Biomedical Materials (eBook)

A Historical Perspective on the Developmentof Biomedical Materials 5
Contents 8
Contributors 19
Part I The Fundamental Properties of the Materials Usedin Medicine and Dentistry 22
1 Ceramics and Glasses 23
1.1 Introduction 23
1.2 What Is a Ceramic? 24
1.3 Ceramic Processing 25
1.4 Powder Processing 25
1.5 Deformation and Fracture 27
1.6 Transformation Toughening 29
1.7 Pressureless Sintering 30
1.8 Isostatic Pressing 30
1.9 Liquid Phase Sintering 32
1.10 Tape Casting 32
1.11 Costs of Powder Processing 33
1.12 Porous Ceramics 33
1.12.1 BurPS 33
1.12.2 Foamed Slips 34
1.12.3 Reticulated Foams 34
1.13 Measurement of Porosity in Porous Ceramics 35
1.14 Surface Engineering 36
1.14.1 Ion Implantation 37
1.14.2 Thermal Spray Coatings 37
1.15 Glasses and Glass-Ceramics 39
1.15.1 Glasses 39
1.15.2 Glass-Ceramics 41
1.15.3 Bioceramics 42
1.15.4 Bone 43
1.15.5 Medical Ceramics 45
1.15.6 Biomedical Use of Bioceramics 46
1.15.7 Alumina 46
1.15.8 Zirconia 48
1.15.9 Hydroxyapatite 49
1.15.10 Porous Bioceramics 50
1.16 Functional Gradient Materials 52
1.17 Bone Morphogenetic Proteins 53
1.18 Hydroxyapatite Coatings 54
1.19 Bioactive Glasses 56
1.20 Conclusion 57
References 57
2 Metallic Biomaterials 60
2.1 Introduction Why Metals? 60
2.2 Metallic Interatomic Bonding 61
2.3 Crystal Structures Atom Packing in Metals 61
2.4 Phase Transformations Diffusive and Displacive 62
2.5 Diffusion in Metals 65
2.6 Interatomic Forces and Elastic Moduli ( Structure-Insensitive Properties) 67
2.7 Plastic Deformation and Structure-Sensitive Properties 69
2.8 Corrosion Resistance 73
2.9 Metals and Processes for Implant Fabrication 73
2.10 Austenitic Stainless Steel (ASTM F 138/139, F 1314, F 1586, F 2229) American Society for Testing and Materials recommended standards 74
2.11 Co-based Alloys 77
2.12 Cast CoCrMo (ASTM F 75) 77
2.13 Wrought CoCrMo (Low- and High-Carbon) (ASTM F 799, F 1537) 81
2.14 Surface Modification of CoCrMo Implants Porous Coatings for Bone Ingrowth 83
2.15 Other Co-containing Implant Alloys (ASTM F 562, F 90, F 563, F 1058) 85
2.16 Titanium-Based Alloys 86
2.17 Commercial Purity Ti 87
2.18 ( ) Ti Alloys 88
2.19 -Ti and Near -Ti Alloys 90
2.20 Zr-Nb Alloy 91
2.21 Ni-Ti Alloys (Nitinol) 92
2.22 Tantalum 93
2.23 Platinum, Platinum-Iridium 94
2.24 Dental Alloys 94
2.25 Dental Amalgams 95
2.26 Dental Casting Alloys (Au-based, Co- and Ni-based, Ti-based) 95
2.27 Wrought Dental Alloys 96
2.28 New Directions 97
References 97
3 Polymeric Biomaterials 101
3.1 Introduction 101
3.2 Nomenclature 101
3.3 Biopolymer in Medical Applications 101
3.4 Inert Polymers 104
3.4.1 Silicones 105
3.4.2 Polyacrylates 107
3.4.3 Polyethylene and Related Polymers 108
3.4.3.1 Hydrogel Polymers in this Group 110
3.4.4 Polyamides 111
3.4.5 Polyurethane and Polyurea 112
3.4.6 Polyesters 113
3.4.7 Polyethers 113
3.5 Natural Biopolymer 114
3.5.1 Collagen and Gelatins 114
3.5.2 Fibrin 115
3.5.3 Polysaccharide Hydrogels 115
3.5.4 Glycosaminoglycans 116
3.5.5 Alginates 117
3.5.6 Chitin and Chitosan 118
3.5.7 Dextran 119
3.6 Bioactive Polymers 120
3.6.1 Polymeric Drugs 121
3.6.1.1 Polycationic Polymers 121
3.6.1.2 Polyanionic Polymers 121
3.6.1.3 Polynucleotides/Polypeptides 121
3.6.1.4 Polysaccharides 121
3.6.2 Polymeric Drug Conjugates/Polymeric Protein Conjugates 122
3.6.3 Polymeric Prodrugs 123
3.6.4 Targeted Polymeric Drug 123
3.7 Biodegradable Polymers 123
3.7.1 Polyesters 124
3.7.2 Poly(ortho esters) 126
3.7.3 Polycarbonates 127
3.7.4 Polyanhydrides 127
3.7.5 Poly(phosphate ester) 128
3.7.6 Poly(phosphazenes) 128
3.8 Characterization of Biomaterials 129
3.8.1 Chemical Properties on the Surfaces 130
3.8.2 Physical Properties of the Surfaces 131
3.8.3 Adsorbed and Immobilized Protein Determination 132
3.8.4 In Vitro Cell Growth 132
3.8.5 Blood Compatibility 132
3.9 Fabrication Technology 133
3.9.1 Extrusion 133
3.9.2 Injection Molding 135
3.10 Future Trends in Biomedical Uses of Biopolymers 135
References 135
Part II The Interaction Between Materials and Living Tissues 138
4 Biomaterials: Processing, Characterization, and Applications 139
4.1 Introduction 139
4.2 Bone Biomechanics 139
4.2.1 Bone Composition and Structure 139
4.2.1.1 Composition 139
4.2.1.2 Bone Structure 140
4.2.1.3 Bone Physical Properties 141
4.2.2 Biomechanical Properties of Bone 142
4.2.2.1 Cortical Bone 142
4.2.2.2 Trabecular Bone 144
4.2.3 Bone Remodeling 145
4.3 Cartilage Biomechanics 146
4.3.1 Cartilage Composition and Structure 146
4.3.1.1 Structure 146
4.3.1.2 Composition 148
4.3.2 Biomechanical Properties of Cartilage 149
4.3.2.1 Permeability 149
4.3.2.2 Viscoelastic Properties 150
4.3.2.3 Cartilage Swelling 151
4.3.3 Cartilage Degeneration 151
4.4 Skin Biomechanics 152
4.4.1 Skin Composition and Structure 152
4.4.2 Biomechanical Properties of Skin 153
4.5 Tendon and Ligament Biomechanics 154
4.5.1 Structure and Composition 154
4.5.2 Biomechanical Properties of Tendons and Ligaments 155
4.6 Muscle Biomechanics 156
4.6.1 Muscle Structure and Composition 156
4.6.2 Biomechanical Properties of Muscles 158
4.7 Blood Vessel and Arterial Biomechanics 159
4.7.1 Composition and Structure of Blood Vessels and Arteries 159
4.7.2 Biomechanical Properties 161
4.7.3 Critical Closing Pressure 162
4.8 Joint Biomechanics 162
4.8.1 Description of Joint Biomechanics 163
4.8.2 Function of Joint Biomechanics 163
4.8.3 Mechanical Stresses of Joints 164
4.9 Conclusion 164
Bibliography 164
Bibliography 165
5 Metal Corrosion 171
5.1 Interaction of Metallic Biomaterials with the Human Body Environment 171
5.2 Electrochemical Reactions on Metallic Biomaterials 172
5.3 Forms of Corrosion of Metallic Biomaterials 185
5.3.1 Uniform Dissolution 186
5.3.2 Galvanic Corrosion 187
5.3.3 Concentration Cell Corrosion 189
5.3.4 Pitting and Crevice Corrosion 190
5.3.5 Environment Induced Cracking 192
5.3.6 Intergranular Corrosion 193
5.3.7 Wear-Corrosion, Abrasion-Corrosion, Erosion-Corrosion, Fretting 194
5.4 Corrosion Testing of Metallic Biomaterials 194
References 194
6 Wear 198
6.1 Introduction 198
6.2 Friction, Lubrication, and Wear 198
6.3 Wear Classifications and Fundamental Wear Mechanisms 200
6.3.1 Adhesive Wear 201
6.3.2 Fatigue Wear 202
6.3.3 Abrasive Wear and Third-Body Wear 203
6.3.4 Chemical (Corrosive) Wear 204
6.4 Wear in Biomedical Devices and Biomaterials 204
6.4.1 Wear in Prostheses and Biomedical Devices 205
6.4.2 Wear Resistance of Biomedical Materials 206
6.5 Summary 211
References 211
7 Inflammation, Carcinogenicity and Hypersensitivity 215
7.1 Introduction 215
7.2 Granulation Tissue 215
7.3 Foreign Body Response 216
7.4 Repair 217
7.5 Acute and Chronic Inflammation 218
7.6 Infection 220
7.7 Local and Systemic Responses 221
7.8 Soft and Hard Tissue Responses 221
7.9 BloodMaterial Interactions 223
7.10 Biocompatibility 224
7.11 Carcinogenicity 226
7.12 Hypersensitivity 227
References 227
8 Protein Interactions at Material Surfaces 229
8.1 Introduction 229
8.2 Protein Properties 229
8.2.1 Structure 230
8.2.1.1 Primary Structure 231
8.2.1.2 Secondary Structure 231
8.2.1.3 Tertiary Structure 234
8.2.1.4 Quaternary Structure 235
8.2.2 Isoelectric Point and Solubility 237
8.2.3 Hydrophobic Composition 237
8.3 Material Surface Properties 237
8.3.1 Surface Topography 238
8.3.2 Surface Energy 240
8.3.3 Surface Chemistry 241
8.4 Protein Adsorption on Surfaces 242
8.4.1 Kinetics and Thermodynamics 243
8.4.2 Density 244
8.4.3 Conformation 244
8.4.4 Extracellular Matrix Proteins 245
8.4.5 Cell Adhesive Amino Acid Sequences 246
8.5 Nanoscale Biomaterials 247
8.6 Conclusions 249
References 249
9 Sterility and Infection 252
9.1 Sterilization 252
9.1.1 Steam Autoclaves 252
9.1.2 Dry Heat 254
9.1.3 Radiation 254
9.1.4 Ethylene Oxide 254
9.1.5 New Technologies 255
9.2 Biomaterials Associated Infections 255
9.2.1 Biofilms 255
9.2.2 Types of Medical Related Biofilms 257
9.2.3 Infections Associated with Implantable Devices 258
9.2.3.1 Central Venus Catheters 258
9.2.3.2 Urinary Catheters 259
9.2.3.3 Prosthetic Heart Valves 259
9.2.3.4 Orthopedic Prosthetic Infections 259
9.3 The Use of Antibiotics in the Treatment of Biomaterials Associated Infections 261
9.3.1 Systemic Antibiotic Prophylaxis 261
9.3.2 Local Delivery of Antibiotics and Antimicrobial Agents 262
9.3.2.1 Antimicrobial Irrigation of a Surgical Field 262
9.3.2.2 Dipping of Biomaterials in Antimicrobial Solutions 262
9.3.2.3 The Antimicrobial Coating of Biomaterials 262
9.3.2.4 Placement of an Antimicrobial Carrier 262
9.4 Developing Infection-Preventing Biomaterials 263
9.5 Case Study: Oral Infections and Biomaterials 264
9.5.1 Dental Caries and Periapical Disease 265
9.5.2 Periodontal Disease 269
References 264
10 Biocompatibility Testing 274
10.1 Introduction 274
10.2 Sample Preparation 275
10.3 Mammalian Cell Culture 276
10.3.1 Cytotoxicity Testing 281
10.3.2 Hemocompatibility 288
10.3.3 Hypersensitivity/Allergic Responses 292
10.3.4 Genotoxicity 295
10.3.5 Tissue Specific Aspects of Biocompatibility Testing 299
10.4 Animal Experimentation 300
10.5 Alternatives to Animal Experimentation 301
References 301
Part III Applications of Polymers, Metals, and Ceramics in Medicine 306
11 Biomaterials for Dental Applications 307
11.1 Introduction 307
11.2 Historical Perspectives 308
11.3 Metals for Dental Application 308
11.3.1 Amalgams 308
11.3.2 Biocompatibility of Dental Amalgams 310
11.3.3 Casting Alloys 310
11.3.3.1 Titanium and Related Alloys 312
11.3.3.2 Casting and Soldering 314
11.3.4 Wrought Alloys as Orthodontic Wire 314
11.3.5 Dental Implants 316
11.3.5.1 Endosseous Implants 316
11.3.5.2 Subperiosteal Implants 317
11.3.5.3 Transosseous Implants 318
11.3.5.4 The Phenomenon of Osseointegration 318
11.3.5.5 Materials Issues in Dental Implants 319
11.3.5.6 Surface Issues 321
11.3.5.7 Problems with Dental Implants 324
11.4 Ceramics for Dental Applications 325
11.4.1 Metal-Ceramic Restorations 326
11.4.2 All-Ceramic Restorations 327
11.4.3 Processing of All-Ceramic Restorations 329
11.4.4 Selection Guide for All-Ceramic Restorations 330
11.4.5 Clinical Failure of All-Ceramic Crowns 331
11.4.6 Bioactive Glasses 331
11.5 Polymers for Dental Applications 331
11.5.1 Dentures 332
11.5.2 Dental Cements 332
11.5.3 Composite Dental Materials 334
11.6 Closure 335
References 335
12 Ophthalmic Biomaterials 339
12.1 Introduction 339
12.2 Oxygen Delivery 340
12.3 Refraction 342
12.4 Tissue Protection 344
12.5 Tissue Integration 345
12.5.1 Artificial Cornea Transplants 346
12.5.2 Artificial Eye 347
12.5.3 Retinal Implants 349
12.6 Modulation of Wound Healing 351
12.7 Interfacial Tension and Tamponade 352
12.8 Concluding Remarks 357
References 357
13 Hip Prosthesis 360
13.1 Introduction 360
13.2 History of Total Hip Replacement 362
13.3 Various Components and Design of THR 363
13.3.1 Socket or Acetabular Cup 364
13.3.2 The Ball 365
13.3.3 Stem 365
13.3.4 Fixation of THR 365
13.4 Various Materials for THR 367
13.4.1 Alumina 368
13.4.2 Yttria Stabilized Zirconia 369
13.4.3 Polyethylene 370
13.4.4 Cobalt Based Alloys 371
13.4.5 Titanium Based Alloys 373
13.4.6 Coatings 374
13.5 Design Variation of THR 376
References 376
14 Burn Dressing Biomaterials and Tissue Engineering 381
14.1 Introduction 381
14.2 Physiology of the Skin 381
14.2.1 Basic Organization and Cellular Composition 382
14.2.1.1 Keratinocytes 382
14.2.1.2 Melanocytes 383
14.2.1.3 Merkel Cells 383
14.2.1.4 Langerhans Cells 384
14.2.1.5 Fibroblasts 384
14.2.2 The Epidermis 384
14.2.2.1 Stratum Germinativum 385
14.2.2.2 Stratum Spinosum 385
14.2.2.3 Stratum Granulosum 386
14.2.2.4 Stratum Lucidum 386
14.2.2.5 Stratum Corneum 386
14.2.3 The Dermis 387
14.2.3.1 Papillary Dermis 388
14.2.3.2 Reticular Dermis 388
14.2.4 The Dermal-Epidermal Junction Zone 388
14.2.5 The Hypodermis 389
14.2.6 The Appendages 389
14.2.6.1 Sweat Glands 390
14.2.6.2 Sebaceous Glands 390
14.2.6.3 Hair Follicles 390
14.2.6.4 Nails 391
14.2.7 Functions of the Skin 391
14.3 Development of the Integumentary System 391
14.3.1 The Epidermis 392
14.3.2 The Dermis 392
14.3.3 The Appendages 393
14.4 Burns 393
14.4.1 Burn Classification 393
14.4.2 Principles of Burn Wound Healing 394
14.4.3 Immune System Response to Burn Injury 396
14.4.4 Complications 397
14.5 Conventional Treatment of Burns 397
14.5.1 Treatment of Minor Burns 397
14.5.2 Primary Treatment of Severe Burns 398
14.5.3 Autografting: The Current Gold Standard 399
14.5.4 Biological Alternatives for Temporary Wound Coverage 400
14.5.4.1 Allografts 400
14.5.4.2 Xenografts 401
14.6 Burn Dressing Biomaterials and Tissue Engineering 402
14.6.1 Design Criteria 402
14.6.1.1 Adherence 402
14.6.1.2 Barrier Properties 403
14.6.1.3 Mechanical Properties 403
14.6.1.4 Biodegradability and Immune Response 403
14.6.1.5 Surgical Handleability 403
14.6.1.6 Expense 404
14.6.2 Skin Substitutes 404
14.6.2.1 Epidermal Substitutes 404
14.6.2.2 Dermal Substitutes 409
14.6.2.3 Composite Substitutes 410
14.6.3 Growth Factor Incorporation 412
14.6.4 Epidermal Stem Cells 412
14.7 Future Outlook 412
References 412
15 Natural and Synthetic Polymeric Scaffolds 424
15.1 Introduction 424
15.2 Natural Polymers for Scaffold Fabrication 424
15.2.1 Polysaccharides 426
15.2.1.1 Agarose 426
15.2.1.2 Alginate 426
15.2.1.3 Hyaluronic Acid 427
15.2.1.4 Chitosan 427
15.3 Polypeptides 428
15.3.1 Collagen 428
15.3.1.1 Gelatin 429
15.3.1.2 Silk 429
15.4 Synthetic Polymers for Scaffold Fabrication 430
15.4.1 Polyesters 430
15.4.1.1 Poly(Glycolic Acid) 430
15.4.1.2 Poly(L-lactic acid) 432
15.4.1.3 Poly(D,L-lactic acid-co-glycolic acid) 433
15.4.1.4 Poly(-caprolactone) 433
15.4.1.5 Poly(propylene fumarate) 434
15.4.1.6 Polyorthoester 434
15.4.2 Other Synthetic Polymers 435
15.4.2.1 Polyanhydride 435
15.4.2.2 Polyphosphazene 435
15.4.2.3 Polycarbonate 436
15.4.2.4 Poly(ethylene glycol) 436
15.4.2.5 Polyurethane 437
15.5 Fabrication Techniques 437
15.5.1 Conventional Techniques 437
15.5.1.1 Fiber Bonding 437
15.5.1.2 Solvent-Casting Particulate-Leaching 438
15.5.1.3 Phase Separation 438
15.5.1.4 Melt Molding 438
15.5.1.5 Freeze Drying 439
15.5.1.6 Gas Foaming 439
15.5.2 Rapid Prototyping or Solid Freeform Fabrication Techniques 439
15.6 Properties for Scaffold Design 439
15.6.1 Polymer Assembly 440
15.6.2 Surface Properties 441
15.6.3 Macrostructure 441
15.6.4 Biocompatibility 442
15.6.5 Biodegradability 443
15.6.6 Mechanical Properties 444
15.7 Summary 444
References 444
16 BioMEMS 452
16.1 MEMS General Introduction 452
16.2 BioMEMS General Presentation 453
16.2.1 What Are They? 453
16.2.1.1 BioMEMS as Transducers 453
16.2.1.2 BioMEMS as Building Blocks for Micro Fluidic Elements 454
16.2.2 Why Building BioMEMS? 455
16.2.2.1 Favorable Exploitation of Miniaturization 455
16.2.2.2 Factual Possibility to Fabricate Such Small Systems 456
16.2.3 Risks and Drawback Associated to BioMEMS 457
16.2.3.1 In-Vitro BioMEMS Reliability 458
16.2.3.2 In-Vivo Reliability 458
16.3 BioMEMS Design, Materials and Fabrication 458
16.3.1 BioMEMS Design 458
16.3.2 BioMEMS: Importance of Materials and Materials Characterization 459
16.3.3 Material for BioMEMS 461
16.3.3.1 Silicon 461
16.3.3.2 Metals 462
16.3.3.3 Ceramics for MEMS Microfabrication 463
16.3.3.4 Polymers 464
16.3.3.5 Biomaterials and Nanomaterials 465
16.3.4 Biocompatibility of MEMS Materials 465
16.3.5 BioMEMS Fabrication Techniques 465
16.3.5.1 Photolithography 466
16.3.5.2 Bulk Micro-Machining 467
16.3.5.3 Surface Micro-Machining 470
16.3.5.4 Embosssing, Injection Molding Techniques 472
16.3.5.5 Stereophotolithography 472
16.3.5.6 Bonding, Hermetic Sealing and Packaging 473
16.3.5.7 From Top-Down to Bottom-Up 473
16.4 BioMEMS Application Review 474
16.4.1 BioMEMS Classification 474
16.4.2 BioMEMS for Cell Culturing 475
16.4.3 BioMEMS for DNA, Proteins and Chemical Analysis 476
16.4.4 BioMEMS for In-Vivo Applications: Interfacing with the Nervous System 478
16.4.5 Micro-Surgical Tools 479
16.5 Conclusion 480
References 480
17 Magnetic Particles for Biomedical Applications 485
17.1 Introduction 485
17.2 Magnetism and Magnetic Materials 486
17.2.1 Categories of Magnetic Materials 487
17.2.2 The Influence of Temperature 489
17.2.3 Magnetization Processes in Ferromagnetic and Ferrimagnetic Materials 489
17.2.4 Factors Affecting Magnetic Properties 490
17.3 Physical Principles 491
17.4 Examples and Property Requirements of Magnetic Biomaterials 493
17.5 Applications 493
17.5.1 Magnetic Separation 494
17.5.2 Drug Delivery 495
17.5.3 Radionuclide Delivery 496
17.5.4 Gene Delivery 496
17.5.5 Hyperthermia 496
17.5.6 Magnetic Resonance Imaging Contrast Agent 497
17.5.7 Artificial Muscle 498
17.6 Summary 498
References 498
18 Specialized Fabrication Processes: Rapid Prototyping 500
18.1 Introduction 500
18.2 Biomedical Applications of Rapid Prototyping-Tissue Engineering Scaffolds 501
18.3 Roles and Pre-Requisites for Tissue Engineering Scaffolds 501
18.4 Conventional Manual-Based Scaffold Fabrication Techniques 502
18.5 Computer-Controlled Freeform Fabrication Techniques for Tissue Engineering Scaffolds 503
18.5.1 Solid-Based Techniques 504
18.5.1.1 Fused Deposition Modeling (FDM) 504
18.5.1.2 ModelMaker II (MM II) 508
18.5.2 Powder-Based Techniques 509
18.5.2.1 Three-Dimensional Printing (3D-P) 509
18.5.2.2 Selective Laser Sintering (SLS) 510
18.5.3 Liquid-Based Techniques 512
18.5.3.1 Stereolithography Apparatus (SLA) 512
18.5.3.2 Rapid Freeze Prototyping (RFP) 514
18.6 Development of CAD Strategies and Solutions for Automated Scaffolds Fabrication 515
18.7 Prostheses 519
18.7.1 Integrated Approach to Prostheses Production 520
18.7.1.1 Data Acquisition 520
18.7.1.2 CAD Remodeling 521
18.7.1.3 Fabrication of Prosthesis Via RP 521
18.7.1.4 Casting of Actual Prosthesis 521
18.8 Case Studies 521
18.8.1 Case Study 1: Prosthetic Ear 522
18.8.2 Case Study 2: Prosthetic Forehead 523
18.9 Conclusion 525
References 525
19 Manufacturing Issues 531
19.1 Patents 532
19.1.1 EPC Contracting Countries 536
19.1.2 PCT Contracting Countries 536
19.1.3 Copyright 537
19.1.4 Trade Marks 538
19.1.5 Registered Design 538
19.1.6 Finally Litigation 539
19.2 Liability 540
19.3 Quality, Standards, Specifications 544
19.4 Audit 544
19.4.1 Design Dossier 545
19.5 FMEA 546
19.5.1 Standards 547
19.5.2 Specification 549
19.5.3 Manufacturing 549
Index 1