Orthopedic Biomaterials (eBook)

Bingyun Li is a full Professor with tenure at School of Medicine West Virginia University. He is a member of the Society for Biomaterials (SFB), Orthopedic Research Society (ORS), American Society for Microbiology (ASM), Materials Research Society (MRS), American Chemical Society (ACS), International Chinese Musculoskeletal Research Society (ICMRS), and Chinese Association for Biomaterials (CAB). Professor Li has served as topic chair of Infection and Inflammation of the ORS Program Committee, vice-chair and chair of Orthopedic Biomaterials Special Interest Group of SFB, Chief Editor of ICMRS Newsletter, and inaugural treasurer of CAB. Professor Li’s research focuses on advanced materials, nanomedicine, infection, immunology, and drug delivery. He has supervised 84 trainees, and his lab group has published more than 76 peer-reviewed articles, nine book chapters, 12 provisional/full patents, and 122 abstracts. Professor Li has given 48 invited talks and has received multiple prestigious awards including the Berton Rahn Prize from AO Foundation, the Pfizer Best Scientific Paper Award from Asia Pacific Orthopedic Association, and the Collaborative Exchange Award from Orthopedic Research Society.Thomas Webster is the Chemical Engineering Department Chair and Art Zafiropoulo Endowed Chair at Northeastern University. Prof. Webster has graduated 144 students. His lab group published 9 textbooks, 48 book chapters, 403 articles, and 32 provisional/full patents. Prof. Webster has received numerous honors: 2012, Fellow, American Institute for Medical and Biological Engineering; 2013, Fellow, Biomedical Engineering Society; 2015, Wenzhou 580 Award; 2015, Zheijang 1000 Talent Program; 2016, IMRC Chinese Academy of Science Lee-Hsun Lecture Award; 2016, Fellow, Biomaterials Science and Engineering; and 2016, Acta Biomaterialia Silver Award. He also frequently appears on the BBC, NBC, ABC, Fox, National Geographic, Discovery Channel and many other news outlets talking about science. Prof. Webster was also recently inducted as a Fellow into the National Academy of Inventors based on the formation of 11 companies with 4 FDA approved products in orthopedics. Prof. Webster was also recently inducted as a Fellow into the National Academy of Inventors based on the formation of 11 companies with 4 FDA approved products in orthopedics.

Preface 5
Contents 6
Part I: Design, Manufacturing, Assessment, and Applications 8
Nanotechnology for Orthopedic Applications: From Manufacturing Processes to Clinical Applications 9
1 Introduction 9
2 The Extracellular Matrix (ECM) 9
2.1 ECM Composition 10
2.2 The ECM as a Molecular Reservoir 10
2.3 Cell-ECM Interactions 11
2.4 Bone 13
2.4.1 Cortical Bone 13
2.4.2 Cancellous Bone 13
3 Tissue Engineering 14
3.1 Nanotechnology for Tissue Engineering 14
3.2 Control of Cell Functions Using Nanotechnology 16
3.3 Cell Sensitivity to Nanofeatures 17
3.4 Important Features of Scaffolds for Tissue Engineering 17
3.5 Materials for Scaffold Construction 17
4 Unmet Clinical Need 18
4.1 Substrate Properties for Osseointegration 19
4.2 Substrate Properties to Resist Bacterial Infection 19
4.2.1 Shot Peened 316 L Stainless Steel 20
4.2.2 Electrophoretic Deposition 21
5 Conclusions 22
References 23
Additive Manufacturing of Orthopedic Implants 27
1 Introduction 27
2 Additive Manufacturing Techniques 28
2.1 Binder Jetting 29
2.2 Directed Energy Deposition (DED) 31
2.3 Powder Bed Fusion (PBF) 32
2.4 Material Extrusion 34
3 Additively Manufactured Biomaterials 35
3.1 Metallic Biomaterials 35
3.1.1 Stainless Steel 36
3.1.2 Co-Cr Alloys 37
3.1.3 Titanium Alloys 38
3.1.4 Tantalum 39
3.2 Other Biomaterials 39
3.2.1 PEEK 39
3.2.2 Ceramics 40
4 AM Design Considerations 41
4.1 Patient-Specific Design Procedures 43
4.2 Porosity 44
4.3 Clinical Applications 45
4.4 Patient Variability 45
4.5 Shoulder and Other Joint Replacements 46
4.6 Fracture Fixation 49
4.7 Large Bone Defects 52
4.8 Surgical Guides 53
4.9 Additional Clinical Examples 54
5 Summary 55
References 57
3D Printed Porous Bone Constructs 62
1 Introduction 62
2 3D Printing Techniques 63
3 Porous Materials for Cell Growth 65
4 3D Printing of Porous Ceramic Materials 65
5 3D Printing of Porous Metal Materials 67
6 3D Printing of Porous Polymer Materials 68
7 Conclusions 69
References 69
Biopolymer Based Interfacial Tissue Engineering for Arthritis 72
1 Introduction 72
2 Anatomy of Osteochondral Tissue Interface 73
3 Conventional Vs. Interfacial Tissue Engineering 75
4 Polymeric Biomaterials for Interfacial Tissue Engineering 78
5 Design Considerations for Interfacial Tissue Engineering 83
5.1 Stratified Scaffold Design 83
5.2 Gradient Scaffold Design 85
6 Present Clinical Status of Interfacial Tissue Engineering 87
7 Future Perspectives of Interfacial Tissue Engineering in Orthopedic Applications 87
8 Conclusion 88
References 88
Performance of Bore-Cone Taper Junctions on Explanted Total Knee Replacements with Modular Stem Extensions: Mechanical Disassembly and Corrosion Analysis of Two Designs 94
1 Introduction 94
2 Materials and Methods 96
2.1 Implant Retrieval and Archiving 96
2.2 Assessment of Surface Corrosion Area 98
2.3 Damage Mode Characterization 102
2.4 Data Analysis 105
3 Results 105
4 Discussion 109
4.1 Effects of Design and Modes of Corrosion 109
4.2 Effects of Patient Factors and Anatomical Location 110
4.3 Mechanical Disassembly and Surface Corrosion Area 110
4.4 Limitations 111
5 Conclusion 111
References 112
Wear Simulation Testing for Joint Implants 115
1 Introduction: Why Joint Simulator? 115
2 What Is a Joint Simulator? 116
3 Types of Joint Simulators 117
4 Current Wear Simulation Standards 120
5 The Achievement of Wear Simulation 121
6 The Limitation of Wear Simulation 122
7 Conclusions 123
References 124
Mechanical Stimulation Methods for Cartilage Tissue Engineering 126
1 Cartilage Anatomy 126
2 Cartilage as a Material 127
3 Cartilage Tissue Engineering 129
4 Dynamic Loading Scenarios for Mechanical Stimulation 132
4.1 Compression 132
4.1.1 Confined Compression 133
4.1.2 Unconfined Compression 133
4.1.3 Indentation 135
4.2 Tension 135
4.2.1 Uniaxial 135
4.2.2 Biaxial or Multiaxial 136
4.3 Shear 136
4.3.1 Hydrodynamic Shear 137
4.3.2 Mechanical Shear 137
4.4 Friction 138
4.5 Vibration 139
4.5.1 High-Frequency Ultrasonic Vibration 139
4.5.2 Lower-Frequency Mechanical Vibrations 139
5 General Drawbacks of Mechanical Stimulation 140
6 Mixed Mode Loading 142
6.1 Compression and Shear 143
6.2 Compression and Vibration 143
7 Future Directions 145
References 146
Mechanically Assisted Electrochemical Degradation of Alumina-TiC Composites 151
1 Introduction 151
2 Methods and Materials 154
2.1 Brushing Abrasion Setup 154
2.2 Sample Preparation 155
2.3 Electrochemical Measurements 156
2.4 Brushing Abrasion Testing 156
2.4.1 Effect of Brushing Acceleration and Speed 156
2.4.2 Effect of Temperature 157
2.4.3 Effect of Environment 157
2.5 Electrochemical Impedance Study 157
2.6 Surface Characterization 158
2.7 Chemical Analysis 158
3 Results and Discussion 159
3.1 Electrochemical Response to Brushing Abrasion 159
3.2 Surface Characterization 162
3.3 Chemical Analysis 165
3.4 Electrochemical Impedance Data Analysis 167
3.5 Understanding the Degradation Mechanism of Alumina-TiC Composite 169
4 Conclusions 171
References 171
Part II: Biology and Clinical and Industrial Perspectives 174
Biomaterials in Total Joint Arthroplasty 175
1 Introduction 175
2 Stability 177
3 Sterility 178
4 Survivability 179
5 Bearing Surfaces: Polyethylene 179
5.1 Polyethylene Then 179
5.2 Polyethylene Now 181
5.3 Polyethylene: Case Reports 1–4 (Figs. 3, 4, 5 and 6) 184
6 Bearing Surfaces: Metal 187
6.1 Metal Then 187
6.2 Metal Now 189
6.3 Metal on Metal: Case Report 5 and 6 (Figs. 7 and 8) 190
7 Bearing Surfaces: Ceramic 192
7.1 Ceramic Then 192
7.2 Ceramic Now 193
7.3 Ceramic: Case Report 7 (Fig. 9) 194
8 Conclusion 195
References 195
Modulating Innate Inflammatory Reactions in the Application of Orthopedic Biomaterials 199
1 Introduction 200
2 Inflammation and Immunomodulating Strategy 201
2.1 Innate Immune Response and Macrophages 201
2.2 Macrophage Polarization 202
2.3 Interaction Between Macrophages and Orthopedic Biomaterials 203
2.4 Modulation of Macrophage-Mediated Pro-Inflammatory Response 203
3 Sequential Modulation of Inflammatory Response for Optimal Bone Regeneration/Osseointegration 206
3.1 Essential Role of Acute Inflammation in Bone Regeneration 206
3.2 Transition of Macrophage Polarization Status for Optimal Bone Formation 207
4 Application of Immunomodulating Reagents on Orthopedic Biomaterials 208
4.1 Protein-Based Biomolecules 209
4.2 Nucleic Acid 209
4.3 Small Molecules 210
4.4 Cell-Based Therapy 211
5 Conclusion 211
References 212
Anti-Infection Technologies for Orthopedic Implants: Materials and Considerations for Commercial Development 219
1 Introduction 219
2 Working Theories of Implant Related Infection 220
3 Current Clinical Options 222
4 Biomaterial Strategies for Infection Prevention 222
4.1 Passive Surface Modification 223
4.1.1 Nanotopography 224
4.1.2 Photocatalytic Titanium Oxide 224
4.1.3 Covalently Bound Antimicrobials 225
4.2 Active Surface Modification 226
4.2.1 Antibiotic Bone Cement 226
4.2.2 Antibiotic Coated Implants 227
4.2.3 Bone Graft Substitutes with Antibiotics 228
4.2.4 Antimicrobial Silver Coatings 229
Silver Antimicrobial Mechanism of Action 229
Current Commercial Products with Antimicrobial Silver 229
Silver Coating Technologies in Development 230
Potential for Toxicity of Silver in Orthopedics 231
4.2.5 Antimicrobial Iodine Coatings 232
4.3 Perioperative Local Antibiotics 232
4.3.1 Direct Local Application of Antibiotics 232
4.3.2 Local Antibiotic Carriers 233
5 Regulatory and Commercial Considerations 234
5.1 Preclinical Data 234
5.2 Regulatory and Market Hurdles 235
6 Summary 236
References 236
Platelet Rich Plasma: Biology and Clinical Usage in Orthopedics 243
1 Introduction 243
2 Biology of Platelet Rich Plasma 244
2.1 What is PRP (PRP Definition)? 244
2.2 Principles for PRP Isolation and Classification 244
2.2.1 Principle for PRP Isolation 246
2.2.2 PRP Classification 247
2.3 Biologics of PRP 249
2.3.1 Platelet and Platelet Released Factors 250
Platelet Alpha Granules 251
Dense Granules 251
The Lambda Granules 252
Regulation of Platelet Secretion 252
2.3.2 Leukocytes 253
2.3.3 Red Blood Cells 253
2.3.4 Extracellular Vehicles (EVs) 254
3 Clinical Applications of Platelet-Rich Plasma in Orthopedics Surgery 255
3.1 Tendons 256
3.2 ligament 268
3.3 Cartilage 271
3.4 Muscle 276
3.5 Minimum Information for Studies Evaluating Biologics in Orthopedics (MIBO) 278
3.6 In Summary 279
References 279
Bioresorbable Materials for Orthopedic Applications (Lactide and Glycolide Based) 287
1 Introduction 287
2 Bioresorbable Polymers 290
2.1 Poly(glycolic acid) (PGA) 290
2.2 Poly(lactic acid) (PLA) 291
2.3 Poly(lactic-co-glycolic acid) (PLGA) 293
2.4 Polycaprolactone (PCL) 293
2.5 Polydioxanone (PDO) 294
3 Bioresorbable Degradation 295
3.1 Factors Affecting Degradation 297
3.1.1 Inherent Polymer Factors 297
3.1.2 Secondary Ingredients 299
4 Mechanical Performance 299
4.1 Factors Affecting Mechanical Performance 300
4.2 Mechanical Enhancement via Additives. 301
4.3 Effect of Implant Design on Mechanical Performance 302
5 Bioactivity 303
5.1 Inorganic Additives 304
5.1.1 Calcium Phosphate Based 304
Hydroxyapatite (HA) 304
Tricalcium Phosphate (TCP) 305
Biphasic Calcium Phosphate (BCP) 305
Calcium Sulfate 305
5.2 Other Additives 306
6 Biocompatibility 307
7 Processing and Fabrication 308
7.1 Material Effect on Pre-Processing and Processing 309
7.2 Conventional Processing Methods 310
7.2.1 Extrusion 310
7.2.2 Injection Molding 313
7.2.3 Compression Molding 315
7.3 Novel Methods (Additive Manufacturing) 316
7.3.1 Fused Deposition Modelling (FDM) 316
7.3.2 Selective Laser Sintering (SLS) 318
7.4 Other Methods 320
7.4.1 Electrospinning 321
7.5 Effect of Post-Processing 322
7.5.1 Annealing 322
7.5.2 Sterilization 323
8 Current Applications 324
8.1 Craniomaxillofacial (CMF) 326
8.2 Sutures and Suture Anchors 327
8.3 Interference Screw 330
8.4 Distal Radius Plate 332
9 Regenerative Medicine 333
10 Conclusion 336
References 336
The Role of Polymer Additives in Enhancing the Response of Calcium Phosphate Cement 345
1 Introduction 345
2 Advantages of Calcium Phosphate Cement 347
3 Disadvantages of Calcium Phosphate Cement 348
4 Calcium Phosphate Applications 348
5 Calcium Phosphate Additives and Setting Time 349
5.1 Chitosan 350
5.2 Fibrin Glue 351
5.3 Gelatin 351
5.4 Collagen 352
5.5 Polyethylene Glycol (PEG) 352
6 Calcium Phosphate Additives: Material and Mechanical Properties 352
6.1 Natural Polymers 352
6.1.1 Alginate 353
6.1.2 Chitosan 353
6.2 Synthetic Polymers 354
6.2.1 Polyacrylic Acid 354
6.2.2 Polycaprolactone 354
6.2.3 Polylactic Acid (PLA) 355
6.2.4 Poly(lactic-co-glycolic) Acid 356
6.3 Carbon Nanotubes, Clay Nanoparticles and Graphene 357
6.3.1 Carbon Nanotubes 357
6.3.2 Clay Nanoparticles 357
6.3.3 Halloysite Nanotubes 357
6.3.4 Laponite 358
6.3.5 Montmorillonite (MT) 359
6.3.6 Graphene 359
6.4 Natural Fibrous Material 360
6.4.1 Cellulose 360
6.4.2 Collagen 360
7 Calcium Phosphate: Injectability 360
8 Calcium Phosphate: Biological Response 361
8.1 CPC/Growth Factor/Polymer Composites for Cell Growth and Functionality 361
8.2 CPC/polymer Composites for Cell Encapsulation 363
8.3 Bioactive Glass and Silica Materials 365
8.3.1 Bioactive Glass 365
8.3.2 Silica Materials 365
8.4 Metal Nanoparticles 366
8.4.1 Copper and Zinc 366
8.4.2 Magnesium 366
8.4.3 Zirconia 367
9 Future Studies 367
References 368
Biological Fixation: The Role of Screw Surface Design 380
1 Introduction 380
2 History 382
3 A Brief Review of Common Orthopedic Materials 385
4 A Brief Overview of Peri-implant Bone Healing 386
5 How Topography Affects Anchorage of an Implant in Bone 388
5.1 Implant Surface Nanotopography 389
5.2 Implant Surface Microtopography 392
5.3 Implant Macrotopography and Geometry 393
6 Conclusion 395
References 396
Fracture Fixation Biomechanics and Biomaterials 400
1 Clinical Aspects 400
1.1 Introduction 400
1.2 Types of Implants 401
1.3 Anatomical Constraints 404
2 Fracture Healing Biology 405
2.1 Fracture Healing 405
2.2 Infection 408
3 Biomechanics 408
3.1 Implant Loading 408
3.2 Implant Stress and Failure 409
3.3 Fracture Gap Strain 411
3.4 Biomechanical Variables 413
4 Biomaterials 414
4.1 Stainless Steel Vs. Titanium alloys & Other Materials
4.2 Biocompatibility 414
4.3 Corrosion 415
5 Experimental and Computational Modeling of Fracture Fixation Mechanics 416
5.1 Experimental 417
5.2 Computational 418
6 Internal Plating 419
7 Intramedullary Nailing 421
8 Perspective 423
References 424
Biomaterials for Bone Tissue Engineering: Recent Advances and Challenges 428
1 Introduction 428
2 Tissue Engineering 429
3 Bone 430
3.1 Structure and Composition of Bone 430
3.2 Types of Bone 430
4 Stem Cells for Tissue Engineering 431
4.1 Embryonic Stem Cells 431
4.2 Adult Stem Cells 432
4.3 Mesenchymal Stem Cells (MSCs) 432
5 Scaffold 432
6 Scaffold Fabrication Techniques 433
6.1 Particulate-Leaching Technique 434
6.2 Gas Foaming 434
6.3 Lyophilization 434
6.3.1 Solid-Liquid Phase Separation 434
6.3.2 Liquid-Liquid Phase Separation 435
6.4 Electro-Spinning 435
6.5 Solid Freeform Fabrication Technique (SFFT) 436
7 Structural Design 437
7.1 Porosity 437
7.2 Pore Size 437
8 Mechanical Properties 438
9 Composite Scaffold Material 439
9.1 Synthetic Biopolymer/CaP Composite Scaffold 440
9.2 Natural Biopolymer/Bioactive Ceramic Based Composite 441
10 Challenges and Opportunities 444
10.1 Mechanical Integrity of Porous Scaffolds 444
10.2 In vitro Degradation 445
10.3 In vitro and In vivo Characterization 445
11 Discussion and Future Aspects 445
References 446
Progress of Bioceramic and Bioglass Bone Scaffolds for Load-Bearing Applications 452
1 Introduction 452
2 Design Concepts 453
2.1 Microstructure Design: Micropore Size, Microporosity, Grain Size/Morphology and Second Phase 454
2.1.1 Pore Size 454
2.1.2 Porosity 456
2.1.3 Grain Size and Morphology 459
2.1.4 Second Phase Teinforcement 459
2.2 Macrostructure Design: Macropore Shape, Pore size, Macroporosity and Pore Connecting Part Width 460
2.2.1 Pore Shape 460
2.2.2 Pore Size and Pore Connecting Part Width 462
2.2.3 Macroporosity 463
3 Manufacturing Methods 463
3.1 3D printing 464
3.2 Freeze Casting 468
3.3 Slip Casting (Polymer Template Burn-Out) 471
3.4 Thermally Bonding of Particles 472
4 In Vitro Characterization of Load-Bearing Capacity 473
5 In Vivo Assessment via Load Bearing Bone Defect Model 478
6 Bioinspiration Design and Future Perspectives 479
References 480
Index 486