Title Details

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