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1 Materials for Biomedical Applications1

1.1 Introduction to Biomaterials1

1.1.1 Important Definitions1

1.1.2 History and Current Status of the Field2

1.1.3 Future Directions5

1.2 Biological Response to Biomaterials7

1.3 Biomaterial Product Testing and FDA Approval8

1.4 Types of Biomaterials8

1.4.1 Metals9

1.4.2 Ceramics9

1.4.3 Polymers10

1.4.4 Naturally Derived vs.Synthetic Polymers11

1.5 Processing of Biomaterials12

1.6 Important Properties of Biomaterials12

1.6.1 Degradative Properties of Biomaterials12

1.6.2 Surface Properties of Biomaterials13

1.6.3 Bulk Properties of Biomaterials14

1.6.4 Characterization Techniques14

1.7 Principles of Chemistry15

1.7.1 Atomic Structure15

1.7.2 Atomic Models16

1.7.2.1 Bohr Model16

1.7.2.2 Wave-Mechanical Model17

1.7.3 Atomic Orbitals17

1.7.3.1 Shapes of Subshells（Orbitals）17

1.7.3.2 Order of Subshells and the Aufbau Principle18

1.7.4 Valence Electrons and the Periodic Table19

1.7.5 Ionic Bonding21

1.7.5.1 Bonding and Force-Distance Curves21

1.7.5.2 Characteristics of the Ionic Bond22

1.7.6 Covalent Bonding23

1.7.6.1 Atomic Orbitals and Hybridization23

1.7.6.2 Molecular Orbitals26

1.7.6.3 Mixed Bonds26

1.7.7 Metallic Bonding27

1.7.8 Secondary Forces28

Summary28

Problems29

References30

Additional Reading31

2 Chemical Structure of Biomaterials32

2.1 Introduction：Bonding and the Structure of Biomaterials32

2.2 Structure of Metals33

2.2.1 Crystal Structures33

2.2.1.1 Face-Centered Cubic Structure33

2.2.1.2 Body-Centered Cubic Structure35

2.2.2 Crystal Systems36

2.2.3 Defects in Crystal Structures41

2.2.3.1 Point Defects41

2.2.3.2 Impurities42

2.2.4 Solid State Diffusion43

2.2.4.1 Diffusion Mechanisms43

2.2.4.2 Modeling of Diffusion44

2.3 Structure of Ceramics47

2.3.1 Crystal Structures47

2.3.1.1 AX Crystal Structures48

2.3.1.2 AmXp Crystal Structures50

2.3.1.3 Carbon-Based Materials51

2.3.2 Defects in Crystal Structures52

2.3.2.1 Point Defects52

2.3.2.2 Impurities53

2.4 Structure of Polymers54

2.4.1 General Structure54

2.4.1.1 Repeat Units54

2.4.1.2 Molecular Weight Determination56

2.4.1.3 Mer Configuration60

2.4.1.4 Polymer Structure62

2.4.2 Polymer Synthesis64

2.4.2.1 Addition Polymerization64

2.4.2.2 Condensation Polymerization65

2.4.2.3 Polymer Production Via Genetic Engineering65

2.4.3 Copolymers66

2.4.4 Methods of Polymerization67

2.4.5 Crystal Structures and Defects69

2.4.5.1 Crystal Structures69

2.4.5.2 Point Defects and Impurities69

2.5 Techniques：Introduction to Material Characterization69

2.5.1 X-Ray Diffraction71

2.5.1.1 Basic Principles71

2.5.1.2 Instrumentation73

2.5.1.3 Information Provided75

2.5.2 Ultraviolet and Visible Light Spectroscopy（UV-VIS）75

2.5.2.1 Basic Principles75

2.5.2.2 Instrumentation76

2.5.2.3 Information Provided78

2.5.3 Infrared Spectroscopy（IR）79

2.5.3.1 Basic Principles79

2.5.3.2 Instrumentation80

2.5.3.3 Information Provided81

2.5.4 Nuclear Magnetic Resonance Spectroscopy（NMR）82

2.5.4.1 Basic Principles82

2.5.4.2 Instrumentation86

2.5.4.3 Information Provided88

2.5.5 Mass Spectrometry88

2.5.5.1 Basic Principles88

2.5.5.2 Instrumentation88

2.5.5.3 Information Provided90

2.5.6 High-Performance Liquid Chromatography（HPLC）：Size-Exclusion Chromatography91

2.5.6.1 Basic Principles91

2.5.6.2 Instrumentation92

2.5.6.3 Information Provided93

Summary95

Problems96

References99

Additional Reading100

3 Physical Properties of Biomaterials101

3.1 Introduction：From Atomic Groupings to Bulk Materials101

3.2 Crystallinity and Linear Defects102

3.2.1 Dislocations102

3.2.1.1 Edge Dislocations102

3.2.1.2 Screw and Mixed Dislocations103

3.2.1.3 Characteristics of Dislocations105

3.2.2 Deformation106

3.3 Crystallinity and Planar Defects108

3.3.1 External Surface108

3.3.2 Grain Boundaries109

3.4 Crystallinity and Volume Defects111

3.5 Crystallinity and Polymeric Materials112

3.5.1 Percent Crystallinity112

3.5.2 Chain-Folded Model of Crystallinity114

3.5.3 Defects in Polymer Crystals116

3.5.3.1 Linear Defects116

3.5.3.2 Planar and Volume Defects117

3.6 Thermal Transitions of Crystalline and Non-Crystalline Materials117

3.6.1 Viscous Flow117

3.6.2 Thermal Transitions117

3.6.2.1 Metals and Crystalline Ceramics117

3.6.2.2 Amorphous Ceramics（Glasses）118

3.6.2.3 Polymers118

3.7 Techniques：Introduction to Thermal Analysis123

3.7.1 Differential Scanning Calorimetry123

3.7.1.1 Basic Principles123

3.7.1.2 Instrumentation123

3.7.1.3 Information Provided125

Summary127

Problems128

References129

Additional Reading130

4 Mechanical Properties of Biomaterials131

4.1 Introduction：Modes of Mechanical Testing131

4.2 Mechanical Testing Methods，Results and Calculations132

4.2.1 Tensile and Shear Properties133

4.2.1.1 Calculations for Tensile and Shear Tests133

4.2.1.2 Stress-Strain Curves and Elastic Deformation135

4.2.1.3 Molecular Causes of Elastic Deformation137

4.2.1.4 Stress-Strain Curves and Plastic Deformation137

4.2.1.5 Molecular Causes of Plastic Deformation144

4.2.1.6 Causes of Plastic Deformation—Metals and Crystalline Ceramics144

4.2.1.7 Causes of Plastic Deformation—Amorphous Polymers and Ceramics（Glasses）146

4.2.1.8 Causes of Plastic Deformation—Polymers（General）147

4.2.1.9 Causes of Plastic Deformation—Semi-Crystalline Polymers and Elastomers148

4.2.2 Bending Properties151

4.2.3 Time-Dependent Properties153

4.2.3.1 Creep153

4.2.3.2 Molecular Causes of Creep—Metals154

4.2.3.3 Molecular Causes of Creep—Ceramics155

4.2.3.4 Molecular Causes of Creep—Polymers156

4.2.3.5 Stress Relaxation and its Causes156

4.2.3.6 Mathematical Models of Viscoelastic Behavior157

4.2.3.7 Viscoelastic Behavior—Maxwell Model158

4.2.3.8 Viscoelastic Behavior—Voigt Model159

4.2.4 Influence of Porosity and Degradation on Mechanical Properties162

4.3 Fracture and Failure163

4.3.1 Ductile and Brittle Fracture163

4.3.2 Polymer Crazing164

4.3.3 Stress Concentrators165

4.4 Fatigue and Fatigue Testing167

4.4.1 Fatigue167

4.4.2 Fatigue Testing167

4.4.3 Factors that Affect Fatigue Life169

4.5 Methods to Improve Mechanical Properties169

4.6 Techniques：Introduction to Mechanical Analysis171

4.6.1 Mechanical Testing171

4.6.1.1 Basic Principles171

4.6.1.2 Instrumentation171

4.6.1.3 Information Provided172

Summary172

Problems174

References176

Additional Reading176

5 Biomaterial Degradation177

5.1 Introduction：Degradation in the Biological Environment177

5.2 Corrosion/Degradation of Metals and Ceramics178

5.2.1 Fundamentals of Corrosion178

5.2.1.1 Oxidation-Reduction Reactions178

5.2.1.2 Half-Cell Potentials180

5.2.1.3 Nernst Equation181

5.2.1.4 Galvanic Corrosion184

5.2.2 Pourbaix Diagrams and Passivation184

5.2.3 Contribution of Processing Parameters185

5.2.3.1 Crevice Corrosion186

5.2.3.2 Pitting Corrosion187

5.2.3.3 Intergranular Corrosion187

5.2.4 Contribution of the Mechanical Environment187

5.2.4.1 Stress and Galvanic Corrosion188

5.2.4.2 Stress Corrosion Cracking188

5.2.4.3 Fatigue Corrosion188

5.2.4.4 Fretting Corrosion189

5.2.5 Contribution of the Biological Environment189

5.2.6 Means of Corrosion Control189

5.2.7 Ceramic Degradation190

5.3 Degradation of Polymers190

5.3.1 Primary Means of Polymer Degradation190

5.3.2 Chain Scission by Hydrolysis191

5.3.3 Chain Scission by Oxidation191

5.3.4 Other Means of Degradation194

5.3.4.1 Environmental Stress Cracking194

5.3.4.2 Enzyme-Catalyzed Degradation194

5.3.5 Effects of Porosity195

5.4 Biodegradable Materials195

5.4.1 Biodegradable Ceramics195

5.4.1.1 Erosion Mechanisms196

5.4.1.2 Factors that Influence Degradation Rate196

5.4.2 Biodegradable Polymers196

5.4.2.1 Introduction to Biodegradable Polymers and Definitions196

5.4.2.2 Degradation Mechanisms198

5.4.2.3 Factors that Influence Degradation Rate198

5.5 Techniques：Assays for Extent of Degradation199

Summary200

Problems201

References203

Additional Reading204

6 Biomaterial Processing205

6.1 Introduction：Importance of Biomaterials Processing205

6.2 Processing to Improve Bulk Properties205

6.2.1 Metals206

6.2.1.1 Alloying206

6.2.1.2 Strain Hardening207

6.2.1.3 Grain Size Refinement207

6.2.1.4 Annealing207

6.2.1.5 Precipitation Hardening209

6.2.2 Ceramics209

6.2.3 Polymers209

6.3 Processing to Form Desired Shapes210

6.4 Processing of Metals210

6.4.1 Forming Operations210

6.4.1.1 Forging Metals211

6.4.1.2 Rolling Metals211

6.4.1.3 Extrusion of Metals211

6.4.1.4 Drawing Metals211

6.4.2 Casting Metals212

6.4.2.1 Sand Casting of Metals212

6.4.2.2 Investment Casting of Metals212

6.4.3 Powder Processing of Metals212

6.4.4 Rapid Manufacturing of Metals214

6.4.5 Welding Metals214

6.4.6 Machining of Metals214

6.5 Processing of Ceramics215

6.5.1 Glass Forming Techniques215

6.5.2 Casting and Firing of Ceramics216

6.5.2.1 Casting Ceramics216

6.5.2.2 Firing Ceramics216

6.5.3 Powder Processing of Ceramics217

6.5.4 Rapid Manufacturing of Ceramics217

6.6 Processing of Polymers218

6.6.1 Thermoplasts vs.Thermosets218

6.6.2 Forming Polymers219

6.6.2.1 Extrusion of Polymers219

6.6.2.2 Fiber Spinning of Polymers219

6.6.3 Casting Polymers221

6.6.3.1 Compression Molding of Polymers221

6.6.3.2 Injection Molding of Polymers221

6.6.3.3 Blow Molding of Polymers221

6.6.4 Rapid Manufacturing of Polymers222

6.7 Processing to Improve Biocompatibility223

6.7.1 Sterilization223

6.7.1.1 Steam Sterilization223

6.7.1.2 Ethylene Oxide Sterilization223

6.7.1.3 Radiation Sterilization224

6.7.2 Fixation of Natural Materials224

Summary225

Problems226

References226

Additional Reading227

7 Surface Properties of Biomaterials228

7.1 Introduction：Concepts in Surface Chemistry and Biology228

7.1.1 Protein Adsorption and Biocompatibility229

7.1.2 Surface Properties Governing Protein Adsorption229

7.2 Physicochemical Surface Modification Techniques231

7.2.1 Introduction to Surface Modification Techniques231

7.2.2 Physicochemical Surface Coatings：Covalent Surface Coatings231

7.2.2.1 Plasma Treatment232

7.2.2.2 Chemical Vapor Deposition234

7.2.2.3 Physical Vapor Deposition235

7.2.2.4 Radiation Grafting/Photografting235

7.2.2.5 Self-Assembled Monolayers236

7.2.3 Physicochemical Surface Coatings：Non-Covalent Surface Coatings238

7.2.3.1 Solution Coatings238

7.2.3.2 Langmuir-Blodgett Films238

7.2.3.3 Surface-Modifying Additives240

7.2.4 Physicochemical Surface Modification Methods with No Overcoat241

7.2.4.1 Ion Beam Implantation241

7.2.4.2 Plasma Treatment242

7.2.4.3 Conversion Coatings242

7.2.4.4 Bioactive Glasses242

7.2.5 Laser Methods for Surface Modification243

7.3 Biological Surface Modification Techniques243

7.3.1 Covalent Biological Coatings244

7.3.2 Non-Covalent Biological Coatings246

7.3.3 Immobilized Enzymes246

7.4 Surface Properties and Degradation247

7.5 Patterning Techniques for Surfaces247

7.6 Techniques：Introduction to Surface Characterization249

7.6.1 Contact Angle Analysis249

7.6.1.1 Basic Principles249

7.6.1.2 Instrumentation252

7.6.1.3 Information Provided253

7.6.2 Light Microscopy253

7.6.2.1 Basic Principles253

7.6.2.2 Instrumentation253

7.6.2.3 Information Provided255

7.6.3 Electron Spectroscopy for Chemical Analysis（ESCA）or X-ray Photoelectron Spectroscopy（XPS）256

7.6.3.1 Basic Principles256

7.6.3.2 Instrumentation257

7.6.3.3 Information Provided258

7.6.4 Attenuated Total Internal Reflectance Fourier Transform—Infrared Spectroscopy（ATR-FTIR）258

7.6.4.1 Basic Principles258

7.6.4.2 Instrumentation260

7.6.4.3 Information Provided261

7.6.5 Secondary Ion Mass Spectrometry（SIMS）262

7.6.5.1 Basic Principles262

7.6.5.2 Instrumentation262

7.6.5.3 Information Provided262

7.6.6 Electron Microscopy：Transmission Electron Microscopy（TEM）and Scanning Electron Microscopy（SEM）262

7.6.6.1 Basic Principles262

7.6.6.2 Instrumentation265

7.6.6.3 Information Provided268

7.6.7 Scanning Probe Microscopy（SPM）：Atomic Force Microscopy（AFM）268

7.6.7.1 Basic Principles268

7.6.7.2 Instrumentation268

7.6.7.3 Information Provided269

Summary272

Problems273

References276

Additional Reading277

8 Protein Interactions with Biomaterials279

8.1 Introduction：Thermodynamics of Protein Adsorption279

8.1.1 Gibbs Free Energy and Protein Adsorption280

8.1.2 System Properties Governing Protein Adsorption281

8.2 Protein Structure284

8.2.1 Amino Acid Chemistry284

8.2.2 Primary Structure286

8.2.3 Secondary Structure287

8.2.4 Tertiary Structure291

8.2.5 Quaternary Structure292

8.3 Protein Transport and Adsorption Kinetics293

8.3.1 Transport to the Surface293

8.3.2 Adsorption Kinetics295

8.4 Reversibility of Protein Adsorption296

8.4.1 Reversible and Irreversible Binding296

8.4.2 Desorption and Exchange297

8.5 Techniques：Assays for Protein Type and Amount301

8.5.1 High-Performance Liquid Chromatography（HPLC）：Affinity Chromatography301

8.5.1.1 Basic Principles301

8.5.1.2 Instrumentation302

8.5.1.3 Information Provided302

8.5.2 Colorimetric Assays306

8.5.2.1 Basic Principles and Instrumentation306

8.5.3 Fluorescent Assays307

8.5.3.1 Basic Principles307

8.5.3.2 Instrumentation307

8.5.3.3 Information Provided308

8.5.4 Enzyme-linked Immunosorbent Assay（ELISA）308

8.5.4.1 Basic Principles and Procedures308

8.5.5 Western Blotting309

8.5.5.1 Basic Principles and Procedures309

Summary310

Problems311

References312

Additional Reading313

9 Cell Interactions with Biomaterials314

9.1 Introduction：Cell-Surface Interactions and Cellular Functions314

9.2 Cellular Structure315

9.2.1 Cell Membrane315

9.2.2 Cytoskeleton317

9.2.3 Mitochondria318

9.2.4 Nucleus318

9.2.4.1 Structure and Function of the Nucleus318

9.2.4.2 Structure of DNA318

9.2.4.3 Structure of RNA321

9.2.5 Endoplasmic Reticulum323

9.2.6 Vesicles323

9.2.7 Membrane Receptors and Cell Contacts324

9.2.7.1 Types of Cell Contacts324

9.2.7.2 Types of Membrane Receptors and Ligands324

9.3 Extracellular Environment327

9.3.1 Collagen327

9.3.2 Elastin328

9.3.3 Proteoglycans328

9.3.4 Glycoproteins330

9.3.5 Other ECM Components332

9.3.6 Matrix Remodeling334

9.3.7 ECM Molecules as Biomaterials335

9.4 Cell-Environment Interactions that Affect Cellular Functions336

9.4.1 Cell Survival336

9.4.2 Cell Proliferation336

9.4.2.1 Cell Cycle：Interphase337

9.4.2.2 Cell Cycle：Mitosis337

9.4.3 Cell Differentiation339

9.4.4 Protein Synthesis340

9.4.4.1 Collagen Synthesis：Transcription341

9.4.4.2 Collagen Synthesis：Translation and Post-Translational Modification342

9.5 Models of Adhesion，Spreading and Migration347

9.5.1 Basic Adhesion Models：DLVO Theory347

9.5.2 DLVO Theory Limitations and Further Models348

9.5.3 Models of Cell Spreading and Migration349

9.5.3.1 Cell Spreading349

9.5.3.2 Cell Migration349

9.6 Techniques：Assays to Determine Effects of Cell-Material Interactions353

9.6.1 Cytotoxicity Assays354

9.6.1.1 Direct Contact Assay354

9.6.1.2 Agar Diffusion Assay355

9.6.1.3 Elution Assay355

9.6.2 Adhesion/Spreading Assays356

9.6.3 Migration Assays357

9.6.4 DNA and RNA Assays358

9.6.4.1 Polymerase Chain Reaction（PCR）and Reverse-Transcription Polymerase Chain Reaction（RT PCR）358

9.6.4.2 Southern and Northern Blotting360

9.6.5 Protein Production Assays：Immunostaining361

Summary362

Problems364

References366

Additional Reading366

10 Biomaterial Implantation and Acute Inflammation369

10.1 Introduction：Overview of Innate and Acquired Immunity369

10.1.1 Characteristics of Leukocytes371

10.1.1.1 Leukocyte Types371

10.1.1.2 Leukocyte Formation371

10.1.1.3 Life Span of Leukocytes371

10.1.2 Sources of Innate Immunity371

10.2 Clinical Signs of Inflammation and Their Causes372

10.3 Role of Tissue Macrophages and Neutrophils373

10.3.1 Migration of Neutrophils373

10.3.2 Actions of Neutrophils375

10.3.2.1 Phagocytosis375

10.3.2.2 Respiratory Burst375

10.3.2.3 Secretion of Chemical Mediators375

10.4 Role of Other Leukocytes376

10.4.1 Monocytes/Macrophages376

10.4.2 Actions of Macrophages377

10.4.2.1 Phagocytosis and Biomaterials377

10.4.2.2 Secretion of Chemical Mediators377

10.4.2.3 Role as Antigen-Presenting Cells378

10.4.3 Other Granulocytes378

10.5 Termination of Acute Inflammation379

10.6 Techniques：In Vitro Assays for Inflammatory Response380

10.6.1 Leukocyte Assays380

10.6.2 Other Assays382

Summary382

Problems383

References384

Additional Reading384

11 Wound Healing and the Presence of Biomaterials385

11.1 Introduction：Formation of Granulation Tissue385

11.2 Foreign Body Reaction387

11.3 Fibrous Encapsulation388

11.4 Chronic Inflammation389

11.5 Four Types of Resolution390

11.6 Repair vs.Regeneration：Wound Healing in Skin391

11.6.1 Skin Repair391

11.6.2 Skin Regeneration392

11.7 Techniques：In Vivo Assays for Inflammatory Response393

11.7.1 Considerations in Development of Animal Models394

11.7.1.1 Choice of Animal394

11.7.1.2 Choice of Implant Site395

11.7.1.3 Length of Study395

11.7.1.4 Biomaterial Considerations：Dose and Administration396

11.7.1.5 Inclusion of Proper Controls396

11.7.2 Methods of Assessment396

11.7.2.1 Histology/Immunohistochemistry397

11.7.2.2 Electron Microscopy397

11.7.2.3 Biochemical Assays398

11.7.2.4 Mechanical Testing398

Summary399

Problems399

References401

Additional Reading401

12 Immune Response to Biomaterials403

12.1 Introduction：Overview of Acquired Immunity403

12.2 Antigen Presentation and Lymphocyte Maturation404

12.2.1 Major Histocompatibility Complex（MHC）Molecules404

12.2.1.1 MHC Class Ⅰ404

12.2.1.2 MHC Class Ⅱ405

12.2.1.3 MHC Molecule Variation and Tissue Typing405

12.2.1.4 Intracellular Complexation with MHC Molecules407

12.2.2 Maturation of Lymphocytes408

12.2.3 Activation and Formation of Clonal Populations408

12.3 B Cells and Antibodies409

12.3.1 Types of B Cells409

12.3.2 Characteristics of Antibodies410

12.3.2.1 Structure of Antibodies410

12.3.2.2 Classes of Antibodies410

12.3.2.3 Mechanisms of Antibody Action412

12.4 T Cells412

12.4.1 Types of T Cells412

12.4.2 Helper T Cells（Th）413

12.4.3 Cytotoxic T Cells（Tc）413

12.5 The Complement System414

12.5.1 Classical Pathway414

12.5.2 Alternative Pathway416

12.5.3 Membrane Attack Complex416

12.5.4 Regulation of the Complement System417

12.5.5 Effects of the Complement System418

12.6 Undesired Immune Responses to Biomaterials418

12.6.1 Innate vs.Acquired Responses to Biomaterials419

12.6.2 Hypersensitivity419

12.6.2.1 Type Ⅰ：IgE Mediated419

12.6.2.2 Type Ⅱ：Antibody Mediated419

12.6.2.3 Type Ⅲ：Immune Complex Mediated420

12.6.2.4 Type Ⅳ：T Cell Mediated420

12.6.2.5 Hypersensitivity and the Classes of Biomaterials421

12.7 Techniques：Assays for Immune Response422

12.7.1 In Vitro Assays422

12.7.2 In Vivo Assays423

Summary424

Problems426

References426

Additional Reading426

13 Biomaterials and Thrombosis428

13.1 Introduction：Overview of Hemostasis428

13.2 Role of Platelets429

13.2.1 Platelet Characteristics and Functions429

13.2.2 Platelet Activation429

13.2.2.1 Means of Activation429

13.2.2.2 Sequelae of Activation429

13.3 Coagulation Cascade430

13.3.1 Intrinsic Pathway431

13.3.2 Extrinsic Pathway432

13.3.3 Common Pathway432

13.4 Means of Limiting Clot Formation434

13.5 Role of the Endothelium435

13.6 Tests for Hemocompatibility436

13.6.1 General Testing Concerns436

13.6.2 In Vitro Assessment437

13.6.3 In Vivo Assessment438

Summary439

Problems440

References442

Additional Reading442

14 Infection，Tumorigenesis and Calcification of Biomaterials444

14.1 Introduction：Overview of Other Potential Problems with Biomaterial Implantation444

14.2 Infection445

14.2.1 Common Pathogens and Categories of Infection445

14.2.2 Steps to Infection446

14.2.3 Characteristics of the Bacterial Surface，the Biomaterial Surface，and the Media447

14.2.3.1 Bacterial Surface Properties：Gram-Positive vs.Gram-Negative Bacteria447

14.2.3.2 Bacterial Surface Properties：Cell Capsule and Biofilm447

14.2.3.3 Biomaterial Surface Properties449

14.2.3.4 Media Properties450

14.2.4 Specific and Non-Specific Interactions Involved in Bacterial Adhesion450

14.2.5 Summary of Implant-Associated Infections451

14.3 Techniques for Infection Experiments452

14.3.1 Characterizing Bacterial Surfaces452

14.3.1.1 Surface Hydrophobicity452

14.3.1.2 Surface Charge453

14.3.2 In Vitro and In Vivo Models of Infection454

14.3.2.1 In Vitro Bacterial Adhesion454

14.3.2.2 Ex Vivo and In Vivo Infection Models454

14.4 Tumorigenesis455

14.4.1 Definitions and Steps of Tumorigenesis455

14.4.2 Chemical vs.Foreign Body Carcinogenesis455

14.4.3 Timeline for Foreign Body Tumorigenesis456

14.4.3.1 Foreign Body Tumorigenesis with Large Implants456

14.4.3.2 Foreign Body Tumorigenesis with Small Fibers456

14.4.4 Summary of Biomaterial-Related Tumorigenesis457

14.5 Techniques for Tumorigenesis Experiments458

14.5.1 In Vitro Models458

14.5.2 In Vivo Models458

14.6 Pathologic Calcification459

14.6.1 Introduction to Pathologic Calcification459

14.6.2 Mechanism of Pathologic Calcification459

14.6.3 Summary and Techniques to Reduce Pathologic Calcification460

14.7 Techniques for Pathologic Calcification Experiments460

14.7.1 In Vitro Models of Calcification460

14.7.2 In Vivo Models of Calcification461

14.7.3 Sample Assessment461

Summary463

Problems465

References466

Additional Reading466

Appendix Ⅰ：List of Abbreviations and Symbols468

Index471