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.

Preface 5
What a Time for Orthopedic Biomaterial Research and Education! 5
Contents 7
Part I: Nanotechnology and Biomimetics 9
Orthopedic Nanomaterials 10
1 Introduction: Nanotechnology and Nanomaterials 10
2 Nanomaterials Enhanced Orthopedic Implants 13
2.1 Significance of the Orthopedic Nanomaterial Surface 16
3 Nanomaterials in Bone Tissue Engineering for Orthopedic Application 19
4 Toxicological Effect of the Nanomaterials for Orthopedic Applications 21
5 Characterization of Orthopedic Nanomaterials 23
5.1 Size, Shape and Topological Information 23
5.1.1 Scanning Electron Microscopy 23
5.1.2 Fluorescence Microscopy 25
5.1.3 Atomic Force Microscopy 25
5.2 Inner View, Crystal Structure, Chemical Information 26
5.2.1 Transmission Electron Microscopy 26
5.2.2 X-Ray Diffraction Spectroscopy 30
5.3 Chemical Bonding Information 30
5.3.1 Fourier Transform Infrared Spectroscopy 30
5.3.2 Raman Spectroscopy 31
6 Summary 31
References 32
Nanotechnology for Reducing Orthopedic Implant Infections: Synthesis, Characterization, and Properties 38
1 Introduction 38
1.1 Current Implants and Implantable Devices 38
2 Implant Biomaterials 39
2.1 Metals 40
2.2 Polymers 41
2.3 Ceramics 44
3 Problems with Conventional Implants 44
3.1 Host Response to Foreign Materials 45
3.2 Bacterial and Biofilm Infections 46
4 Where Bio Meet Nano: The Use of Nanotechnology in Implants 49
5 The Role of Surfaces in Biological Properties 50
5.1 The Effect of Nanotopography on Protein Adsorption 50
5.2 The Effect of Nanotopography on Cellular Functions 53
5.3 The Effect of Nanotopography on Bacterial Attachment 54
6 Nanofabrication Techniques 56
6.1 Nanolithography 56
6.2 Nanofabrication by Deposition Techniques 59
6.3 Nanofabrication by Self-assembly 60
7 Sensors 61
8 Conclusions 63
References 63
Orthopedic Applications of Silver and Silver Nanoparticles 70
1 Introduction 70
2 Antimicrobial Mechanisms, Delivery, and Metabolic Pathways of Ag 73
3 Ag Dressings 75
3.1 In Vitro and In Vivo Studies of Ag Dressings 76
3.2 Clinical Studies 78
4 Ag-Coated Prosthetic Implants 80
4.1 Ag-Coated External Fixation Pins: In Vitro, In Vivo, and Clinical Studies 81
4.1.1 In Vitro and In Vivo Studies 81
4.1.2 Clinical Studies 82
4.2 Ag-Coated Megaprostheses: In Vitro, In Vivo, and Clinical Studies 82
4.2.1 In Vitro and In Vivo Studies 83
4.2.2 Clinical Studies 83
5 Ag-Based Bone Cements 85
6 Summary 87
References 88
Formulation and Evaluation of Nanoenhanced Anti-bacterial Calcium Phosphate Bone Cements 91
1 Introduction 91
2 Materials 93
2.1 Materials 93
2.2 Antibiotics 93
3 Methods 98
3.1 Sample Preparation 98
3.2 HNT Loading 99
3.3 Formulation of CPCs 99
3.4 Scanning Electron Microscopy 99
3.5 Material Testing 100
3.6 Drug Release Assay 101
3.7 Bacterial Culture 101
4 Results and Discussion 102
4.1 Morphology of CPC Scaffolds 102
4.2 Mechanical Properties 103
4.2.1 Compression Strength 103
4.2.2 Flexural Strength 105
4.3 Drug Release Profile 105
4.4 Bacterial Culture 106
5 Conclusions 110
6 Future Work 110
References 111
Biomimetic Orthopedic Materials 115
1 Introduction 115
2 Design Criteria for Engineering Biologically Inspired Orthopedic Materials 117
2.1 Biocompatibility 118
2.2 Biodegradability 119
2.3 Mechanical Properties 120
2.4 Microarchitecture 122
3 Nanofibrous Materials 123
3.1 Self-assembly 123
3.2 Electrospinning 124
3.3 Phase Separation 125
4 Composite and Nanocomposite Materials 126
5 Bulk and Surface Modification 126
6 Delivery of Bioactive Molecules 130
7 Biofabrication 132
7.1 3D Bioprinting 132
8 Current Challenges and Future Perspectives 136
References 137
Hydroxyapatite: Design with Nature 146
1 Biological Hydroxyapatite 146
2 Synthetic Methods 149
3 Cellular Response 151
3.1 Hydroxyapatite Bioceramic Induced Osteogenic Differentiation 152
3.2 HANPs Induced Cancer Cell Apoptosis 153
4 Applications 155
4.1 In the Form of Bioceramics for Orthopedic Reconstruction 156
4.2 Incorporation with Polymers as Scaffolds for Bone Substitution 157
4.3 Coating for Metallic Implants 159
4.4 Drug Delivery Carriers for Bone Formation 159
5 Conclusions 161
References 161
Calcium Phosphate Coatings for Metallic Orthopedic Biomaterials 171
1 Introduction 171
2 Metals for Biomedical Implant Applications 172
3 Surface Properties of the Implant Material 173
4 Calcium Phosphate Coatings on Biomedical Metals 175
4.1 Biocompatibility: Osteointegration 176
4.2 Corrosion Resistance 178
4.3 Antibacterial Property 179
5 Conclusion 182
References 183
Part II: Polymer Biomaterials 188
Collagen-Based Scaffolds for Bone Tissue Engineering Applications 189
1 Introduction 189
2 Bone Tissue Engineering 192
2.1 Crosslinking Techniques for Collagen Scaffolds 194
2.2 Collagen-Based Composite Materials 197
3 Collagen-Based Scaffold Fabrication Methods for Bone Tissue Engineering 200
3.1 Hydrogels 200
3.2 Plastic Compression 200
3.3 Freeze Drying 205
3.4 Compression Molding and Porogen Leaching 207
3.5 Electrospinning 208
3.6 Electrochemical Fabrication 210
4 In Vivo Bone Regeneration Using Collagen-Based Scaffolds 212
5 FDA Approved Collagen-Based Materials 215
6 Conclusions and Future Outlook 216
References 218
Poly(ethylene glycol) and Co-polymer Based-­Hydrogels for Craniofacial Bone Tissue Engineering 227
1 Introduction 227
2 2D Versus 3D Cell Culture and Response 230
3 PEG-Hydrogels for In Situ Cell Culture and Growth Factor Delivery 231
4 Cross-Linking Mechanisms of PEG-Hydrogels 232
4.1 Step-Growth Polymerization 232
4.2 Chain-Growth Polymerization 232
4.3 Mixed-Mode Polymerization 233
5 Bioactive Modifications of PEG-Hydrogels for Craniofacial Tissue Engineering Applications 235
6 Degradation Behavior of PEG-Hydrogel Scaffolds 235
7 Poly(ethylene glycol) Diacrylate (PEGDA) for Craniofacial Tissue Engineering Applications 237
7.1 Designing Fast-Degrading Visible Light-Cured Thiol-­Acrylate Hydrogels for Craniofacial Tissue Engineering 238
7.2 BMP2-Loaded Visible Light Cured Thiol-Acrylate Hydrogels 240
7.3 Biodegradable Visible Light Cured Thiol-Acrylate Hydrogel as a Stem-Cell Carrier for Craniofacial Bone Tissue Engineering 243
8 Conclusion and Future Insight 244
References 245
Peptides as Orthopedic Biomaterials 249
1 Introduction 249
2 Pathways for Peptide Delivery 250
3 Peptides for Orthopedic Applications 254
3.1 Antimicrobial Peptides 254
3.2 Tissue Engineering 259
3.3 Arthritis 263
3.4 Bone Tumor 263
3.5 Biomarkers for Diagnostic 264
3.6 Miscellaneous 265
4 Challenges 265
5 Summary 266
References 267
Part III: Degradable Metal Biomaterials 274
Biodegradable Metals for Orthopedic Applications 275
1 Introduction 275
2 Biodegradable Mg Based Metals 276
2.1 Biodegradation Reaction 277
2.2 Key Factors 277
2.2.1 Effect of Body Environment on Degradation Behavior of Mg Based Metals 277
2.2.2 Effect of In Vivo on Stress Corrosion Behavior of Mg Based Metals 278
2.2.3 Effect of Other Features on Corrosion Behavior of Mg Based Metals 278
2.3 Biofunctions 279
2.3.1 Promoting Osteogenesis Function 279
2.3.2 Antimicrobial 283
2.3.3 Inhibiting Tumor Cell Survival 285
3 Applications for Orthopedics 288
3.1 Bone Fixation 288
3.2 Bone Substitute 292
3.3 Osteomyelitis Treatment 297
3.4 Mg Coating 298
4 Conclusions 301
References 302
Development of Biodegradable Zn-Based Medical Implants 310
1 Introduction 310
2 Pure Zn 311
3 Zn-Based Binary Alloy 314
3.1 Microstructures 314
3.2 Mechanical Properties 314
3.3 Degradation Behavior 315
3.4 Biocompatibility 317
3.4.1 In vitro 317
3.4.2 In vivo 318
4 Zn-Based Ternary Alloy 320
4.1 Microstructures 320
4.2 Mechanical Properties 322
4.3 Degradation Behavior 322
4.4 Biocompatibility 323
5 Concluding Remarks and Perspectives 326
References 326
Surface Modification and Coatings for Controlling the Degradation and Bioactivity of Magnesium Alloys for Medical Applications 329
1 Introduction 329
1.1 Magnesium and the Current Orthopedic Materials 329
1.2 There Is No Such Thing as Permanent Implants 330
1.3 Why Use Biodegradable Implants? 330
1.4 The Advantages of Magnesium 330
1.5 The Challenges of Magnesium 331
1.6 Coatings Can Address Many Challenges 334
2 Substrate Preparations 335
3 Structure and Physical Properties of Coatings 336
4 Surface Modification of Magnesium 338
4.1 Chemical Surface Modification 338
4.2 Anodization 339
4.3 Micro-Arc Oxidation 339
5 Deposited Coatings 339
5.1 Calcium Phosphate Coatings 340
5.2 Polymer Coatings 341
5.2.1 Commonly Used Polymer Coatings 341
5.2.2 Overview of Polymer Properties 343
5.2.3 Methods of Depositing Polymer Coatings 345
Dip Coating 345
Spin Coating 346
Electrospinning 346
Electrodeposition 346
6 Composite Coatings 347
6.1 Hydroxyapatite Composite Coatings 347
6.2 Polymer Coatings and Surface Modifications 349
7 Incorporation of Bioactive Factors into Coatings 349
8 Summary 350
References 350
Part IV: Biomaterial Implants and Devices 362
Materials for Orthopedic Applications 363
1 Orthopedic Implant Devices for Prolonged and Permanent Contact 363
1.1 Bone Attachment Devices and Stabilizers 367
1.2 Artificial Joints 374
1.3 Artificial Ligaments and Tendons 381
1.4 Artificial Spine Devices 383
1.5 Biologics and Tissue Regeneration Inducers 387
2 Implant Delivery Systems and Surgical Instrumentations 391
3 Conclusion and Future Directions 392
References 392
Composite Orthopedic Fixation Devices 395
1 Introduction 395
2 Development of Internal Fixation Devices 397
2.1 Implant Design 397
2.2 Tissue Interactions and Cytotoxicity 400
3 Current Metal Fixation Plates 400
4 Composite Fixation Devices 403
4.1 Non-Load-Bearing Composites 404
4.2 Composites for Load-Bearing Fractures 409
4.2.1 Resorbable Polymer-Based Composites 409
4.2.2 Partially Resorbable Composites 415
4.2.3 Resorbable Metals 415
5 Conclusions 416
References 417
PEEK Titanium Composite (PTC) for Spinal Implants 422
1 Introduction 423
2 Manufacturing and Applications 424
2.1 Manufacturing 424
2.2 PTC Applications 426
3 Mechanical Properties 426
3.1 Methods 426
3.1.1 Testing Setup 426
3.1.2 Statistical Analysis 428
3.2 Results 429
4 Surface Topographic Characterization 430
4.1 Methods 430
4.2 Results 431
5 In Vitro Studies 433
5.1 Characterization of Ti 2D and 3D Substrates with SAOS2 Cells 433
5.1.1 Methods 433
Substrates 433
Cells 434
Cell Seeding and Culture 434
Evaluation of Cell Viability and Morphology on Ti Substrates 435
Rabbit Polyclonal Antisera and Purified Proteins 435
Extraction of ECM Proteins from the Cultured Substrates and ELISA 436
Indirect Immunofluorescence Staining 436
ALP Activity 437
Statistical Analysis 437
5.1.2 Results 437
SAOS2 Cell Viability and Morphology 437
Characterization of the Bone Matrix Deposition 438
5.2 Characterization of Ti 3D and PEEK Substrates with Human MG63 Cells 439
5.2.1 Methods 439
Substrates 439
Cells and Assays 440
Statistical Analysis 440
5.2.2 Results 441
Comparisons of Secretions from Ti/PEEK Substrate Versus Control Surfaces 441
Comparisons of Secretions from Ti 3D Versus PEEK Surfaces 442
6 In Vivo Animal Studies 442
6.1 Characterization of Ti 3D and PEEK Substrates in a Rabbit Animal Model 442
6.1.1 Methods 442
Substrates for Implantation 442
Animals 443
Surgery 443
Assessment 443
Statistical Analysis 444
6.1.2 Results 444
Bone Apposition and Ingrowth in the Cortical Region 444
Biocompatibility and Irritancy 445
6.2 Evaluation of a PTC Interbody Device in an Ovine Lumbar Fusion Model 445
6.2.1 Methods 445
Animals, Devices and Surgery 445
Assessments 446
Statistical Analysis 448
6.2.2 Results 449
Animal Health 449
Biomechanical Properties 449
MicroCT 450
Histology 450
Fusion Score 452
7 Discussions 452
8 Conclusions 456
References 456
Advances in Bearing Materials for Total Artificial Hip Arthroplasty 461
1 Introduction 461
2 History of the Development of Artificial Hip Joints 462
3 Ultra-high Molecular Weight Polyethylene 462
4 Metallic Materials 463
5 Ceramics 464
5.1 Alumina 464
5.2 Zirconia 465
5.3 Silicon nitride 466
5.4 Alumina-Zirconia Composites 466
6 Ultra-hard Coatings on Metals 468
7 Oxinium™ 469
8 Rationale for the Design of a New Kind of Ceramic/Metal Hybrid Artificial Joint 470
8.1 Selection and Design of Materials 470
8.2 Rationale for the New Design of an Artificial Hip Joint 471
8.3 Science and Technology of a Dense ?-alumina Layer on the Ti Alloy 472
8.3.1 Formation of Al Layer on the Ti Alloy Substrate 473
8.3.2 Formation of Reaction Layer at the Alumina-Ti Alloy Interface 473
8.3.3 Formation of an Alumina Layer on the Ti Alloy Substrate 475
8.3.4 Adhesion of an Alumina Layer with the Ti Alloy Substrate 479
8.3.5 Dense Alumina Layer on a Ti Alloy by Cold Metal Transfer and MAO Methods 480
9 Summary and Conclusions 482
References 483
Bone Grafts and Bone Substitutes for Bone Defect Management 489
1 Introduction 489
2 Bone Grafts and Substitutes for Bone Defect Treatments 490
2.1 Natural Bone Grafts 491
2.1.1 Autologous Bone Grafts 491
2.1.2 Allogeneic Bone Grafts 493
2.2 Synthetic Bone Graft Substitutes 494
2.2.1 Calcium Sulfate 495
2.2.2 Calcium Phosphate Ceramics (CaP Ceramics) 495
2.2.3 Calcium Phosphate Cements (CPC) 497
2.2.4 Bioactive Glass 498
2.2.5 Poly(Methyl Methacrylate) (PMMA) Bone Cement 500
3 The Adoption of Growth Factors on Bone Defect Management 501
3.1 Bone Morphogenetic Proteins (BMPs) 501
3.2 Fibroblast Growth Factors (FGFs) 504
3.3 Vascular Endothelial Growth Factor (VEGF) 504
3.4 Parathyroid Hormone (PTH) 505
3.5 Platelet-Rich Plasma (PRP) 507
4 The Adoption of Bioinorganic Ions on Bone Regeneration 508
4.1 Silicon (Si) 508
4.2 Strontium (Sr) 512
4.3 Magnesium (mg) 515
4.4 Zinc (Zn) 519
4.5 Copper (Cu) 520
4.6 Other Ions 520
5 Conclusion and Future Directions 522
References 523
Novel Composites for Human Meniscus Replacement 540
1 Introduction 540
2 Methods 541
2.1 Design of the Mold 541
2.2 Composite Preparation 541
2.3 Mechanical Evaluation 543
2.4 Microstructural Analysis 544
2.5 Meniscal Prosthesis Production 544
2.5.1 Injection Molding Machine 544
2.5.2 Meniscal Prosthesis Fabrication 545
2.6 Friction and Wear Tests of Meniscal Prosthesis 546
2.6.1 Experimental Technique 546
2.6.2 Description of the Test 547
2.6.3 Friction Measurements 548
2.6.4 Wear Measurements 549
2.7 Surface Characterization 549
3 Results and Discussion 551
3.1 Tensile and Compression Tests 551
3.2 Friction Test for the Produced Meniscal Prosthesis 553
3.3 Wear Test of the Produced Meniscus 557
4 Conclusion 559
References 559
Biomaterial-Mediated Drug Delivery in Primary and Metastatic Cancers of the Bone 562
1 Introduction 562
2 Classifications of Cancers That Affect the Bone 564
2.1 Primary Bone Cancer 564
2.2 Bone Metastatic Disease 565
3 Bone Biology and Remodelling 565
4 The Pathophysiology of Bone Metastatic Disease 568
5 Diagnosis and Treatment 571
6 Application of Biomaterials in Primary and Metastatic Cancers Affecting the Bone 573
6.1 Biomaterials in Drug Delivery 573
6.1.1 Drug Delivery in Primary and Metastatic Cancers Affecting the Bone 573
6.1.2 Polymeric Biomaterials in Drug Delivery 574
6.1.3 Inorganic Biomaterials in Drug Delivery 576
6.2 Targeted-Drug Delivery 578
6.2.1 Increasing Successful Localisation 578
6.2.2 Smart Drug Delivery 579
6.2.3 Targeting Moieties 580
7 Techniques to Augment Delivery 584
8 Conclusions and Future Perspectives 587
References 589
Index 598