Publications by authors named "Gerhard A Holzapfel"

Computational modeling has become an integral tool for understanding the interaction between structural organization and functional behavior in a wide range of biological tissues, including the human myocardium. Traditional constitutive models, and recent models generated by automated model discovery, are often based on the simplifying assumption of perfectly aligned fiber families. However, experimental evidence suggests that many fiber-reinforced tissues exhibit local dispersion, which can significantly influence their mechanical behavior.

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Introduction: Protocols for tissue clearing have been established and optimized for the central nervous system. However, significant modifications are required for clearing different tissue types. Therefore, effective optical clearing for cardiovascular tissue remains a major challenge.

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Biodegradable polymeric scaffolds produced by electrospinning offer an innovative alternative to conventional implants made from animal or synthetic materials. By promoting endogenous tissue restoration (ETR), these scaffolds solve problems such as limited durability, calcification, and thromboembolic complications. The concept of ETR is based on the idea that a biodegradable scaffold provides temporary structural support until it is gradually replaced by the body's own tissue through natural regeneration processes.

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Atherosclerotic arteries exhibit geometric alterations due to plaque deposition, which often leads to luminal narrowing. Balloon angioplasty is a common and suggested treatment to restore blood flow. However, depending on balloon oversizing, rupture at the plaque shoulder or the fibrous cap may occur.

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Hyperhomocysteinemia, an elevated level of homocysteine in the blood, is an independent risk factor for atherosclerosis and, more generally, cardiovascular disease. However, its relationship with aortic biomechanics has not been investigated yet. To better understand the influence of elevated homocysteine levels on aortic biomechanics, we propose an animal model in which hyperhomocysteinemia, hypercholesterolemia, and their combination were induced in rabbits by balloon injury of the abdominal aorta, special diets, and intravenous homocysteine injections.

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Personalized computational simulations have emerged as a vital tool to understand the biomechanical factors of a disease, predict disease progression, and design personalized intervention. Material modeling is critical for realistic biomedical simulations, and poor model selection can have life-threatening consequences for the patient. However, selecting the best model requires a profound domain knowledge and is limited to a few highly specialized experts in the field.

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Tissue decellularization has emerged as a technique to provide an acellular, non-immunogenic scaffold that preserves the morphological features of native tissue. To study the possible effects of decellularization, investigating the mechanical behavior and the protein composition is crucial. In this study, we performed extension-inflation tests on native and decellularized porcine vena cava and investigated their microstructure using multiphoton microscopy.

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Modeling of subcutaneous adipose tissue (SAT) plays an important role in forensic biomechanics as blunt force trauma represents one of the most common types of injury. To better understand the involved injury mechanisms, a material model is needed that can (i) represent realistic behavior for combined loading scenarios and (ii) consider the microstructure of the SAT. Therefore, a SAT model was developed that consists of two parts for the strain-energy function - a neo-Hookean part representing the adipocytes and a part representing the surrounding reinforced basement membrane, which is modeled via three circular fiber families oriented in the three main planes, resulting in isotropic model behavior.

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The prevalence of gastric problems, which are associated with high economic costs and medical complexity, is soaring worldwide. In biomedical research, porcine models have been widely used to investigate the gastrointestinal tract in preclinical studies due to their similar functionality and macrostructure. Despite their widespread acceptance, there is insufficient research on whether porcine gastric tissue accurately reflects the biomechanics and microstructure of the human stomach.

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In the context of numerical simulations of the vascular system, local geometric uncertainties have not yet been examined in sufficient detail due to model complexity and the associated large numerical effort. Such uncertainties are related to geometric modeling errors resulting from computed tomography imaging, segmentation and meshing. This work presents a methodology to systematically induce local modifications and perform a sufficient number of blood flow simulations to draw statistically relevant conclusions on the most commonly employed quantities of interest, such as flow rates or wall shear stress.

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Soft scaffold materials for cell cultures grafted onto the chorioallantoic membrane (CAM) provide innovative solutions for creating physiologically relevant environments by mimicking the host tissue. Biocompatible hydrogels represent an ideal medium for such applications, but the relationship between scaffold mechanical properties and reactions at the biological interface remains poorly understood. This study examines the attachment and integration of soft hydrogels on the CAM using an accessible system.

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The human body consists of many different soft biological tissues that exhibit diverse microstructures and functions and experience diverse loading conditions. Yet, under many conditions, the mechanical behaviour of these tissues can be described well with similar nonlinearly elastic or inelastic constitutive relations, both in health and some diseases. Such constitutive relations are essential for performing nonlinear stress analyses, which in turn are critical for understanding physiology, pathophysiology and even clinical interventions, including surgery.

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Aortic dissection continues to be responsible for significant morbidity and mortality, although recent advances in medical data assimilation and in experimental and models have improved our understanding of the initiation and progression of the accumulation of blood within the aortic wall. Hence, there remains a pressing necessity for innovative and enhanced models to more accurately characterize the associated pathological changes. Early on, experimental models were employed to uncover mechanisms in aortic dissection, such as hemodynamic changes and alterations in wall microstructure, and to assess the efficacy of medical implants.

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During gastric surgery, the stomach wall is compressed with clamps and sutures or staple lines. These short- and long-term deformations can severely compromise the integrity of the tissue and make it difficult for the stomach wall to respond and remodel to the new loading conditions. Consequently, serious intra- and postoperative complications such as the formation of leaks during bariatric surgeries, can be associated with these immense tissue deformations.

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This study aims to assess the outcomes of therapeutic options for aortic arch pathologies by comparing thoracic endovascular aortic repair (TEVAR) with open arch replacement (OAR) using woven polyester grafts from a mechanical and biomechanical perspective, with emphasis on ex vivo perfused human thoracic aortas reproducing heart rate and stroke volume conditions. Eleven non-diseased thoracic aortas from human cadavers were divided into TEVAR (n=5) and OAR (n=6) and tested using a custom-built mock circulation loop. Pressure, diameter, and stroke volume were monitored during perfusion before and after the intervention.

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The brain is arguably the most complex human organ and modelling its mechanical behaviour has challenged researchers for decades. There is still a lack of understanding on how this multiphase tissue responds to mechanical loading and how material parameters can be reliably calibrated. While previous viscoelastic models with two relaxation times have successfully captured the response of brain tissue, the Theory of Porous Media provides a continuum mechanical framework to explore the underlying physical mechanisms, including interactions between solid matrix and free-flowing interstitial fluid.

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The hemodynamic and convective heat transfer effects of a patient-specific endovascular therapeutic agent based on shape-memory polymer foam (SMPf) are evaluated using computational fluid dynamics studies for six patient-specific aneurysm geometries. The SMPf device is modeled as a continuous porous medium with full expansion for the flow studies and with various degrees of expansion for the heat transfer studies. The flow simulation parameters were qualitatively validated based on the existing literature.

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Computational fluid dynamics (CFD) simulations have been introduced to enable individualized risk prognosis for patients with unruptured cerebral aneurysms. The present contribution provides an overview of the biomechanical and physiological principles of aneurysm formation and rupture. It describes the computational steps of the CFD and the evaluated parameters.

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Aortic dissection leads to late complications due tochronic degeneration and dilatation of the false lumen. This study examines the interaction between hemodynamics and long-term remodeling of a patient's aortic dissection, tracked from pre-dissection to the chronic phase using CT angiography. Fluid-structure interaction models with tissue prestress, external support, and anisotropic properties were used to analyze hemodynamic markers.

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The evolution of arterial biomechanics and microstructure with age and disease plays a critical role in understanding the health and function of the cardiovascular system. Accurately capturing these adaptative processes and their effects on the mechanical environment is critical for predicting arterial responses. This challenge is exacerbated by the significant differences between elastic and muscular arteries, which have different structural organizations and functional demands.

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Article Synopsis
  • * A study showed that rabbits lacking B vitamins experienced significant vascular damage when given Hcy, despite low cholesterol levels, including issues like collagen disorganization and impaired vascular reactivity.
  • * Findings indicate that Hcy promotes atherogenic changes in the aorta, suggesting its harmful effects extend beyond just high cholesterol conditions.
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Advanced numerical simulations of the mechanical behavior of human skin require thorough calibration of the material's constitutive models based on experimental ex vivo mechanical tests along with images of tissue microstructure for a variety of biomedical applications. In this work, a total of 14 human healthy skin samples and 4 additional scarred skin samples were experimentally analyzed to gain deep insights into the biomechanics of human skin. In particular, second harmonic generation (SHG) microscopy was used to extract detailed images of the distribution of collagen fibers, which were subsequently processed using a three-dimensional Fourier transform-based method recently proposed by the authors to quantify the distribution of fiber orientations.

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Brain disorders represent an ever-increasing health challenge worldwide. While conventional drug therapies are less effective due to the presence of the blood-brain barrier, infusion-based methods of drug delivery to the brain represent a promising option. Since these methods are mechanically controlled and involve multiple physical phases ranging from the neural and molecular scales to the brain scale, highly efficient and precise delivery procedures can significantly benefit from a comprehensive understanding of drug-brain and device-brain interactions.

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Degenerative mitral valve disease is a common valvular disease with two arguably distinct phenotypes: fibroelastic deficiency and Barlow's disease. These phenotypes significantly alter the microstructures of the leaflets, particularly the collagen fibers, which are the main mechanical load carriers. The predominant method of investigation is histological sections.

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On needs-based ex vivo monitoring of implantable devices or tissues/organs in cardiovascular simulators provides new insights and paves new paths for device prototypes. The insights gained could not only support the needs of patients, but also inform engineers, scientists and clinicians about undiscovered aspects of diseases (during routine monitoring). We analyze seminal and current work and highlight a variety of opportunities for developing preclinical tools that would improve strategies for future implantable devices.

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