This volume of the series Cardiac and Vascular Biology presents the most relevant aspects of vascular mechanobiology along with many more facets of this fascinating, timely and clinically highly relevant field. Mechanotransduction, mechanosensing, fluid shear stress, hameodynamics and cell fate, are just a few topics to name. All important aspects of vascular mechanobiology in health and disease are reviewed by some of the top experts in the field. This volume, together with a second title on cardiac mechanobiology featured in this series, will be of high relevance to scientists and clinical researchers in the area of vascular biology, cardiology and biomedical engineering.

Biomechanical forces play a major role in organ development, shape and function. When exceeding the physiological range, however, they may become detrimental for organ structure and function. This is probably best exemplified by the cardiovascular system, with both the heart and blood vessels being continuously exposed to the biomechanical forces exerted by the flow of blood. In the heart, it is the build-up of pressure inside the ventricles that allows the ejection of blood into the pulmonary and systemic circulation. The luminal diameter of the small arteries in both parts of the circulation determines the resistance to flow. Hence it also determines the level of blood pressure in both the pulmonary and systemic circulation and thus the afterload for both ventricles of the heart. A narrowing of the small arteries (e.g. due to an increase in tone) therefore leads to an increase in blood pressure in the affected part of the circulation. This will decrease organ perfusion but increase the afterload for the corresponding ventricle of the heart. Consequently, the affected ventricle must build up more pressure to maintain cardiac output. However, if the rise in blood pressure (pulmonary or arterial hypertension) persists the increase in wall tension can no longer be compensated by active constriction, thereby forcing the ventricle to resort to other means to unload itself. Typically, this is achieved by structural alterations in its wall which becomes thicker (hypertrophy) and stiffer (remodelling of the extracellular matrix). Ultimately, this maladaptive response may lead to dysfunction and eventually failure of the ventricle, which would only be able to eject a significantly smaller amount of blood into circulation. The increase in wall tension has resulted in an increased stretching of the cardiomyocytes as well as non-cardiomyocytes, such as cardiac fibroblasts, which in turn alters both their phenotype and their environment. Research into the mechanobiology of the heart aims to unravel the molecular and cellular mechanisms underlying the physiological response of the heart to load to learn what goes wrong when the heart is faced with sustained pressure overload. This may pave the way to therapeutically interfering with this maladaptive response and thus preventing either the initial hypertrophy or its transition into heart failure. While the heart is mainly subjected to pressure hence stretch as a biomechanical force, the mechanobiology of vascular cells is somewhat more complex. Endothelial cells lining the luminal surface of each blood vessel are continuously subjected to the viscous drag of flowing blood (referred to as fluid shear stress). Fluid shear stress mainly affects the endothelial cells of the small arteries and arterioles, maintaining them in a dormant phenotype. If blood flow is disturbed (e.g. at arterial bifurcations or curvatures) fluid shear stress declines and may give rise to a shift in phenotype of the endothelial cells. A shift from anti-inflammatory to pro-inflammatory in combination with the reduced flow at these sites may enable leukocyte recruitment and diapedesis, which results in a pro-inflammatory response in the vessel wall. Endothelial cells and in particular vascular smooth muscle cells are subjected to another biomechanical force: the blood pressure. Volume-dependent distention of the vessel wall (which can be achieved through an increase in blood flow) results in an increase in wall tension, thereby stretching of the endothelial and smooth muscle cells. Like the cardiomyocytes of the heart, the vascular smooth muscle cells of the small arteries and arterioles try to normalise wall tension by active constriction, which cannot be maintained for long. These cells subsequently undergo hypertrophy or hyperplasia (depending on the size of the blood vessel) and remodel the extracellular matrix so that the vessel wall also becomes thicker and stiffer. This in turn raises their resistance to flow and may contribute to the increase in blood pressure in either the pulmonary or systemic circulation. Research into the mechanobiology of the blood vessels aims to unravel the molecular and cellular mechanisms underlying the physiological response of the vascular cells to pressure (wall tension) and flow (shear stress). It also aims to uncover what goes wrong (e.g. in arteriosclerosis or hypertension) and to eventually specifically interfere with these maladaptive remodelling processes. The aforementioned aspects of cardiovascular mechanobiology along with many more facets of this fascinating, timely and highly clinically relevant field of research are addressed by the original research and review articles within this Research Topic.

This Research Topic is Volume II of a series. The previous volume, which has attracted over 40,000 views can be found here: Bioengineering and Biotechnology Approaches in Cardiovascular Regenerative MedicineCardiovascular diseases continue to be the leading cause of death while available clinical interventions have limited contributions to heart repair and regeneration. Cardiovascular regenerative medicine, characterized by a unique integration of biology, physical sciences, and bioengineering principles, has emerged as one of the most promising fields of translational research to regenerate the adult human heart.

Mechanobiology-the study of the effects of mechanical environments on the biological processes of cells-has evolved from traditional biomechanics via the incorporation of strong elements of molecular and cell biology. Currently, a broad range of organ systems are being studied by surgeons, physicians, basic scientists, and engineers. These mechanob

Mechanobiology—the study of the effects of mechanics on biological events—has evolved to answer numerous research questions. Mechanobiology Handbook 2nd Edition is a reference book for engineers, scientists, and clinicians who are interested in mechanobiology and a textbook for senior undergraduate to graduate level students of this growing field. Readers will gain a comprehensive review of recent research findings as well as elementary chapters on solid mechanics, fluid mechanics, and molecular analysis techniques. The new edition presents, in addition to the chapters of the first edition, homework problem sets that are available online and reviews of research in uncovered areas. Moreover, the new edition includes chapters on statistical analysis, design of experiments and optical imaging. The editors of this book are researchers and educators in mechanobiology. They realized a need for a single volume to assist course instructors as a guide for didactic teaching of mechanobiology to a diverse student body. A mechanobiology course is frequently made up of both undergraduate and graduate students pursuing degrees in engineering, biology, or integrated engineering and biology. Their goal was to present both the elementary and cutting-edge aspects of mechanobiology in a manner that is accessible to students from many different academic levels and from various disciplinary backgrounds. Moreover, it is their hope that the readers of Mechanobiology Handbook 2nd Edition will find study questions at the end of each chapter useful for long-term learning and further discussion. Comprehensive collection of reviews of recent research Introductory materials in mechanics, biology, and statistics Discussion of pioneering and emerging mechanobiology concepts Presentation of cutting-edge mechanobiology research findings across various fields and organ systems End of chapter study questions, available online Considering the complexity of the mechanics and the biology of the human body, most of the world of mechanobiology remains to be studied. Since the field is still developing, the Mechanobiology Handbook raises many different viewpoints and approaches with the intention of stimulating further research endeavours.

This book covers the latest research development in heart valve biomechanics and bioengineering, with an emphasis on novel experimentation, computational simulation, and applications in heart valve bioengineering. The most current research accomplishments are covered in detail, including novel concepts in valvular viscoelasticity, fibril/molecular mechanisms of tissue behavior, fibril kinematics-based constitutive models, mechano-interaction of valvular interstitial and endothelial cells, biomechanical behavior of acellular valves and tissue engineered valves, novel bioreactor designs, biomechanics of transcatheter valves, and 3D heart valve printing. This is an ideal book for biomedical engineers, biomechanics, surgeons, clinicians, business managers in the biomedical industry, graduate and undergraduate students studying biomedical engineering, and medical students.

This Research Topic celebrates the 50th anniversary of the first heart transplant performed in December of 1967 in Cape Town, South Africa. Cardiovascular researchers met in South Africa in December 2017 to commemorate this event, presenting an opportune time to reflect on the achievements of applied cardiovascular research and highlight forthcoming technology developments that will shape the future of cardiovascular medicine. The clinical breakthrough in 1967 offered hope to many patients suffering with cardiac complications, and these life-saving surgeries continue to have a tremendous impact. Tissue shortages, surgical risks, and complications due to improper host-transplant tissue interactions, however, limit the utility of heart transplants to the most severe cases of cardiac morbidity. Recent advances have yielded mechanistic insight into the factors that control cardiovascular tissue maintenance and remodeling. The field of regenerative medicine seeks to control these factors to promote in situ tissue regeneration or engineered tissue replacement. These exciting new technologies could lead to a renaissance in the treatment of many cardiovascular diseases, just as the realization of heart transplantation 50 years ago. In this Research Topic, researchers and clinicians from regenerative medicine and applied cardiovascular biology provide literature reviews and original manuscripts to demonstrate the trajectory of cardiovascular medicine. The contributions vertically integrate advances by clinicians, engineers, and basic scientists, all researching similar topics from different angles and with complementary perspectives. Taken together, these contributions demonstrate the process of applied cardiovascular research from basic science discoveries to implementation in clinical practice.