A Tissue Regeneration Approach to Bone and Cartilage Repair (eBook)

Hala Zreiqat is expert in developing biomaterials for bone/cartilage tissue repair and regeneration and the in vivo/in vitro assessment of cell-biomaterial interaction. Colin Dunstan is an expert in bone cell biology and the interrelationships between bone cells and their microenvironment. Vicki Rosen is an expert is studying the physiological roles that bone morphogenetic proteins (BMPs) play in the development, maintenance, and repair of musculoskeletal tissues (bone, cartilage, tendon, ligament, meniscus, muscle).

Contents 6
Ligand–Receptor Interactions and Their Implications in Delivering Certain Signaling for Bone Regeneration 8
Abstract 8
1 Introduction 8
2 The Identification of BMPs as Members of the TGF-? Family 9
3 Experimental Models for Evaluating Bone Formation 10
4 Regulation of Ligand Modifications 11
5 Regulation of Receptor Activation 12
6 Regulation by Antagonists 13
7 Regulation of Intracellular Signaling Effectors 15
8 Cross-Talk with Other Signaling Molecules 17
9 Conclusions 19
References 19
BMPs and Wnts in Bone and Cartilage Regeneration 23
Abstract 23
1 BMP Signaling in Bone and Cartilage Regeneration 23
1.1 Bmp-2 24
1.2 Bmp-4 26
1.2.1 Cartilage Repair 26
1.2.2 Bone-Tendon-Muscle Interaction 26
1.3 Bmp-6 27
1.3.1 Cartilage Repair 27
1.3.2 Bone Regeneration 28
1.4 Bmp-7 28
1.4.1 Cartilage Repair and Arthritis 28
1.4.2 Meniscus Repair 29
1.4.3 Fracture and Spinal Fusion 29
1.5 Bmp-9 30
1.6 Cross-Talk Between BMP and Wnt Signaling 30
2 Wnt?-Catenin Signaling in Bone and Cartilage Regeneration 31
2.1 Scl-Ab 32
2.1.1 Scl-Ab in Ovariectomy-Induced Bone Loss 32
2.1.2 Scl-Ab in Bone Mechanical Strength 32
2.1.3 Scl-Ab in Bone Fracture Healing 33
2.1.4 Scl-Ab in Osteogenesis Imperfecta 33
2.1.5 Potential Side Effect 34
2.2 Dkk1-Ab 35
References 36
Osteocytes and Bone Regeneration 44
Abstract 44
1 Introduction 44
2 Bone Matrix Repair by Osteocytes 45
2.1 Osteocyte Apoptosis and Bone Matrix Microdamage 46
2.2 Mechanisms of Osteocyte Mediated Matrix Repair 47
2.2.1 RANKL Mediated Osteoclastogenesis 47
2.2.2 Osteocyte Induction of Angiogenesis 47
2.2.3 Osteocytic Osteolysis 48
2.2.4 Osteocyte Control of Bone Matrix Mineralisation 49
3 Osteocytes in Fracture 50
4 Osteocytes as Regulators of Bone Formation 51
5 Summary 53
References 53
Skeletal Stem Cells for Bone and Cartilage Tissue Regeneration 58
Abstract 58
1 Bone Marrow Microenvironment and Bone Marrow Stem Cells 59
2 MSCs: Road to Clinical Use 60
2.1 MSC Homing to Injured Tissues 60
3 Specific Uses of BMSCs in Skeletal Regeneration 62
3.1 Fractures and Bone Defects 62
3.2 Osteoporosis 63
3.3 Cartilage Repair and Rheumatic Diseases 63
4 Concluding Remarks 64
References 65
Manipulation of Macrophages to Enhance Bone Repair and Regeneration 69
Abstract 69
1 Introduction 69
2 Role of Inflammation in Bone Healing 70
3 Impact of Chronic Inflammation on Bone Healing 72
4 Macrophage Polarization as a Potential Therapeutic Strategy 74
5 Strategies to Actively Manipulate Macrophage Behavior 76
5.1 Cell Delivery 77
5.2 Drug and Protein Delivery 78
5.3 Physical Modification of Scaffold Properties 79
5.4 Selectively Delivery to Macrophages Using Nanoparticles 80
6 Conclusions 81
References 82
Cartilage Regeneration Using Induced Pluripotent Stem Cell Technologies 89
Abstract 89
1 The Structure and Limited Repair Capacity of Cartilage 89
2 Cell Transplantation into Articular Cartilage Defects 91
3 The Use of iPSC-Derived Chondrocytes 92
3.1 Generation of iPSCs 92
3.2 Improvement of the Safety of iPSCs 94
3.3 Transplantation of iPSC-Derived Chondrocytes into Articular Cartilage Defects of Patients 94
3.4 Development of an iPSC Library 96
4 Use of Chondrogenic Cells Generated by Direct Conversion 96
4.1 Cell-Type Conversion Without the Need for iPS Cells 96
4.2 Direct Conversion of Dermal Fibroblasts into Chondrogenic Cells 97
5 Conclusions 98
References 99
Alveolar Augmentation: Focus on Growth Factors (BMPs) 103
Abstract 103
1 Introduction 104
2 Alveolar Augmentation 106
3 Clinical Modeling 109
4 Alternative Carrier Technologies 110
5 rhBMP-2 Coated Dental Implants 112
6 Alveolar Augmentation in Clinical Settings 114
References 118
Bone-Biomimetic Biomaterial and Cell Fate Determination 123
Abstract 123
1 Introduction 124
2 Biomaterial Design for Bone Regeneration 125
2.1 Designs to Mimic Physical Characteristics of Bone 125
2.1.1 Designs to Mimic Architecture of Bone 125
2.1.2 Designs to Mimic Topography of Bone 126
2.1.3 Designs to Mimic Mechanical Properties of Bone 127
2.2 Designs to Mimic Chemical Composition of Bone 129
2.2.1 Designs to Mimic Organic Phase of Bone 129
2.2.2 Designs to Mimic Mineral Phase of Bone 131
3 Mechanisms of Cell Fate Determination by Bone-Biomimetic Biomaterial 132
3.1 Protein Adsorption 133
3.2 Integrin Signalling 134
3.2.1 Integrin Downstream Signalling Pathways 136
ERKMAPK Signalling Pathway 136
RhoROCK Signalling Pathway 137
PI3K-Akt Signalling Pathway 138
3.2.2 Crosstalk Between Integrin and Growth Factor Signalling 139
4 Summary, Conclusion and Perspectives 139
References 140
Biomimetic Scaffolds for Craniofacial Bone Tissue Engineering: Understanding the Role of the Periosteum in Regeneration 151
Abstract 151
1 Introduction 152
2 The Role of the Periosteum in Bone Development and Regeneration 154
2.1 Periosteal Involvement in Wound Healing Initiation 154
2.2 BMP Signaling 154
2.3 Hedgehog Signaling 155
2.4 Wnt Signaling 156
2.5 Periosteal Cell Recruitment and Function 156
2.6 Vascularization and Extracellular Environment 156
3 Tissue Engineered Electrospun Hydroxyapatite Containing Chitosan Scaffolds 157
3.1 Key Features of Tissue Engineered Bone Scaffolds 157
3.2 Electrospinning and Scaffold Fabrication 158
3.3 HA Containing Chitosan Scaffolds are Osteoinductive 160
3.4 HA Containing Chitosan Scaffolds are OsseointegrativeOsteoconductive 161
3.5 Conclusions 164
References 165
Biomaterials Used for Maxillofacial Regeneration 170
Abstract 170
1 Introduction 170
2 Current Clinical Treatments for Maxillofacial Bone Regeneration 171
2.1 Bone Grafting 171
2.1.1 Autografts 171
2.1.2 Allografts 172
2.1.3 Xenografts 173
2.2 Distraction Osteogenesis 173
2.3 Guided Bone Regeneration 174
3 The Biomaterials Used for Maxillofacial Bone Regeneration 174
3.1 Biomaterials Clinically Used for Maxillofacial Regeneration 174
3.2 Recent Advances in Biomaterials Used for Maxillofacial Regeneration 176
3.2.1 Structural Design 177
Nanotechnology 177
CADCAM Technique 180
3.2.2 Bioinorganics 182
Magnesium 182
Strontium 182
Zinc 183
Copper 184
Lithium 184
3.2.3 Angiogenesis 185
4 Summary and Future Directions 186
References 187
Advances and Applications of Nanomechanical Tools in Cartilage Tissue Engineering 194
Abstract 194
1 Introduction 195
2 Heterogeneity of Native Cartilage at a Hierarchy of Length Scales 197
3 Current Advances in Nanomechanical Methods 199
3.1 AFM-Based Nanoindentation 199
3.2 AFM-Based Force Spectroscopy and Imaging 202
3.3 Other Nanomechanical Techniques 203
3.4 Multiscale Modeling 203
4 Applications of Nanomechanics to Cartilage Tissue Engineering 204
4.1 Effects of Cytokines on Chondrocyte Synthesis 204
4.2 Effects of Mechanical Loading on Chondrocyte Synthesis 206
4.3 Engineered Aggrecan by Bone Marrow Stromal Cells 207
4.4 Engineered Tissue by Induced Pluripotent Stem Cells 210
4.5 Chondrogenesis Differentiation of Adipose-Derived Stem Cells 211
5 Summary and Future Outlook 212
References 213
Signalling Pathways in Osteochondral Defect Regeneration 222
Abstract 222
1 Introduction 222
2 Definition of the Osteochondral Unit and Osteochondral Defects 223
3 Principles of Tissue Regeneration in Osteochondral Defects 225
3.1 Cartilage Regeneration in Osteochondral Defects 225
3.2 Bone Regeneration in Osteochondral Defects 227
3.3 Interplay Between Cartilage and Bone Regeneration in Osteochondral Defects 227
4 Conclusions 228
References 229
Polymer-Assisted Cartilage and Tendon Repair 232
Abstract 232
Abbreviation List 233
1 Introduction 233
1.1 Unmet Medical Need 234
2 Articular Cartilage 235
3 Healing in Cartilage 236
4 Tendons and Healing Tendon 237
5 Reconstruction of Articular Cartilage and Tendon-to-Bone Interface 239
5.1 Articular Cartilage-to-Bone Interface 239
5.1.1 Fibrocartilaginous Enthesis 239
6 Cell Sources and Properties 240
7 Expansion of Chondrocytes and Tenocytes for TE 241
8 Polymers for Cartilage and Tendon TE 242
8.1 Natural Polymers 242
8.1.1 Collagen 242
8.1.2 Silk and Chitosan 243
8.1.3 Decellularized Extracellular Matrices 243
9 Synthetic Polymers 244
10 Polymer-Based Hydrogels for TE 245
10.1 Cartilage 245
10.2 Tendon 245
11 HybridBiphasic Scaffolds 246
11.1 Cartilage 246
11.2 Tendon 246
12 Tools to Optimize Culture Conditions for Cartilage and Tendon TE 246
12.1 Cell Numbers 246
12.2 Seeding Conditions 247
12.3 Growth Factors in TE 247
12.3.1 Growth Factors for Tendon TE 247
12.3.2 Growth Factors for Cartilage TE 248
13 Polymer Topology 248
14 Conclusion: Future Challenges 249
References 250