Review

28 pages, 1795 KiB

Open AccessFeature PaperReview

Soft-Tissue Material Properties and Mechanogenetics during Cardiovascular Development

by Hummaira Banu Siddiqui, Sedat Dogru, Seyedeh Samaneh Lashkarinia and Kerem Pekkan

J. Cardiovasc. Dev. Dis. 2022, 9(2), 64; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd9020064 - 21 Feb 2022

Cited by 4 | Viewed by 3263

During embryonic development, changes in the cardiovascular microstructure and material properties are essential for an integrated biomechanical understanding. This knowledge also enables realistic predictive computational tools, specifically targeting the formation of congenital heart defects. Material characterization of cardiovascular embryonic tissue at consequent embryonic [...] Read more.

During embryonic development, changes in the cardiovascular microstructure and material properties are essential for an integrated biomechanical understanding. This knowledge also enables realistic predictive computational tools, specifically targeting the formation of congenital heart defects. Material characterization of cardiovascular embryonic tissue at consequent embryonic stages is critical to understand growth, remodeling, and hemodynamic functions. Two biomechanical loading modes, which are wall shear stress and blood pressure, are associated with distinct molecular pathways and govern vascular morphology through microstructural remodeling. Dynamic embryonic tissues have complex signaling networks integrated with mechanical factors such as stress, strain, and stiffness. While the multiscale interplay between the mechanical loading modes and microstructural changes has been studied in animal models, mechanical characterization of early embryonic cardiovascular tissue is challenging due to the miniature sample sizes and active/passive vascular components. Accordingly, this comparative review focuses on the embryonic material characterization of developing cardiovascular systems and attempts to classify it for different species and embryonic timepoints. Key cardiovascular components including the great vessels, ventricles, heart valves, and the umbilical cord arteries are covered. A state-of-the-art review of experimental techniques for embryonic material characterization is provided along with the two novel methods developed to measure the residual and von Mises stress distributions in avian embryonic vessels noninvasively, for the first time in the literature. As attempted in this review, the compilation of embryonic mechanical properties will also contribute to our understanding of the mature cardiovascular system and possibly lead to new microstructural and genetic interventions to correct abnormal development. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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15 pages, 1388 KiB

Open AccessReview

Mechanosensitive Pathways in Heart Development: Findings from Chick Embryo Studies

by Maha Alser, Samar Shurbaji and Huseyin C. Yalcin

J. Cardiovasc. Dev. Dis. 2021, 8(4), 32; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd8040032 - 26 Mar 2021

Cited by 9 | Viewed by 3733

Abstract

The heart is the first organ that starts to function in a developing embryo. It continues to undergo dramatic morphological changes while pumping blood to the rest of the body. Genetic regulation of heart development is partly governed by hemodynamics. Chick embryo is [...] Read more.

The heart is the first organ that starts to function in a developing embryo. It continues to undergo dramatic morphological changes while pumping blood to the rest of the body. Genetic regulation of heart development is partly governed by hemodynamics. Chick embryo is a major animal model that has been used extensively in cardiogenesis research. To reveal mechanosensitive pathways, a variety of surgical interferences and chemical treatments can be applied to the chick embryo to manipulate the blood flow. Such manipulations alter expressions of mechanosensitive genes which may anticipate induction of morphological changes in the developing heart. This paper aims to present different approaches for generating clinically relevant disturbed hemodynamics conditions using this embryonic chick model and to summarize identified mechanosensitive genes using the model, providing insights into embryonic origins of congenital heart defects. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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27 pages, 6837 KiB

Open AccessReview

Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease

by Huseyin Enes Salman and Huseyin Cagatay Yalcin

J. Cardiovasc. Dev. Dis. 2021, 8(2), 14; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd8020014 - 31 Jan 2021

Cited by 20 | Viewed by 5167

Abstract

The heart is the first functional organ in a developing embryo. Cardiac development continues throughout developmental stages while the heart goes through a serious of drastic morphological changes. Previous animal experiments as well as clinical observations showed that disturbed hemodynamics interfere with the [...] Read more.

The heart is the first functional organ in a developing embryo. Cardiac development continues throughout developmental stages while the heart goes through a serious of drastic morphological changes. Previous animal experiments as well as clinical observations showed that disturbed hemodynamics interfere with the development of the heart and leads to the formation of a variety of defects in heart valves, heart chambers, and blood vessels, suggesting that hemodynamics is a governing factor for cardiogenesis, and disturbed hemodynamics is an important source of congenital heart defects. Therefore, there is an interest to image and quantify the flowing blood through a developing heart. Flow measurement in embryonic fetal heart can be performed using advanced techniques such as magnetic resonance imaging (MRI) or echocardiography. Computational fluid dynamics (CFD) modeling is another approach especially useful when the other imaging modalities are not available and in-depth flow assessment is needed. The approach is based on numerically solving relevant physical equations to approximate the flow hemodynamics and tissue behavior. This approach is becoming widely adapted to simulate cardiac flows during the embryonic development. While there are few studies for human fetal cardiac flows, many groups used zebrafish and chicken embryos as useful models for elucidating normal and diseased cardiogenesis. In this paper, we explain the major steps to generate CFD models for simulating cardiac hemodynamics in vivo and summarize the latest findings on chicken and zebrafish embryos as well as human fetal hearts. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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18 pages, 12048 KiB

Open AccessFeature PaperReview

Angiogenesis in the Avian Embryo Chorioallantoic Membrane: A Perspective on Research Trends and a Case Study on Toxicant Vascular Effects

by Warren Burggren and Maria Rojas Antich

J. Cardiovasc. Dev. Dis. 2020, 7(4), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd7040056 - 05 Dec 2020

Cited by 9 | Viewed by 4040

Abstract

The chorioallantoic membrane (CAM) of the avian embryo is an intrinsically interesting gas exchange and osmoregulation organ. Beyond study by comparative biologists, however, the CAM vascular bed has been the focus of translational studies by cardiovascular life scientists interested in the CAM as [...] Read more.

The chorioallantoic membrane (CAM) of the avian embryo is an intrinsically interesting gas exchange and osmoregulation organ. Beyond study by comparative biologists, however, the CAM vascular bed has been the focus of translational studies by cardiovascular life scientists interested in the CAM as a model for probing angiogenesis, heart development, and physiological functions. In this perspective article, we consider areas of cardiovascular research that have benefited from studies of the CAM, including the themes of investigation of the CAM’s hemodynamic influence on heart and central vessel development, use of the CAM as a model vascular bed for studying angiogenesis, and the CAM as an assay tool. A case study on CAM vascularization effects of very low doses of crude oil as a toxicant is also presented that embraces some of these themes, showing the induction of subtle changes in the pattern of the CAM vasculature growth that are not readily observed by standard vascular assessment methodologies. We conclude by raising several questions in the area of CAM research, including the following: (1) Do changes in patterns of CAM growth, as opposed to absolute CAM growth, have biological significance?; (2) How does the relative amount of CAM vascularization compared to the embryo per se change during development?; and (3) Is the CAM actually representative of the mammalian systemic vascular beds that it is presumed to model? Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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19 pages, 3754 KiB

Open AccessEditor’s ChoiceReview

Embryonic Mouse Cardiodynamic OCT Imaging

by Andrew L. Lopez III, Shang Wang and Irina V. Larina

J. Cardiovasc. Dev. Dis. 2020, 7(4), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd7040042 - 04 Oct 2020

Cited by 9 | Viewed by 4803

Abstract

The embryonic heart is an active and developing organ. Genetic studies in mouse models have generated great insight into normal heart development and congenital heart defects, and suggest mechanical forces such as heart contraction and blood flow to be implicated in cardiogenesis and [...] Read more.

The embryonic heart is an active and developing organ. Genetic studies in mouse models have generated great insight into normal heart development and congenital heart defects, and suggest mechanical forces such as heart contraction and blood flow to be implicated in cardiogenesis and disease. To explore this relationship and investigate the interplay between biomechanical forces and cardiac development, live dynamic cardiac imaging is essential. Cardiodynamic imaging with optical coherence tomography (OCT) is proving to be a unique approach to functional analysis of the embryonic mouse heart. Its compatibility with live culture systems, reagent-free contrast, cellular level resolution, and millimeter scale imaging depth make it capable of imaging the heart volumetrically and providing spatially resolved information on heart wall dynamics and blood flow. Here, we review the progress made in mouse embryonic cardiodynamic imaging with OCT, highlighting leaps in technology to overcome limitations in resolution and acquisition speed. We describe state-of-the-art functional OCT methods such as Doppler OCT and OCT angiography for blood flow imaging and quantification in the beating heart. As OCT is a continuously developing technology, we provide insight into the future developments of this area, toward the investigation of normal cardiogenesis and congenital heart defects. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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18 pages, 2547 KiB

Open AccessReview

In Full Force. Mechanotransduction and Morphogenesis during Homeostasis and Tissue Regeneration

by Vasiliki Tsata and Dimitris Beis

J. Cardiovasc. Dev. Dis. 2020, 7(4), 40; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd7040040 - 01 Oct 2020

Cited by 10 | Viewed by 3918

Abstract

The interactions of form and function have been the focus of numerous studies in the context of development and more recently regeneration. Our understanding on how cells, tissues and organs sense and interpret external cues, such as mechanical forces, is becoming deeper as [...] Read more.

The interactions of form and function have been the focus of numerous studies in the context of development and more recently regeneration. Our understanding on how cells, tissues and organs sense and interpret external cues, such as mechanical forces, is becoming deeper as novel techniques in imaging are applied and the relevant signaling pathways emerge. These cellular responses can be found from bacteria to all multicellular organisms such as plants and animals. In this review, we focus on hemodynamic flow and endothelial shear stress during cardiovascular development and regeneration, where the interactions of morphogenesis and proper function are more prominent. In addition, we address the recent literature on the role of extracellular matrix and fibrotic response during tissue repair and regeneration. Finally, we refer to examples where the integration of multi-disciplinary approaches to understand the biomechanics of cellular responses could be utilized in novel medical applications. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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31 pages, 8409 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease

by Bradley B. Keller, William J. Kowalski, Joseph P. Tinney, Kimimasa Tobita and Norman Hu

J. Cardiovasc. Dev. Dis. 2020, 7(2), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd7020023 - 12 Jun 2020

Cited by 9 | Viewed by 3877

Abstract

The goal of this review is to provide a broad overview of the biomechanical maturation and regulation of vertebrate cardiovascular (CV) morphogenesis and the evidence for mechanistic relationships between function and form relevant to the origins of congenital heart disease (CHD). The embryonic [...] Read more.

The goal of this review is to provide a broad overview of the biomechanical maturation and regulation of vertebrate cardiovascular (CV) morphogenesis and the evidence for mechanistic relationships between function and form relevant to the origins of congenital heart disease (CHD). The embryonic heart has been investigated for over a century, initially focusing on the chick embryo due to the opportunity to isolate and investigate myocardial electromechanical maturation, the ability to directly instrument and measure normal cardiac function, intervene to alter ventricular loading conditions, and then investigate changes in functional and structural maturation to deduce mechanism. The paradigm of “Develop and validate quantitative techniques, describe normal, perturb the system, describe abnormal, then deduce mechanisms” was taught to many young investigators by Dr. Edward B. Clark and then validated by a rapidly expanding number of teams dedicated to investigate CV morphogenesis, structure–function relationships, and pathogenic mechanisms of CHD. Pioneering studies using the chick embryo model rapidly expanded into a broad range of model systems, particularly the mouse and zebrafish, to investigate the interdependent genetic and biomechanical regulation of CV morphogenesis. Several central morphogenic themes have emerged. First, CV morphogenesis is inherently dependent upon the biomechanical forces that influence cell and tissue growth and remodeling. Second, embryonic CV systems dynamically adapt to changes in biomechanical loading conditions similar to mature systems. Third, biomechanical loading conditions dynamically impact and are regulated by genetic morphogenic systems. Fourth, advanced imaging techniques coupled with computational modeling provide novel insights to validate regulatory mechanisms. Finally, insights regarding the genetic and biomechanical regulation of CV morphogenesis and adaptation are relevant to current regenerative strategies for patients with CHD. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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26 pages, 5561 KiB

Open AccessEditor’s ChoiceReview

Follow Me! A Tale of Avian Heart Development with Comparisons to Mammal Heart Development

by Rusty Lansford and Sandra Rugonyi

J. Cardiovasc. Dev. Dis. 2020, 7(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/jcdd7010008 - 07 Mar 2020

Cited by 7 | Viewed by 7056

Abstract

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can [...] Read more.

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can then be covered, and the embryo returned to the incubator for the desired amount of time, and observed during further development. Up to about 4 days of chicken development (out of 21 days of incubation), when the egg is opened the embryo is on top of the yolk, and its heart is on top of its body. This allows easy imaging of heart formation and heart development using non-invasive techniques, including regular optical microscopy. After day 4, the embryo starts sinking into the yolk, but still imaging technologies, such as ultrasound, can tomographically image the embryo and its heart in vivo. Importantly, because like the human heart the avian heart develops into a four-chambered heart with valves, heart malformations and pathologies that human babies suffer can be replicated in avian embryos, allowing a unique developmental window into human congenital heart disease. Here, we review avian heart formation and provide comparisons to the mammalian heart. Full article

(This article belongs to the Special Issue Comparative Developmental Cardiovascular Biomechanics and Bioengineering)

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