Biomaterials for Cardiac Regeneration (eBook)

Preface 8
Acknowledgements 10
Contents 12
Chapter 1: The Role of Extracellular Matrix in Cardiac Development 17
1.1 Introduction 18
1.1.1 Overview of Heart Development 19
1.1.2 Overview of the Extracellular Matrix 19
1.2 Major Components of and Contributors to the Cardiac ECM 21
1.2.1 Integrins and Other ECM Receptors 21
1.2.2 Collagens 23
1.2.3 Glycoproteins 24
1.2.4 Glycosaminoglycans and Proteoglycans 25
1.2.5 Other Proteins 26
1.2.6 Growth Factors and Other Signaling Molecules 27
1.2.7 Matrix Metalloproteinases and Their Inhibitors 27
1.2.8 Cardiac Fibroblasts 28
1.3 The Cardiac ECM During Prenatal Development 28
1.3.1 The Cardiac Crescent 30
1.3.2 The Heart Tube 30
1.3.3 Heart Looping 31
1.3.4 Endocardial Cushions and Valve Development 31
1.3.5 Growth and Maturation of the Developing Heart 32
1.4 The ECM in the Perinatal and Mature Heart 34
1.5 The Role of ECM in Cardiovascular Disorders 35
1.5.1 Pediatric CHDs and CVDs 36
1.5.2 Adult CVDs 37
1.6 Regenerative Vertebrates 38
1.7 ECM as a Biomaterial for Cardiac Regeneration 38
1.8 Summary and Perspective 40
References 41
Chapter 2: Role of Embryonic and Differentiated Cells in Cardiac Development 52
2.1 Introduction 53
2.2 Contribution of Various Lineages to Heart Development 53
2.3 Myocardial Cell Lineage 55
2.4 The Secondary Heart Field 58
2.5 Regulation of Endocardial Cell Proliferation and Differentiation 60
2.6 Epicardial Derived Cardiac Cells 63
2.7 Differentiation of Cardiac Conduction Cells 66
2.8 Neural Crest Contribution to the Heart 69
2.9 Induction of Cardiac Cell Fates in Differentiated Cells and Stem Cells 71
2.10 Challenges and Future Directions for Heart Repair 73
References 74
Chapter 3: Spatial and Electrical Factors Regulating Cardiac Regeneration and Assembly 86
3.1 Introduction 87
3.2 Cell Source and Maturity: The Need for Guidance 87
3.3 Scaffold Directed Self-Assembly 90
3.3.1 Hydrogels 90
3.3.2 Anisotropic Guidance 92
3.3.2.1 Patterned Surfaces 92
3.3.2.2 Topography 94
3.3.2.3 3D Scaffolds 96
Nanofibrous Scaffolds 96
Cellular Frameworks 96
3.3.3 Electrically Conductive Scaffolds 97
3.4 Stretch Induced Assembly 99
3.4.1 Static Stretch 99
3.4.2 Cyclic Stretch 100
3.5 Electrically Directed Assembly 101
3.6 Conclusions 102
3.7 Future Perspectives 103
References 103
Chapter 4: Microenvironmental Control of Stem Cell Fate 108
4.1 Introduction 108
4.2 Control of Cell Fate by ECM Mechanics 112
4.3 Control of Cell Fate by ECM Topography 115
4.4 Control of Cell Fate by Proximity to the Microvasculature 118
4.5 Microenvironmental Control of Reprogramming 121
4.6 Implications for the Design of Biomaterials for Cardiac Regenerative Medicine 124
References 124
Chapter 5: Matrix Therapies for Cell Support and Cardiac Repair 131
5.1 Introduction 131
5.2 Cardiac Cells and the Myocardial Extracellular Matrix 132
5.2.1 Cardiac Repair: Alternatives and Approaches 141
5.2.2 Cell-Based Regenerative Therapy 142
5.2.3 Biomaterial Strategies 143
5.3 Biomaterials and Their Applications 143
5.3.1 Collagen 143
5.3.1.1 Interaction Between Cells and Collagen 143
5.3.1.2 Function of Collagen in Cardiac Repair 145
5.3.1.3 Collagen-Based Biomaterials 146
5.3.2 Alginate 148
5.3.3 Fibrin 151
5.3.4 Matrigel 151
5.3.5 Cardiogel 153
5.3.6 Hyaluronic Acid 153
5.3.7 Decellularized Extracellular Matrix 154
5.3.8 Chitosan 156
5.3.9 Self-Assembling Peptides 157
5.3.10 Synthetic Polymers 158
5.4 Conclusions 159
5.5 Future Perspectives 160
References 160
Chapter 6: Growth Factor Delivery Matrices for Cardiovascular Regeneration 173
6.1 Introduction 174
6.1.1 CV Anatomy 174
6.1.2 Changes to Cardiac and Aortic Wall Tissues in Injury and Disease 176
6.2 GFs in Vascular Regeneration 179
6.2.1 GFs in CV Tissue Regeneration 180
6.2.2 Need for GF Delivery Vehicles 187
6.3 Biomaterial-Based Strategies for GF Delivery 188
6.3.1 Strategies for GF delivery 195
6.3.1.1 Chemical Immobilization of GFs 195
6.3.1.2 Physical Encapsulation of GFs 197
6.4 Strategies for Dual Growth Factor Delivery 201
6.5 Enabling GF Delivery on Demand 202
6.5.1 Temperature and/or pH Sensitive GF Release 204
6.5.2 Protease-Triggered GF Release 206
6.5.3 Controlled GF Release with Drugs, Ions, Light, External Magnetic and Electric Fields 207
6.6 Scaffolds for Standalone Cell Delivery and for Co-delivery with GFs 208
6.7 Conclusions and Perspectives on Future Directions 211
References 211
Chapter 7: Whole-Heart Tissue Engineering: Use of Three-Dimensional Matrix Scaffolds 229
7.1 End-Stage Heart Failure: Clinical Background 229
7.2 The Heart in the Context of Whole-Organ Tissue Engineering 231
7.2.1 Whole-Organ Tissue Engineering 231
7.2.2 Whole-Heart Tissue Engineering 233
7.3 Whole-Heart Decellularization 234
7.4 Recellularization of Decellularized Whole-Heart Scaffolds 237
7.4.1 Cell Source 238
7.4.2 Cell Seeding 240
7.5 In Vitro Conditioning and Maturation of Recellularized Whole-Heart Scaffolds 242
7.6 Clinical Perspective 244
References 245
Chapter 8: Immunological and Phenotypic Considerations in Supplementing Cardiac Biomaterials with Cells 252
8.1 Introduction 253
8.2 Tissue and Organ Rejection in the Cardiovascular System 253
8.2.1 Heart Transplantation 253
8.2.2 Allograft Valve Rejection 256
8.2.3 Xenogeneic Valve Rejection 257
8.3 Biomaterial Implants 259
8.3.1 The Foreign Body Response to Biomaterials 259
8.3.2 Considerations for Biomaterial-Based Cardiovascular Devices 261
8.3.2.1 Stents and Vascular Grafts 262
8.3.2.2 Artificial Heart Valves 264
Valvular Composition 264
Current Valve Replacement Options 265
Concerns Related to Calcification 266
Concerns with Immunogenicity 267
Tissue Engineered Heart Valves 267
Autologous Versus Heterologous Pericardial Valves 272
8.3.2.3 Patches 272
8.4 Stem Cell Therapies 273
8.4.1 Stem Cells for Cardiac Regeneration 273
8.4.2 Immunomodulatory Effects of Stem Cells 275
8.4.3 Stem Cells and Cancer 276
8.5 Conclusions and Future Directions 277
References 278
Chapter 9: Imaging of the Biomaterial Structure and Function 287
9.1 Introduction 288
9.2 Optical Imaging 290
9.2.1 Light Microscopy 290
9.2.2 Scanning Electron Microscopy 291
9.2.3 Optical Coherence Tomography 291
9.2.4 Fluorescence Microscopy 293
9.2.5 Bioluminescence Imaging 293
9.3 Ultrasound Imaging 294
9.4 Photoacoustic Microscopy 296
9.5 Magnetic Resonance Imaging 296
9.6 X-ray Computed Tomography 297
9.7 Nuclear Imaging 297
9.8 Multimodal Molecular Imaging Techniques 300
9.9 Conclusions 301
References 301
Chapter 10: Autologous Bioengineered Heart Valves: An Update 306
10.1 Introduction 307
10.2 Structure of Cardiac Valves 307
10.3 Scaffolds 308
10.3.1 Polymer Scaffolds 308
10.3.2 Decellularized Scaffolds 310
10.4 Cell Sources 311
10.5 Bioreactors 312
10.6 Clinical Applications 313
10.7 Future Directions 315
References 315
Chapter 11: Safety, Regulatory, and Ethical Issues of Human Studies 319
11.1 Introduction 319
11.2 Safety Issues 320
11.2.1 Arrhythmias 320
11.2.2 Tumor Development 321
11.2.3 Rejection 323
11.2.4 Stent Restenosis/Thrombosis 323
11.2.5 Calcification 324
11.3 Regulatory Issues 324
11.3.1 Preclinical Studies 324
11.3.2 Cell Manufacturing 325
11.3.3 Release Criteria 327
11.3.4 Cell and Scaffold Combined Products 328
11.4 Ethical Issues 330
11.5 Conclusion 332
References 332