (nRBC) using cell biological and biomechanical technologies. To gain the desired all-encompassing information, a single method was unsatisfactory and only the combination of different methods could lead to the goal. Topographical information was matched with biomechanical data from optical tweezers (OT), atomic force microscopy (AFM) and digital holographic microscopy (DHM). Underlying structures were investigated in detail. Imaging, deformability and recovery time showed a high similarity between cRBC and nRBC. Young’s modulus and plasticity index also confirmed this similarity. No significant differences in membrane and cytoskeletal proteins were found, while lipid deficiency resulted in spherical, vesiculated cells with impaired biomechanical functionality. The combination of techniques has proven successful and experiments underscore a close relationship between lipid content, shape and biomechanical functionality of RBC.
2 citations
TL;DR: In this paper , a recent mechanopathological theory, which correlates abdominal aortic aneurysms progression with microstructural and mechanical alterations in the tissue, is investigated using multiscale models.
2 citations
TL;DR: In this article , a stochastic constitutive model was proposed to model the degradation of interlamellar elastic fibers in the dissected aortic wall and a convolutional neural network was used as a surrogate model that maps the random input fields to the output stress distribution obtained from the finite element analysis.
2 citations
TL;DR: In this article , the electrical transport properties of REBa2Cu3O7−δ nanocomposite films were investigated using transmission electron microscopy and transport measurements in magnetic fields up to 24 T. The optimization process of the crystallization step (temperature and oxygen partial pressure) as well as an aging effect, which is due to the release of trapped fluorine, were described.
Abstract: In order to improve the electrical transport properties of REBa2Cu3O7−δ nanocomposite films, SmBa2Cu3O7−δ films with and without BaHfO3 nanoparticles were grown by chemical solution deposition, and their microstructural and transport properties were investigated in a detailed study using transmission electron microscopy and transport measurements in magnetic fields up to 24 T. The optimization process of the crystallization step (temperature and oxygen partial pressure) as well as an aging effect, which is due to the release of trapped fluorine, are described. Critical temperature and critical current densities surprisingly improve initially during the aging. Due to the complex microstructure, the additional BaHfO3 nanoparticles have only a positive effect at low magnetic fields for our samples.
2 citations
TL;DR: In this article , a hybrid machine learning (HML) method was proposed for surrogate modeling of soft tissues with complex multi-physics properties in small data regimes, which can improve training convergence for very limited training samples.
TL;DR: For the first time, structural parameters of human aortic tissue under continuous loading conditions have been obtained and waviness parameters at the reference configuration have been associated with tissue stiffness, brittleness, and the onset of atherosclerosis.
TL;DR: The results show that all the three tricuspid valve leaflets shrink after explant from the ex vivo heart, and the strains observed after dissection of the central 10×10 mm region of the leaflet are smaller than when the valve is explanted, suggesting that the strained tissues are mainly due to the release of in situ annulus and chordae connections.
TL;DR: In this article , the authors take up the swelling polymer theory and couples the swelling behavior of GAGs/proteoglycans with the anisotropic response of aortic tissues in order to investigate the initiation mechanism of Aortic dissection.
Abstract: Abstract Aortic dissection is a life-threatening pathology that mainly affects the medial layer, which consists of multiple lamellar units. Glycosaminoglycans/proteoglycans (GAGs/PGs) can accumulate in the interlamellar space within the media and under certain circumstances swell considerably. Such behavior of GAGs/PGs induces high stresses in the elements connecting the elastic laminae and, in the event of tissue failure, leads to medial delamination and thus to the initiation of aortic dissection. The present study takes up the swelling polymer theory and couples the swelling behavior of GAGs/PGs with the anisotropic response of aortic tissues in order to investigate the initiation mechanism of aortic dissection. The computational simulation uses an advanced weighted constitutive model, which is combined with the global and submodel technique in the finite element software Abaqus. The numerical results show that the proposed method is able to generate failure stresses of the same order of magnitude as the failure stresses indicated in tensile tests. Stress concentrations are observed at the connection between interlamellar struts made of elastic fibers and elastic laminae. Such connections are hotspots at which dissections are expected to initiate. Therefore, this study presents the prediction of the onset of aortic dissection due to the accumulation and swelling of GAGs/PGs and provides a solid foundation for future modeling work.
TL;DR: In this article , the first CSD-grown high-entropy (HE) REBCO nanocomposite was successfully synthesized and the X-ray reaction patterns showed a near-perfect c-axis oriented grain growth.
Abstract: High-entropy oxide (HEO) superconductors have been developed since very recently. Di ff erent superconductors can be produced in the form of a high-entropy compound, including REBa 2 Cu 3 O 7 − d (REBCO). However, until now, mainly bulk samples (mostly in polycrystalline form) have been reported. In this work, the fi rst CSD-grown high-entropy (HE) REBCO nanocomposite fi lms were successfully synthesized. In particular, high-quality Gd 0.2 Dy 0.2 Y 0.2 Ho 0.2 Er 0.2 Ba 2 Cu 3 O 7 − d nanocomposite fi lms with 12 mol% BaHfO 3 nanoparticles were grown on SrTiO 3 substrates. The X-ray di ff raction patterns show a near-perfect c -axis oriented grain growth. Both T c and 77 K J sfc , 91.9 K and 3.5 MA cm − 2 , respectively, are comparable with the values of the single-RE REBCO fi lms. Moreover, at low temperatures, speci fi cally at 30 K, the J c values are larger than those of the single-RE samples. A transmission electron microscopy (TEM) study, including energy-dispersive X-ray spectroscopy (EDXS) measurements, reveals that the di ff erent RE 3+ ions are distributed homogeneously in the matrix without forming clusters. This distribution causes point-like pinning centres that explain the superior performances of these samples at low temperatures. Although still seen as a proof-of-concept for the feasibility of preparing such fi lms, these results demonstrate that the HE REBCO fi lms are a promising option for the future fabrication of high-performance coated conductors. In the investigated B – T range, however, their J c values are still lower than those of other, medium-entropy REBCO fi lms, which shows that an optimization of the composition of the HE REBCO fi lms is needed to maximize their performance.
22 Feb 2022
TL;DR: This work developed the first automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development at low balloon pressure in a rabbit model of atherosclerosis, and used this system to investigate the risk factor interplay.
Abstract:
Atherosclerosis is the leading cause of cardiovascular disease, which is responsible for the majority of deaths worldwide. Lack of reproducible and controlled induction of atherosclerotic lesions in preclinical animal models limits atherosclerosis research. Here, we developed the first automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development at low balloon pressure in a rabbit model of atherosclerosis, and used this system to investigate the risk factor interplay. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. Already in the absence of hypercholesterolemia, deficiency in vitamins and choline required for homocysteine metabolization results in atherogenic transformation of the aorta i.e. impairment of its biomechanical properties, alteration of collagen organization as well as macrophage and lipid accumulation, and aggravation of atherosclerosis including significantly altered water diffusion and impaired vascular reactivity in its presence.
TL;DR: In this article , the authors take up the swelling polymer theory and couples the swelling behavior of GAGs/proteoglycans with the anisotropic response of aortic tissues in order to investigate the initiation mechanism of Aortic dissection.
Abstract: Abstract Aortic dissection is a life-threatening pathology that mainly affects the medial layer, which consists of multiple lamellar units. Glycosaminoglycans/proteoglycans (GAGs/PGs) can accumulate in the interlamellar space within the media and under certain circumstances swell considerably. Such behavior of GAGs/PGs induces high stresses in the elements connecting the elastic laminae and, in the event of tissue failure, leads to medial delamination and thus to the initiation of aortic dissection. The present study takes up the swelling polymer theory and couples the swelling behavior of GAGs/PGs with the anisotropic response of aortic tissues in order to investigate the initiation mechanism of aortic dissection. The computational simulation uses an advanced weighted constitutive model, which is combined with the global and submodel technique in the finite element software Abaqus. The numerical results show that the proposed method is able to generate failure stresses of the same order of magnitude as the failure stresses indicated in tensile tests. Stress concentrations are observed at the connection between interlamellar struts made of elastic fibers and elastic laminae. Such connections are hotspots at which dissections are expected to initiate. Therefore, this study presents the prediction of the onset of aortic dissection due to the accumulation and swelling of GAGs/PGs and provides a solid foundation for future modeling work.
TL;DR: In this paper , the first CSD-grown high-entropy (HE) REBCO nanocomposite was successfully synthesized and the X-ray reaction patterns showed a near-perfect c-axis oriented grain growth.
Abstract: High-entropy oxide (HEO) superconductors have been developed since very recently. Di ff erent superconductors can be produced in the form of a high-entropy compound, including REBa 2 Cu 3 O 7 − d (REBCO). However, until now, mainly bulk samples (mostly in polycrystalline form) have been reported. In this work, the fi rst CSD-grown high-entropy (HE) REBCO nanocomposite fi lms were successfully synthesized. In particular, high-quality Gd 0.2 Dy 0.2 Y 0.2 Ho 0.2 Er 0.2 Ba 2 Cu 3 O 7 − d nanocomposite fi lms with 12 mol% BaHfO 3 nanoparticles were grown on SrTiO 3 substrates. The X-ray di ff raction patterns show a near-perfect c -axis oriented grain growth. Both T c and 77 K J sfc , 91.9 K and 3.5 MA cm − 2 , respectively, are comparable with the values of the single-RE REBCO fi lms. Moreover, at low temperatures, speci fi cally at 30 K, the J c values are larger than those of the single-RE samples. A transmission electron microscopy (TEM) study, including energy-dispersive X-ray spectroscopy (EDXS) measurements, reveals that the di ff erent RE 3+ ions are distributed homogeneously in the matrix without forming clusters. This distribution causes point-like pinning centres that explain the superior performances of these samples at low temperatures. Although still seen as a proof-of-concept for the feasibility of preparing such fi lms, these results demonstrate that the HE REBCO fi lms are a promising option for the future fabrication of high-performance coated conductors. In the investigated B – T range, however, their J c values are still lower than those of other, medium-entropy REBCO fi lms, which shows that an optimization of the composition of the HE REBCO fi lms is needed to maximize their performance.
TL;DR: In this article , the first CSD-grown high-entropy (HE) REBCO nanocomposite films were successfully synthesized and the X-ray diffraction patterns showed a near-perfect c-axis oriented grain growth.
Abstract: High-entropy oxide (HEO) superconductors have been developed since very recently. Different superconductors can be produced in the form of a high-entropy compound, including REBa2Cu3O7−δ (REBCO). However, until now, mainly bulk samples (mostly in polycrystalline form) have been reported. In this work, the first CSD-grown high-entropy (HE) REBCO nanocomposite films were successfully synthesized. In particular, high-quality Gd0.2Dy0.2Y0.2Ho0.2Er0.2Ba2Cu3O7−δ nanocomposite films with 12 mol% BaHfO3 nanoparticles were grown on SrTiO3 substrates. The X-ray diffraction patterns show a near-perfect c-axis oriented grain growth. Both Tc and 77 K Jsfc, 91.9 K and 3.5 MA cm−2, respectively, are comparable with the values of the single-RE REBCO films. Moreover, at low temperatures, specifically at 30 K, the Jc values are larger than those of the single-RE samples. A transmission electron microscopy (TEM) study, including energy-dispersive X-ray spectroscopy (EDXS) measurements, reveals that the different RE3+ ions are distributed homogeneously in the matrix without forming clusters. This distribution causes point-like pinning centres that explain the superior performances of these samples at low temperatures. Although still seen as a proof-of-concept for the feasibility of preparing such films, these results demonstrate that the HE REBCO films are a promising option for the future fabrication of high-performance coated conductors. In the investigated B–T range, however, their Jc values are still lower than those of other, medium-entropy REBCO films, which shows that an optimization of the composition of the HE REBCO films is needed to maximize their performance.
TL;DR: The present study characterizes the unique regional mechanical and microstructural properties of the porcine left anterior descending artery using biaxial testing, polarized-light imaging, and confocal microscopy and provides an improved understanding of the collagen/elastin architecture in response to mechanical loads using a regionspecific approach.
Abstract: Coronary atherosclerosis is the main cause of death worldwide. Advancing the understanding of coronary microstructure-based mechanics is fundamental for the development of therapeutic tools and surgical procedures. Although the passive biaxial properties of the coronary arteries have been extensively explored, their regional differences and the relationship between tissue microstructure and mechanics have not been fully characterized. In this study, we characterized the passive biaxial mechanical properties and microstructural properties of the proximal, medial, and distal regions of the porcine left anterior descending artery (LADA). We also attempted to relate the biaxial stress-stretch response of the LADA and its respective birefringent responses to the polarized light for obtaining information about the load-dependent microstructural variations. We found that the LADA extensibility is reduced in the proximal-to-distal direction and that the medial region exhibits more heterogeneous mechanical behavior than the other two regions. We have also observed highly dynamic microstructural behavior where fiber families realign themselves depending on loading. In addition, we found that the microstructure of the distal region exhibited highly aligned fibers along the longitudinal axis of the artery. To verify this microstructural feature, we imaged the LADA specimens with multi-photon microscopy and observed that the adventitia microstructure transitioned from a random fiber network in the proximal region to highly aligned fibers in the distal region. Our findings may offer new perspectives for understanding coronary mechanics and aid in the development of tissue-engineered vascular grafts, which are currently limited due to their mismatch with native tissue in terms of mechanical properties and microstructural features. STATEMENT OF SIGNIFICANCE: The tissue biomechanics of coronary arteries is fundamental for the development of revascularization techniques such as coronary artery bypass. These therapeutics require a deep understanding of arterial mechanics, microstructure, and mechanobiology to prevent graft failure and reoperation. The present study characterizes the unique regional mechanical and microstructural properties of the porcine left anterior descending artery using biaxial testing, polarized-light imaging, and confocal microscopy. This comprehensive characterization provides an improved understanding of the collagen/elastin architecture in response to mechanical loads using a regionspecific approach. The unique tissue properties obtained from this study will provide guidance for the selection of anastomotic sites in coronary artery bypass grafting and for the design of tissue-engineered vascular grafts.
TL;DR: In this article , the impact of rare-earth stoichiometry on the structure and superconducting properties of YGBCO-BHO nanocomposite was investigated.
Abstract: —Y 1- x Gd x Ba 2 Cu 3 O 7 -BaHfO 3 (YGBCO-BHO) nanocomposite films containing 12 mol% BHO nanoparticles and different amounts of Gd, x , were grown by Chemical Solution Deposition (CSD) on Ni5W substrates in order to investigate the impact of the rare-earth stoichiometry on the structure and superconducting properties of these films. For Gd contents x > 0.5, epitaxial YGBCO-BHO films with an approximate thickness of 270 nm self-field critical current density J c at 77 K ∼ 1,5 MA/cm² were obtained. The field dependence of the critical current density J c ( B ) shows a much larger accommodation field and lower exponents α in J c ∼ B − α values compared to pristine YBCO films. This is both due to the high amount of individual nanoparticles in the matrix as observed in TEM images and the higher critical temperatures T c . The results show that the CSD is a potential candidate for the preparation of RE BCO films in long-length coated conductors.
05 Sep 2022
TL;DR: This article showed that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin.
Abstract: Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors, including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in vivo models of atherosclerosis that resemble the human situation. Here, we have developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development, even at low balloon pressure. Our automated system helped to glean vital details of cholesterol-independent changes in the aortic wall of balloon-injured rabbits. We show that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin in the absence of hypercholesterolemia. A combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity compared to any single condition. Our findings suggest that deficiency of B vitamins leads to atherogenic transformation of the aorta even in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.