Regenerative Strategies for the Treatment of Knee Joint Disabilities (eBook)

Preface 6
Contents 7
Articular Cartilage Lesions: Clinical Management and Regenerative Strategies 10
1 Knee Articular Cartilage 11
Abstract 11
1.1 Introduction and Types of Cartilage in the Human Body 11
1.2 Anatomy of the Knee Joint 12
1.3 Gross Anatomy and Function of Articular Cartilage 13
1.4 Embriology of Articular Cartilage 13
1.5 Structure and Biochemistry of Articular Cartilage 14
1.5.1 Chondrocytes 14
1.5.2 Constituents of Extracellular Matrix (ECM) 16
1.5.2.1 Proteoglycans and Gylcosaminoglycans 17
1.5.2.2 Collagens 18
1.5.2.3 Non-Collagenous Proteins of AC 19
1.5.3 Synovial Fluid 19
1.6 Ultrastructure of Articular Cartilage 20
1.6.1 Subchondral Bone 21
1.7 Cartilage Homeostasis 21
1.7.1 Biomechanical Loading 21
1.7.2 Mechanical Behaviour of Articular Cartilage 22
1.7.3 Anabolic and Catabolic Factors 23
1.8 Final Remarks 25
References 25
2 Synovial Knee Joint 29
Abstract 29
2.1 Introduction 29
2.2 Synovial Membrane 32
2.3 Synovitis 32
2.4 Final Remarks 35
References 35
3 Clinical Management of Articular Cartilage Lesions 37
Abstract 37
3.1 Introduction 38
3.2 Clinical Findings 38
3.3 Treatment 45
3.3.1 Paliative Treatments 45
3.3.2 Reparative Treatments 46
3.3.3 Regenerative Treatments 50
References 55
4 Osteoarthritis 62
Abstract 62
4.1 Introduction 62
4.2 Epidemiology and Socioeconomic Impact 64
4.3 Pathobiology of OA 65
4.3.1 Early Changes 65
4.3.1.1 Chondrocyte Hypertrophy 65
4.3.1.2 Changes in Cartilage ECM Synthesis 65
4.3.1.3 Early Morphological Alterations 67
4.4 Advanced Stage of OA 67
4.4.1 Chondrocyte Apoptosis 67
4.4.2 Morphological Changes 68
4.4.3 Molecular Alterations During the Later Stages of OA 69
4.4.4 Inflammation in OA 70
4.5 Final Remarks 71
References 72
5 Cartilage Tissue Engineering and Regenerative Strategies 80
Abstract 80
5.1 Introduction 80
5.2 Articular Cartilage 81
5.3 Tissue Engineering and Regenerative Strategies 82
5.3.1 Material 82
5.3.1.1 Cell Sources 82
Chondrocytes 82
Stem Cells 84
5.3.1.2 Scaffolds 86
5.3.1.3 Growth Factors 87
5.3.2 Strategies 88
5.3.2.1 Current Repair Techniques 89
5.3.2.2 Scaffold-Based Strategies 90
5.3.2.3 Scaffold-Free Approaches 91
5.3.2.4 3D Bioprinting 92
5.3.2.5 Gene Therapy 92
References 93
6 Advances in Biomaterials for the Treatment of Articular Cartilage Defects 104
Abstract 104
6.1 Introduction 104
6.2 Biomaterials Used for Cartilage Tissue Engineering 106
6.2.1 Natural Polymers 107
6.2.1.1 Proteins 107
Collagen 107
Silk Fibroin 109
6.2.1.2 Polysaccharides 110
Alginate 110
Chitosan 112
Hyaluronic Acid 113
Gellan Gum 115
Chondroitin Sulphate 116
Cellulose 117
Agarose 118
6.2.2 Synthetic Polymers 119
6.2.2.1 Poly(ethylene glycol) 119
6.2.2.2 Poly(lactic-co-glycolic acid) 120
6.2.2.3 Poly-L-Lactic Acid 121
6.2.2.4 Polycaprolactone 121
6.2.2.5 Poly(N-Isopropylacrylamide) 122
6.2.3 Others 123
6.3 Final Remarks 124
References 124
Osteochondral Lesions of the Knee: From Repair towards Regeneration 134
7 Fundamentals on Osteochondral Tissue Engineering 135
Abstract 135
7.1 Introduction 135
7.2 Osteochondral Tissue: Structure and Properties 137
7.2.1 Articular Cartilage 137
7.2.2 Subchondral Bone 139
7.3 Strategies for Osteochondral Tissue Engineering 141
7.3.1 Bilayered Scaffolds 141
7.3.2 Fibrous Scaffolds 144
7.3.3 Hydrogel Scaffolds 146
7.4 Concluding Remarks 148
Acknowledgments 148
References 148
8 Pre-clinical and Clinical Management of Osteochondral Lesions 153
Abstract 153
8.1 Introduction 154
8.2 Pre-clinical Studies for Osteochondral Regeneration 156
8.3 Clinical Trials for Osteochondral Regeneration 159
8.4 Marketed Products for Osteochondral Regeneration 161
8.5 Conclusions 162
Acknowledgments 163
References 163
9 Rapid Prototyping for the Engineering of Osteochondral Tissues 168
Abstract 168
9.1 Introduction 168
9.2 Rapid Prototyping Technology for Osteochondral Tissue Engineering Applications 170
9.2.1 Laser-Based Techniques 171
9.2.2 Nozzled-Based Techniques 175
9.2.3 Printer-Based Techniques 179
9.3 Bioprinting 181
9.4 Conclusions 183
References 184
10 Biomimetic Approaches for the Engineering of Osteochondral Tissues 191
Abstract 191
10.1 Introduction 192
10.2 Non-layered Scaffolds for Engineering OC Tissue 193
10.2.1 Influences of Material’s Intrinsic Property and Scaffold’s Structure 193
10.2.2 Bioactive Factors 194
10.3 Biomimetic Approaches for Engineering of OC Tissue 195
10.3.1 Layered Scaffolds for Engineering of OC Tissue 196
10.3.1.1 Bilayered Scaffolds with Component Dependence 196
10.3.1.2 Bilayered Scaffolds with Cell Source Dependence 197
Only chondrocytes for chondral layer 197
Chondrocytes for chondral layer and other cell source for subchondral layer 198
Stem cells for chondral layer 199
10.3.1.3 Bilayered Scaffolds with Bioactive Factor Dependence 201
10.3.1.4 Multilayered and Gradient Scaffolds 203
10.3.2 Modulation of Cell Fate and Engineered OC Tissue 204
10.3.2.1 Modulation of Chondrocytes 204
10.3.2.2 Modulation of Stem Cells 206
10.3.2.3 Modulation of In Vivo Engineered Tissue 208
10.3.3 Interface Regeneration 209
10.4 Conclusions 210
References 210
11 Osteochondral Tissue Engineering and Regenerative Strategies 216
Abstract 216
11.1 Introduction 217
11.2 Biomaterials-Based Strategies for OCD Regeneration 218
11.2.1 Strategies for OC Scaffolds Development 218
11.2.2 Bone- and Cartilage-Like Tissues 219
11.2.3 Bone-Like Tissue Plus Chondrocytes Sheets or Layers 220
11.2.4 Bilayered Continuous Scaffolds-Based Strategies 221
11.2.5 Injectable Approaches 224
11.3 Cells, Growth Factors and Gene Therapy for OCD Regeneration 225
11.4 3D In Vitro Cell Culture Methods 227
11.5 Final Remarks and Future Directions 229
Acknowledgments 231
References 231
Meniscus Injuries: Replacement, Repair and Regeneration 237
12 Basics of the Meniscus 238
Abstract 238
12.1 Introduction 238
12.2 The Embryology and Development of the Meniscus 239
12.3 The Gross Anatomy of the Meniscus 240
12.4 The Vascularity of the Meniscus 241
12.5 The Innervation of the Meniscus 242
12.6 The Cells of Meniscus 243
12.7 The Ultrastructure of the Meniscus 244
12.8 The Functions of the Meniscus 244
12.9 Final Remarks 246
Acknowledgments 246
References 246
13 Biomaterials in Meniscus Tissue Engineering 249
Abstract 249
13.1 Introduction 249
13.2 Non-resorbable Polymers 251
13.2.1 Synthetic 251
13.2.1.1 Polyethylene Terephthalate (PET) 251
13.2.1.2 Polytetrafluorethylene Terephthalate (PTFE) 251
13.2.1.3 Poly(Vinyl Alcohol) Hydrogel (PVA-H) 251
13.2.1.4 Polycarbonate-Urethane (PCU) 253
13.3 Resorbable Polymers 255
13.3.1 Synthetic 255
13.3.1.1 Poly(?-Hydroxy Acids) (PHAs) 255
13.3.1.2 Polycaprolactone/Hyaluronic Acid (PCL/HYAFF) 256
13.3.1.3 Polyurethanes (PU) 257
13.3.2 Natural 260
13.3.2.1 Silk 260
13.3.2.2 Gelatin 261
13.3.2.3 Cellulose 262
13.3.2.4 Collagen 263
13.4 Final Considerations 264
Acknowledgments 265
References 265
14 Advanced Regenerative Strategies for Human Knee Meniscus 271
Abstract 271
14.1 Introduction 272
14.2 Bioreactors for Meniscus Tissue Regeneration 274
14.3 Self-Assembling Process for Meniscus Tissue Regeneration 276
14.4 Somatic Gene Therapy for Meniscus Tissue Regeneration 278
14.5 Final Remarks 280
Acknowledgments 281
References 281
Knee Ligament Injuries 286
15 Fundamentals on Injuries of Knee Ligaments in Footballers 287
Abstract 287
15.1 Introduction 288
15.2 Anterior Cruciate Ligament 289
15.2.1 Developments on ACL Assessment 292
15.2.2 Risk Factors 294
15.2.3 ACL Revision Surgery 295
15.2.4 Return to Play 296
15.3 Medial Collateral Ligament 296
15.3.1 Injury Mechanism and Evaluation 298
15.3.2 Treatment Strategy 299
15.4 Posterior Cruciate Ligament 300
15.4.1 Diagnosis, Mechanism of Injury and Classification 301
15.4.2 Treatment Options 303
15.5 Posterolateral Corner Injuries 305
15.5.1 Summary of Anatomy and Biomechanics 305
15.5.2 Clinical Examination 306
15.5.3 Classification 307
15.5.4 Indications for Treatment 307
15.6 Take-Home Message 309
References 309
16 Clinical Management of Ligament Injuries of the Knee and Postoperative Rehabilitation 320
Abstract 320
16.1 Anterior Cruciate Ligament 320
16.1.1 Introduction 320
16.1.2 Anatomy 321
16.1.3 Biomechanics 321
16.1.4 Mechanism of Injury 322
16.1.5 Diagnosis 323
16.1.6 Treatment 324
16.1.7 Rehabilitation 325
16.2 Posterior Cruciate Ligament 326
16.2.1 Introduction 326
16.2.2 Anatomy 326
16.2.3 Mechanism of Injury 327
16.2.4 Diagnosis 327
16.2.5 Treatment 328
16.2.6 Rehabilitation 329
16.3 Medial Collateral Ligament and Posteromedial Corner 330
16.3.1 Introduction 330
16.3.2 Anatomy 330
16.3.3 Biomechanics 330
16.3.4 Mechanism of Injury 331
16.3.5 Diagnosis 331
16.3.6 Treatment 332
16.3.7 Rehabilitation 333
16.4 Lateral Collateral Ligament and Posterolateral Corner 333
16.4.1 Introduction 333
16.4.2 Anatomy 334
16.4.3 Biomechanics 334
16.4.4 Mechanism of Injury 335
16.4.5 Diagnosis 335
16.4.6 Treatment 336
16.4.7 Rehabilitation 337
16.5 Multi-ligament Knee Injuries 338
16.5.1 Introduction 338
16.5.2 Anatomy 338
16.5.3 Diagnosis 338
16.5.4 Treatment 339
16.5.5 Rehabilitation 340
References 341
17 Biomaterials as Tendon and Ligament Substitutes: Current Developments 346
Abstract 346
17.1 Tendon/Ligament Physiology and Properties 347
17.2 Tendon and Ligament Response to Injury and Regeneration 349
17.3 Current Conventional Treatments 350
17.4 Tissue Engineering Strategies for Tendon and Ligament Regeneration 352
17.4.1 Tissue Engineering and Regeneration 352
17.4.2 Cell-Based Strategies for Tendon and Ligament Tissues 353
17.4.3 Design and Fabrication of 3D Sophisticated Scaffolds 355
17.4.3.1 Electrospinning 356
17.4.3.2 Electrochemical Alignment Technique 360
17.5 Conclusions 363
Acknowledgments 364
References 364
18 Ligament Tissue Engineering 369
Abstract 369
18.1 Introduction 369
18.2 Limitations of Current Treatment Options 370
18.3 Ligament Structure 370
18.4 Ligament Healing 371
18.5 Tissue Engineering 372
18.6 Cell Sources for Ligament Tissue Engineering 372
18.6.1 Fibroblasts 373
18.6.2 Mesechymal Stem Cells 373
18.6.3 Studies Comparing Fibroblasts and Mesenchymal Stm Cells 374
18.7 Growth Factors Through Gene Transfer Technology 375
18.8 Scaffolds 376
18.8.1 Natural Scaffolds 377
18.8.2 Synthetic Scaffolds 377
18.8.3 Preclinical and Clinical Studies Using Scaffolds 378
18.9 Bioreactor Systems 379
18.10 Conclusions 380
References 381
19 Regenerative Engineering of the Anterior Cruciate Ligament 386
Abstract 386
19.1 Introduction 387
19.1.1 Structure of the Anterior Cruciate Ligament 388
19.1.2 Constituent Components of Ligaments 389
19.1.3 ACL Reconstruction: Graft Placement and Their Role in the Kinematics of the Knee 392
19.2 Regenerative Engineering Approaches to Enhance Ligament Regeneration 394
19.2.1 Criteria for Ligament Scaffolds 394
19.2.2 Natural Scaffolds 395
19.2.3 Synthetic Scaffolds 397
19.3 Biological Adjuvants for Enhanced Ligament Regeneration 398
19.3.1 Platelet Rich Plasma to Enhance ACL Repair 399
19.3.2 Adipose-Derived Stem Cells 400
19.3.3 Alternative Methods for ACL Reconstruction 401
19.4 Future Trends 402
References 402
Author Index 406