An emerging field at the interface of biology and engineering, mechanobiology explores the mechanisms by which cells sense and respond to mechanical signals—and holds great promise in one day unravelling the mysteries of cellular and extracellular matrix mechanics to cure a broad range of diseases. Mechanobiology: Exploitation for Medical Benefit presents a comprehensive overview of principles of mechanobiology, highlighting the extent to which biological tissues are exposed to the mechanical environment, demonstrating the importance of the mechanical environment in living systems, and critically reviewing the latest experimental procedures in this emerging field. Featuring contributions from several top experts in the field, chapters begin with an introduction to fundamental mechanobiological principles; and then proceed to explore the relationship of this extensive force in nature to tissues of musculoskeletal systems, heart and lung vasculature, the kidney glomerulus, and cutaneous tissues. Examples of some current experimental models are presented conveying relevant aspects of mechanobiology, highlighting emerging trends and promising avenues of research in the development of innovative therapies. Timely and important, Mechanobiology: Exploitation for Medical Benefit offers illuminating insights into an emerging field that has the potential to revolutionise our comprehension of appropriate cell biology and the future of biomedical research.

Table of Contents:
  List of Contributors xiii Preface xvii 1 Extracellular Matrix Structure and Stem Cell Mechanosensing 1 Nicholas D. Evans and Camelia G. Tusan 1.1 Mechanobiology 1 1.2 Stem Cells 3 1.3 Substrate Stiffness in Cell Behavior 5 1.3.1 A Historical Perspective on Stiffness Sensing 5 1.4 Stem Cells and Substrate Stiffness 7 1.4.1 ESCs and Substrate Stiffness 8 1.4.2 Collective Cell Behavior in Substrate Stiffness Sensing 11 1.5 Material Structure and Future Perspectives in Stem Cell Mechanobiology 14 1.6 Conclusion 15 References 16 2 Molecular Pathways of Mechanotransduction: From Extracellular Matrix to Nucleus 23 Hamish T. J. Gilbert and Joe Swift 2.1 Introduction: Mechanically Influenced Cellular Behavior 23 2.2 Mechanosensitive Molecular Mechanisms 24 2.3 Methods Enabling the Study of Mechanobiology 29 2.4 Conclusion 34 Acknowledgements 34 References 34 3 Sugar-Coating the Cell: The Role of the Glycocalyx in Mechanobiology 43 Stefania Marcotti and Gwendolen C. Reilly 3.1 What is the Glycocalyx? 43 3.2 Composition of the Glycocalyx 44 3.3 Morphology of the Glycocalyx 45 3.4 Mechanical Properties of the Glycocalyx 46 3.5 Mechanobiology of the Endothelial Glycocalyx 49 3.6 Does the Glycocalyx Play a Mechanobiological Role in Bone? 50 3.7 Glycocalyx in Muscle 52 3.8 How Can the Glycocalyx be Exploited for Medical Benefit? 53 3.9 Conclusion 53 References 54 4 The Role of the Primary Cilium in Cellular Mechanotransduction: An Emerging Therapeutic Target 61 Kian F. Eichholz and David A. Hoey 4.1 Introduction 61 4.2 The Primary Cilium 63 4.3 Cilia-Targeted Therapeutic Strategies 68 4.4 Conclusion 70 Acknowledgements 70 References 70 5 Mechanosensory and Chemosensory Primary Cilia in Ciliopathy and Ciliotherapy 75 Surya M. Nauli, Rinzhin T. Sherpa, Caretta J. Reese, and Andromeda M. Nauli 5.1 Introduction 75 5.2 Mechanobiology and Diseases 76 5.3 Primary Cilia as Biomechanics 78 5.4 Modulating Mechanobiology Pathways 83 5.5 Conclusion 85 References 86 6 Mechanobiology of Embryonic Skeletal Development: Lessons for Osteoarthritis 101 Andrea S. Pollard and Andrew A. Pitsillides 6.1 Introduction 101 6.2 An Overview of Embryonic Skeletal Development 102 6.3 Regulation of Joint Formation 103 6.4 Regulation of Endochondral Ossification 105 6.5 An Overview of Relevant Osteoarthritic Joint Changes 106 6.6 Lessons for Osteoarthritis from Joint Formation 108 6.7 Lessons for Osteoarthritis from Endochondral Ossification 109 6.8 Conclusion 110 Acknowledgements 111 References 111 7 Modulating Skeletal Responses to Mechanical Loading by Targeting Estrogen Receptor Signaling 115 Gabriel L. Galea and Lee B. Meakin 7.1 Introduction 115 7.2 Biomechanical Activation of Estrogen Receptor Signaling: In Vitro Studies 116 7.3 Skeletal Consequences of Altered Estrogen Receptor Signaling: In Vivo Mouse Studies 120 7.4 Skeletal Consequences of Human Estrogen Receptor Polymorphisms: Human Genetic and Exercise-Intervention Studies 125 7.5 Conclusion 126 References 126 8 Mechanical Responsiveness of Distinct Skeletal Elements: Possible Exploitation of Low Weight-Bearing Bone 131 Simon C. F. Rawlinson 8.1 Introduction 131 8.2 Anatomy and Loading-Related Stimuli 132 8.3 Preosteogenic Responses In Vitro 135 8.4 Site-Specific, Animal-Strain Differences 136 8.5 Exploitation of Regional Information 137 8.6 Conclusion 138 References 138 9 Pulmonary Vascular Mechanics in Pulmonary Hypertension 143 Zhijie Wang, Lian Tian, and Naomi C. Chesler 9.1 Introduction 143 9.2 Pulmonary Vascular Mechanics 143 9.3 Measurements of Pulmonary Arterial Mechanics 147 9.4 Mechanobiology in Pulmonary Hypertension 150 9.5 Computational Modeling in Pulmonary Circulation 151 9.6 Impact of Pulmonary Arterial Biomechanics on the Right Heart 152 9.7 Conclusion 153 References 153 10 Mechanobiology and the Kidney Glomerulus 161 Franziska Lausecker, Christoph Ballestrem, and Rachel Lennon 10.1 Introduction 161 10.2 Glomerular Filtration Barrier 161 10.3 Podocyte Adhesion 163 10.4 Glomerular Disease 165 10.5 Forces in the Glomerulus 166 10.6 Mechanosensitive Components and Prospects for Therapy 167 10.7 Conclusion 169 References 169 11 Dynamic Remodeling of the Heart and Blood Vessels: Implications of Health and Disease 175 Ken Takahashi, Hulin Piao, and Keiji Naruse 11.1 Introduction 175 11.2 Causes of Remodeling 176 11.3 Mechanical Transduction in Cardiac Remodeling 177 11.4 The Remodeling Process 178 11.5 Conclusion 183 References 183 12 Aortic Valve Mechanobiology: From Organ to Cells 191 K. Jane Grande-Allen, Daniel Puperi, Prashanth Ravishankar, and Kartik Balachandran 12.1 Introduction 191 12.2 Mechanobiology at the Organ Level 192 12.3 Mechanobiology at the Cellular Level 197 12.4 Conclusion 201 Acknowledgments 201 References 201 13 Testing the Perimenopause Ageprint using Skin Visoelasticity under Progressive Suction 207 Gérald E. Piérard, Claudine Piérard-Franchimont, Ulysse Gaspard, Philippe Humbert, and Sébastien L. Piérard 13.1 Introduction 207 13.2 Gender-Linked Skin Aging 208 13.3 Dermal Aging, Thinning, and Wrinkling 209 13.4 Skin Viscoelasticity under Progressive Suction 209 13.5 Skin Tensile Strength during the Perimenopause 211 13.6 Conclusion 214 Acknowledgements 215 References 216 14 Mechanobiology and Mechanotherapy for Skin Disorders 221 Chao-Kai Hsu and Rei Ogawa 14.1 Introduction 221 14.2 Skin Disorders Associated with Mechanobiological Dysfunction 223 14.3 Mechanotherapy 231 14.4 Conclusion 232 Acknowledgement 232 References 233 15 Mechanobiology and Mechanotherapy for Cutaneous Wound-Healing 239 Chenyu Huang, Yanan Du, and Rei Ogawa 15.1 Introduction 239 15.2 The Mechanobiology of Cutaneous Wound-Healing 240 15.3 Mechanotherapy to Improve Cutaneous Wound-Healing 242 15.4 Future Considerations 246 References 246 16 Mechanobiology and Mechanotherapy for Cutaneous Scarring 255 Rei Ogawa and Chenyu Huang 16.1 Introduction 255 16.2 Cutaneous Wound-Healing and Mechanobiology 255 16.3 Cutaneous Scarring and Mechanobiology 256 16.4 Cellular and Tissue Responses to Mechanical Forces 257 16.5 Keloids and Hypertrophic Scars and Mechanobiology 258 16.6 Relationship Between Scar Growth and Tension 260 16.7 A Hypertrophic Scar Animal Model Based on Mechanotransduction 261 16.8 Mechanotherapy for Scar Prevention and Treatment 262 16.9 Conclusion 263 References 264 17 Mechanobiology and Mechanotherapy for the Nail 267 Hitomi Sano and Rei Ogawa 17.1 Introduction 267 17.2 Nail Anatomy 267 17.3 Role of Mechanobiology in Nail Morphology 268 17.4 Nail Diseases and Mechanical Forces 269 17.5 Current Nail Treatment Strategies 270 17.6 Mechanotherapy for Nail Deformities 270 17.7 Conclusion 271 References 271 18 Bioreactors: Recreating the Biomechanical Environment In Vitro 275 James R. Henstock and Alicia J. El Haj 18.1 The Mechanical Environment: Forces in the Body 275 18.2 Bioreactors: A Short History 276 18.3 Bioreactor Types 278 18.4 Commercial versus Homemade Bioreactors 288 18.5 Automated Cell-Culture Systems 289 18.6 The Future of Bioreactors in Research and Translational Medicine 290 References 291 19 Cell Sensing of the Physical Properties of the Microenvironment at Multiple Scales 297 Julien E. Gautrot 19.1 Introduction 297 19.2 Cells Sense their Mechanical Microenvironment at the Nanoscale Level 298 19.3 Cell Sensing of the Nanoscale Physicochemical Landscape of the Environment 306 19.4 Cell Sensing of the Microscale Geometry and Topography of the Environment 312 19.5 Conclusion 319 References 319 20 Predictive Modeling in Musculoskeletal Mechanobiology 331 Hanifeh Khayyeri, Hanna Isaksson, and Patrick J. Prendergast 20.1 What is Mechanobiology? Background and Concepts 331 20.2 Examples of Mechanobiological Experiments 333 20.3 Modeling Mechanobiological Tissue Regeneration 337 20.4 Mechanoregulation Theories for Bone Regeneration 338 20.5 Use of Computational Modeling Techniques to Corroborate Theories and Predict Experimental Outcomes 340 20.6 Horizons of Computational Mechanobiology 341 References 343 21 Porous Bone Graft Substitutes: When Less is More 347 Charlie Campion and Karin A. Hing 21.1 Introduction 347 21.2 Bone: The Ultimate Smart Material 350 21.3 Bone-Grafting Classifications 353 21.4 Synthetic Bone Graft Structures 356 21.5 Conclusion 361 References 362 22 Exploitation of Mechanobiology for Cardiovascular Therapy 373 Winston Elliott, Amir Keshmiri, and Wei Tan 22.1 Introduction 373 22.2 Arterial Wall Mechanics and Mechanobiology 374 22.3 Mechanical Signal and Mechanotransduction on the Arterial Wall 375 22.4 Physiological and Pathological Responses to Mechanical Signals 377 22.5 The Role of Vascular Mechanics in Modulating Mechanical Signals 378 22.6 Therapeutic Strategies Exploiting Mechanobiology 380 22.7 The Role of Hemodynamics in Mechanobiology 381 22.8 Conclusion 390 References 391 Index 401