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Solution Manual for Biomaterials: The Intersection of Biology and Materials Science, 1st Edition, Johnna S. Temenoff, Antonios G. Mikos, ISBN-10: 0130097101, ISBN-13: 9780130097101

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Table Of Contents:

 

Chapter 1: Materials for Biomedical Applications 1-1

1.1. Introduction to biomaterials 1-2

1.1.1. Important definitions 1-2

1.1.2. History and current status of the field 1-4

1.1.3 Future directions 1-7

1.2. Biological response to biomaterials 1-8

1.3. Biomaterial product testing and FDA approval 1-10

1.4. Types of biomaterials 1-11

1.4.1. Metals 1-11

1.4.2. Ceramics 1-11

1.4.3. Polymers 1-12

1.4.4. Naturally-derived vs. synthetic polymers 1-13

1.5. Processing of biomaterials 1-15

1.6. Important properties of biomaterials 1-16

1.6.1. Degradative properties of biomaterials 1-16

1.6.2. Surface properties of biomaterials 1-17

1.6.3. Bulk properties of biomaterials 1-19

1.6.4. Characterization techniques 1-20

1.7. Principles of chemistry 1-21

1.7.1. Atomic structure 1-22

1.7.2. Atomic models 1-22

1.7.2.1. Bohr model 1-23

1.7.2.2. Wave-mechanical model 1-23

1.7.3. Atomic orbitals 1-24

1.7.3.1. Shapes of orbitals 1-24

1.7.3.2. Order of subshells and the Aufbau principle 1-24

1.7.4. Valence electrons and the periodic table 1-26

1.7.5. Ionic bonding 1-27

1.7.5.1. Bonding and force-distance curves 1-27

1.7.5.2. Characteristics of the ionic bond 1-28

1.7.6. Covalent bonding 1-29

1.7.6.1. Atomic orbitals and hybridization 1-30

1.7.6.2. Molecular orbitals 1-32

1.7.6.3. Mixed bonds 1-33

1.7.7. Metallic bonding 1-34

1.7.8. Secondary forces 1-34

1.8. Summary 1-35

1.9. Problems 1-37

1.10. Tables 1-39

1.11. Figures 1-44

1.12. References 1-70

1.13. Additional reading 1-72

Chapter 2: Chemical Structure of Biomaterials 2-1

2.1. Introduction: Bonding and the structure of biomaterials 2-2

2.2. Structure of Metals 2-2

2.2.1. Crystal Structures 2-2

2.2.1.1. Face-centered cubic structure 2-3

2.2.1.2. Body-centered cubic structure 2-5

2.2.2. Crystal systems 2-6

2.2.3. Defects in crystal structures 2-10

2.2.3.1. Point defects 2-10

2.2.3.2. Impurities 2-11

2.2.4. Solid state diffusion 2-14

2.2.4.1. Diffusion mechanisms 2-14

2.2.4.2. Modeling of diffusion 2-15

2.3. Structure of Ceramics 2-18

2.3.1. Crystal structures 2-19

2.3.1.1. AX crystal structures 2-20

2.3.1.2. AmXp crystal structures 2-20

2.3.1.3. Carbon-based materials 2-21

2.3.2. Defects in crystal structures 2-22

2.3.2.1. Point defects 2-22

2.3.2.2. Impurities 2-24

2.4. Structure of polymers 2-24

2.4.1. General structure 2-25

2.4.1.1. Repeat units 2-25

2.4.1.2. Molecular weight determination 2-26

2.4.1.3. Mer configuration 2-30

2.4.1.4. Polymer structure 2-32

2.4.2. Polymer synthesis 2-34

2.4.2.1. Addition polymerization 2-34

2.4.2.2. Condensation polymerization 2-36

2.4.2.3. Polymer production via genetic engineering 2-36

2.4.3. Copolymers 2-37

2.4.4. Methods of polymerization 2-39

2.4.5. Crystal structures and defects 2-41

2.4.5.1. Crystal structures 2-41

2.4.5.2. Point defects and impurities 2-41

2.5. Techniques: Introduction to material characterization 2-41

2.5.1. X-ray diffraction 2-43

2.5.1.1. Basic principles 2-43

2.5.1.2. Instrumentation 2-45

2.5.1.3. Information provided 2-46

2.5.2. Ultra-violet and visible light spectroscopy (UV-VIS) 2-46

2.5.2.1. Basic principles 2-46

2.5.2.2. Instrumentation 2-47

2.5.2.3. Information provided 2-48

2.5.3. Infra-red spectroscopy (IR) 2-50

2.5.3.1. Basic principles 2-50

2.5.3.2. Instrumentation 2-50

2.5.3.3. Information provided 2-51

2.5.4. Nuclear magnetic resonance spectroscopy (NMR) 2-52

2.5.4.1. Basic principles 2-52

2.5.4.2. Instrumentation 2-54

2.5.4.3. Information provided 2-55

2.5.5. Mass spectrometry 2-55

2.5.5.1. Basic principles 2-55

2.5.5.2. Instrumentation 2-56

2.5.5.3. Information provided 2-57

2.5.6. High-performance liquid chromatography (HPLC):

size-exclusion chromatography 2-57

2.5.6.1. Basic principles 2-58

2.5.6.2. Instrumentation 2-58

2.5.6.3. Information provided 2-60

2.6. Summary 2-62

2.7. Problems 2-64

2.8. Tables 2-69

2.9. Figures 2-79

2.10. References 2-148

2.11. Additional reading 2-149

Chapter 3: Physical Properties of Biomaterials 3-1

3.1. Introduction: From atomic groupings to bulk materials 3-2

3.2. Crystallinity and linear defects 3-2

3.2.1. Dislocations 3-3

3.2.1.1. Edge dislocations 3-3

3.2.1.2. Screw and mixed dislocations 3-4

3.2.1.3. Characteristics of dislocations 3-4

3.2.2. Deformation 3-6

3.3. Crystallinity and planar defects 3-8

3.3.1. External surface 3-8

3.3.2. Grain boundaries 3-9

3.4. Crystallinity and volume defects 3-12

3.5. Crystallinity and polymeric materials 3-13

3.5.1. Percent crystallinity 3-14

3.5.2. Chain folded model of crystallinity 3-16

3.5.3. Defects in polymer crystals 3-17

3.5.3.1. Linear defects 3-17

3.5.3.2. Planar and volume defects 3-18

3.6. Thermal transitions of crystalline and non-crystalline materials 3-18

3.6.1. Viscous flow 3-18

3.6.2. Thermal transitions 3-19

3.6.2.1. Metals and crystalline ceramics 3-19

3.6.2.2. Amorphous ceramics (glasses) 3-19

3.6.2.3. Polymers 3-20

3.7. Techniques: Introduction to Thermal Analysis 3-26

3.7.1. Differential Scanning Calorimetry 3-27

3.7.1.1. Basic principles 3-27

3.7.1.2. Instrumentation 3-27

3.7.1.3. Information provided 3-28

3.8. Summary 3-30

3.9. Problems 3-32

3.10. Tables 3-35

3.11. Figures 3-38

3.12. References 3-63

3.13. Additional reading 3-64

Chapter 4: Mechanical Properties of Biomaterials 4-1

4.1. Introduction: Modes of mechanical testing 4-3

4.2. Mechanical testing methods, results and calculations 4-3

4.2.1. Tensile and shear properties 4-4

4.2.1.1. Calculations for tensile and shear tests 4-4

4.2.1.2. Stress-strain curves and elastic deformation 4-5

4.2.1.3. Molecular causes of elastic deformation 4-8

4.2.1.4. Stress-strain curves and plastic deformation 4-8

4.2.1.5. Molecular causes of plastic deformation 4-16

4.2.1.5.1. Metals and crystalline ceramics 4-17

4.2.1.5.2. Amorphous polymers and ceramics (glasses) 4-18

4.2.2. Bending properties 4-24

4.2.3. Time-dependent properties 4-27

4.2.3.1. Creep 4-27

4.2.3.2. Molecular causes of creep 4-29

4.2.3.2.1. Metals 4-29

4.2.3.2.2. Ceramics 4-30

4.2.3.2.3. Polymers 4-30

4.2.3.3. Stress relaxation and its causes 4-31

4.2.3.4. Mathematical models of viscoelastic behavior 4-31

4.2.3.4.1. Maxwell model 4-33

4.2.3.4.2. Voigt model 4-34

4.2.4. Influence of porosity and degradation on mechanical properties 4-39

4.3. Fracture and failure 4-40

4.3.1. Ductile and brittle fracture 4-40

4.3.2. Polymer crazing 4-41

4.3.3. Stress concentrators 4-42

4.4. Fatigue and fatigue testing 4-43

4.4.1. Fatigue 4-43

4.4.2. Fatigue testing 4-44

4.4.3. Factors that affect fatigue life 4-45

4.5. Methods to improve mechanical properties 4-46

4.6. Techniques: Introduction to Mechanical Analysis 4-49

4.6.1. Mechanical Testing 4-49

4.6.1.1. Basic principles 4-49

4.6.1.2. Instrumentation 4-50

4.6.1.3. Information provided 4-51

4.7. Summary 4-51

4.8. Problems 4-54

4.9. Figures 4-58

4.10. References 4-101

4.11. Additional reading 4-101

Chapter 5: Biomaterial Degradation 5-1

5.1. Introduction: Degradation in the biological environment 5-2

5.2. Corrosion/degradation of metals and ceramics 5-3

5.2.1. Fundamentals of corrosion 5-3

5.2.1.1. Oxidation-reduction reactions 5-3

5.2.1.2. Half-cell potentials 5-5

5.2.1.3. Nernst equation 5-6

5.2.1.4. Galvanic corrosion 5-9

5.2.2. Pourbaix diagrams and passivation 5-9

5.2.3. Contribution of processing parameters 5-12

5.2.3.1. Crevice corrosion 5-12

5.2.3.2. Pitting corrosion 5-13

5.2.3.3. Intergranular corrosion 5-13

5.2.4. Contribution of the mechanical environment 5-13

5.2.4.1. Stress and galvanic corrosion 5-14

5.2.4.2. Stress corrosion cracking 5-14

5.2.4.3. Fatigue corrosion 5-14

5.2.4.4. Fretting corrosion 5-15

5.2.5. Contribution of the biological environment 5-15

5.2.6. Means of corrosion control 5-16

5.2.7. Ceramic degradation 5-17

5.3. Degradation of polymers 5-18

5.3.1. Primary means of polymer degradation 5-18

5.3.2. Chain scission by hydrolysis 5-19

5.3.3. Chain scission by oxidation 5-20

5.3.4. Other means of degradation 5-21

5.3.4.1. Environmental stress cracking 5-21

5.3.4.2. Enzyme-catalyzed degradation 5-22

5.3.5. Effect of porosity 5-22

5.4. Biodegradable materials 5-22

5.4.1. Biodegradable ceramics 5-24

5.4.1.1. Erosion mechanisms 5-24

5.4.1.2. Factors that influence degradation rate 5-24

5.4.2. Biodegradable polymers 5-25

5.4.2.1. Introduction and definitions 5-25

5.4.2.2. Degradation mechanisms 5-28

5.4.2.3. Factors the influence degradation rate 5-29

5.5. Techniques: Assays for extent of degradation 5-29

5.6. Summary 5-30

5.7. Problems 5-32

5.8. Tables 5-37

5.9. Figures 5-40

5.10. References 5-54

5.11. Additional reading 5-55

Chapter 6: Biomaterial Processing 6-1

6.1. Introduction: Importance of biomaterials processing 6-2

6.2. Processing to improve bulk properties 6-2

6.2.1. Metals 6-2

6.2.1.1. Alloying 6-3

6.2.1.2. Strain hardening 6-4

6.2.1.3. Grain size refinement 6-5

6.2.1.4. Annealing 6-6

6.2.1.5. Precipitation hardening 6-9

6.2.2. Ceramics 6-9

6.2.3. Polymers 6-9

6.3. Processing to form desired shapes 6-12

6.3.1. Metals 6-12

6.3.1.1. Forming 6-12

6.3.1.1.1. Forging 6-13

6.3.1.1.2. Rolling 6-13

6.3.1.1.3. Extrusion 6-13

6.3.1.1.4. Drawing 6-13

6.3.1.2. Casting 6-14

6.3.1.2.1. Sand casting 6-14

6.3.1.2.2. Investment casting 6-15

6.3.1.3. Powder processing 6-15

6.3.1.4. Rapid manufacturing 6-16

6.3.1.5. Welding 6-16

6.3.1.6. Machining 6-17

6.3.2. Ceramics 6-17

6.3.2.1. Glass forming techniques 6-17

6.3.2.2. Casting and firing 6-18

6.3.2.2.1. Casting 6-18

6.3.2.2.2. Firing 6-19

6.3.2.3. Powder processing 6-20

6.3.2.4. Rapid manufacturing 6-20

6.3.3. Polymers 6-21

6.3.3.1. Thermoplasts vs. thermosets 6-21

6.3.3.2. Forming 6-23

6.3.3.2.1. Extrusion 6-23

6.3.3.2.2. Fiber spinning 6-23

6.3.3.3. Casting 6-25

6.3.3.3.1. Compression molding 6-25

6.3.3.3.2. Injection molding 6-25

6.3.3.3.3. Blow molding 6-25

6.3.3.4. Rapid manufacturing 6-26

6.4. Processing to improve biocompatibility 6-26

6.4.1. Sterilization 6-27

6.4.1.1. Steam sterilization 6-28

6.4.1.2. Ethylene oxide sterilization 6-28

6.4.1.3. Radiation sterilization 6-29

6.4.2. Fixation of natural materials 6-30

6.5. Summary 6-30

6.6. Problems 6-32

6.7. Tables 6-34

6.8. Figures 6-35

6.9. References 6-54

6.10. Additional reading 6-55

Chapter 7: Surface Properties of Biomaterials 7-1

7.1. Introduction: Concepts in surface chemistry and biology 7-2

7.1.1. Protein adsorption and biocompatibility 7-2

7.1.2. Surface properties governing protein adsorption 7-3

7.2. Physicochemical surface modification techniques 7-6

7.2.1. Introduction to surface modification techniques 7-6

7.2.2. Physicochemical surface coatings 7-7

7.2.2.1. Covalent surface coatings 7-7

7.2.2.1.1. Plasma treatment 7-7

7.2.2.1.2. Chemical vapor deposition 7-10

7.2.2.1.3. Physical vapor deposition 7-10

7.2.2.1.4. Radiation grafting/photografting 7-11

7.2.2.1.5. Self-assembled monolayers 7-12

7.2.2.2. Non-covalent surface coatings 7-14

7.2.2.2.1. Solution coatings 7-14

7.2.2.2.2. Langmuir-Blodgett films 7-14

7.2.2.2.3. Surface-modifying additives 7-15

7.2.3. Physicochemical surface modification methods with no overcoat 7-16

7.2.3.1. Ion beam implantation 7-17

7.2.3.2. Plasma treatment 7-18

7.2.3.3. Conversion coatings 7-18

7.2.3.4. Bioactive glasses 7-18

7.2.4. Laser methods for surface modification 7-19

7.3. Biological surface modification techniques 7-20

7.3.1. Covalent biological coatings 7-20

7.3.2. Non-covalent biological coatings 7-23

7.3.3. Immobilized enzymes 7-24

7.4. Surface properties and degradation 7-25

7.5. Patterning techniques for surfaces 7-25

7.6. Techniques: Introduction to surface characterization 7-27

7.6.1. Contact angle analysis 7-27

7.6.1.1. Basic principles 7-27

7.6.1.2. Instrumentation 7-30

7.6.1.3. Information provided 7-30

7.6.2. Light microscopy 7-31

7.6.2.1. Basic principles 7-31

7.6.2.2. Instrumentation 7-31

7.6.2.3. Information provided 7-32

7.6.3. Electron spectroscopy for chemical analysis (ESCA) or

X-ray photoelectron spectroscopy (XPS) 7-33

7.6.3.1. Basic principles 7-33

7.6.3.2. Instrumentation 7-34

7.6.3.3. Information provided 7-35

7.6.4. Attenuated total internal reflectance Fourier transform

infra-red spectroscopy (ATR-FTIR) 7-35

7.6.4.1. Basic principles 7-35

7.6.4.2. Instrumentation 7-36

7.6.4.3. Information provided 7-37

7.6.5. Secondary ion mass spectrometry (SIMS) 7-37

7.6.5.1. Basic principles 7-37

7.6.5.2. Instrumentation 7-38

7.6.5.3. Information provided 7-38

7.6.5. Electron microscopy: Transmission electron microscopy (TEM)

and Scanning electron microscopy (SEM) 7-39

7.6.6.1. Basic principles 7-39

7.6.6.2. Instrumentation 7-40

7.6.6.3. Information provided 7-41

7.6.6. Scanning probe microscopies (SPM):

Atomic force microscopy (AFM) 7-42

7.6.7.1. Basic principles 7-42

7.6.7.2. Instrumentation 7-42

7.6.7.3. Information provided 7-44

7.7. Summary 7-46

7.8. Problems 7-48

7.9. Tables 7-53

7.10. Figures 7-58

7.11. References 7-107

7.12. Additional reading 7-109

Chapter 8: Protein Interactions with Biomaterials 8-1

8.1. Introduction: Thermodynamics of protein adsorption 8-2

8.1.1. Gibbs free energy and protein adsorption 8-2

8.1.2. System properties governing protein adsorption 8-5

8.2. Protein structure 8-7

8.2.1. Amino acid chemistry 8-7

8.2.2. Primary structure 8-8

8.2.3. Secondary structure 8-9

8.2.4. Tertiary structure 8-12

8.2.5. Quaternary structure 8-13

8.3. Protein transport and adsorption kinetics 8-15

8.3.1. Transport to the surface 8-15

8.3.2. Adsorption kinetics 8-17

8.4. Reversibility of protein adsorption 8-18

8.4.1. Reversible and irreversible binding 8-18

8.4.2. Desorption and exchange 8-19

8.5. Techniques: Assays for protein type and amount 8-22

8.5.1. High-performance liquid chromatography: affinity chromatography 8-23

8.5.1.1. Basic principles 8-23

8.5.1.2. Instrumentation 8-24

8.5.1.3. Information provided 8-25

8.5.2. Colorimetric assays 8-28

8.5.2.1. Basic principles and instrumentation 8-28

8.5.3. Fluorescent assays 8-29

8.5.3.1. Basic principles 8-29

8.5.3.2. Instrumentation 8-30

8.5.3.3. Information provided 8-30

8.5.4. Enzyme-linked immunosorbent assay (ELISA) 8-31

8.5.4.1. Basic principles and procedures 8-31

8.5.5. Western blotting 8-32

8.5.5.1. Basic principles and procedures 8-32

8.6. Summary 8-33

8.7. Problems 8-35

8.8. Tables 8-39

8.9. Figures 8-42

8.10. References 8-74

8.11. Additional reading 8-75

Chapter 9: Cell Interactions with Biomaterials 9-1

9.1. Introduction: Cell-surface interactions and cellular functions 9-2

9.2. Cellular structure 9-3

9.2.1. Cell membrane 9-3

9.2.2. Cytoskeleton 9-5

9.2.3. Mitochondria 9-6

9.2.4. Nucleus 9-7

9.2.4.1. Structure and function of the nucleus 9-7

9.2.4.2. Structure of DNA 9-7

9.2.4.3. Structure of RNA 9-8

9.2.5. Endoplasmic reticulum 9-9

9.2.6. Vesicles 9-10

9.2.7. Membrane receptors and cell contacts 9-11

9.2.7.1. Types of cell contacts 9-11

9.2.7.2. Types of membrane receptors and ligands 9-12

9.3. Extracellular environment 9-14

9.3.1. Collagen 9-14

9.3.2. Elastin 9-16

9.3.3. Proteoglycans 9-16

9.3.4. Glycoproteins 9-17

9.3.5. Other ECM components 9-19

9.3.6. Matrix remodeling 9-20

9.3.7. ECM molecules as biomaterials 9-21

9.4. Cell-environment interactions affect cellular functions 9-23

9.4.1. Cell survival 9-24

9.4.2. Cell proliferation 9-25

9.4.2.1. Cell cycle: Interphase 9-25

9.4.2.2. Cell cycle: Mitosis 9-26

9.4.3. Cell differentiation 9-27

9.4.4. Protein synthesis 9-28

9.4.4.1. Collagen synthesis: transcription 9-29

9.4.4.2. Collagen synthesis: translation and post-translational modification 9-30

9.5. Models of adhesion, spreading and migration 9-34

9.5.1. Basic adhesion models: DLVO theory 9-34

9.5.2. DLVO theory limitations and further models 9-36

9.5.3. Models of cell spreading and migration 9-37

9.5.3.1. Cell spreading 9-37

9.5.3.2. Cell migration 9-37

9.6. Techniques: Assays to determine effects of cell-material interactions 9-43

9.6.1. Cytotoxicity assays 9-43

9.6.1.1. Direct contact assay 9-44

9.6.1.2. Agar diffusion assay 9-45

9.6.1.3. Elution assay 9-46

9.6.2. Adhesion/spreading assays 9-47

9.6.3. Migration assays 9-48

9.6.4. DNA and RNA assays 9-49

9.6.4.1. Polymerase chain reaction (PCR) and Reverse-transcription

polymerase chain reaction (RT-PCR) 9-50

9.6.4.2. Southern and Northern blotting 9-51

9.6.5. Protein production assays: Immunostaining 9-52

9.7. Summary 9-53

9.8. Problems 9-57

9.9. Tables 9-61

9.10. Figures 9-62

9.11. References 9-113

9.12. Additional reading 9-115

Chapter 10: Biomaterial Implantation and Acute Inflammation 10-1

10.1. Introduction: Overview of innate and acquired immunity 10-2

10.1.1. Characteristics of leukocytes 10-3

10.1.1.1. Leukocyte types 10-3

10.1.1.2. Leukocyte formation 10-4

10.1.1.3. Life span of leukocytes 10-4

10.1.2. Sources of innate immunity 10-5

10.2. Clinical signs of inflammation and their causes 10-5

10.3. Role of tissue macrophages and neutrophils 10-6

10.3.1. Migration of neutrophils 10-7

10.3.2. Actions of neutrophils 10-8

10.3.2.1. Phagocytosis 10-8

10.3.2.2. Respiratory burst 10-9

10.3.2.3. Secretion of chemical mediators 10-9

10.4. Role of other granulocytes 10-11

10.4.1. Monocytes/macrophages 10-11

10.4.2. Actions of macrophages 10-11

10.4.2.1. Phagocytosis and biomaterials 10-11

10.4.2.2. Secretion of chemical mediators 10-13

10.4.2.3. Role as antigen presenting cells 10-14

10.4.3. Other granulocytes 10-15

10.5. Termination of acute inflammation 10-16

10.6. Techniques: In vitro assays for inflammatory response 10-17

10.6.1. Leukocyte assays 10-17

10.6.2. Other assays 10-19

10.7. Summary 10-20

10.8. Problems 10-22

10.9. Tables 10-24

10.10. Figures 10-27

10.11. References 10-34

10.12. Additional reading 10-34

Chapter 11: Wound Healing and the Presence of Biomaterials 11-1

11.1. Introduction: Formation of granulation tissue 11-2

11.2. Foreign body reaction 11-3

11.3. Fibrous encapsulation 11-4

11.4. Chronic inflammation 11-7

11.5. Four types of resolution 11-8

11.6. Repair vs. regeneration: wound healing in skin 11-9

11.6.1. Skin repair 11-9

11.6.2. Skin regeneration 11-11

11.7. Techniques: In vivo assays for inflammatory response 11-12

11.7.1. Considerations in development of animal models 11-14

11.7.1.1. Choice of animal 11-14

11.7.1.2. Choice of implant site 11-14

11.7.1.3. Length of study 11-14

11.7.1.4. Biomaterial considerations: dose and administration 11-15

11.7.1.5. Inclusion of proper controls 11-16

11.7.2. Methods of assessment 11-17

11.7.2.1. Histology/immunohistochemistry 11-17

11.7.2.2. Electron microscopy 11-17

11.7.2.3. Biochemical assays 11-18

11.7.2.4. Mechanical testing 11-19

11.8. Summary 11-20

11.9. Problems 11-22

11.10. Tables 11-25

11.11. Figures 11-28

11.12. References 11-36

11.13. Additional reading 11-37

Chapter 12: Immune Response to Biomaterials 12-1

12.1. Introduction: Overview of acquired immunity 12-2

12.2. Antigen presentation and lymphocyte maturation 12-4

12.2.1. Major histocompatibility complex (MHC) molecules 12-4

12.2.1.1. MHC Class I 12-4

12.2.1.2. MHC Class II 12-4

12.2.1.3. MHC molecule variation and tissue typing 12-5

12.2.1.4. Intracellular complexation with MHC molecules 12-6

12.2.2. Maturation of lymphocytes 12-7

12.2.3. Activation and formation of clonal populations 12-8

12.3. B cells and antibodies 12-8

12.3.1. Types of B cells 12-8

12.3.2. Characteristics of antibodies 12-9

12.3.2.1. Structure of antibodies 12-9

12.3.2.2. Classes of antibodies 12-9

12.3.2.3. Mechanisms of antibody action 12-10

12.4. T cells 12-12

12.4.1. Types of T cells 12-12

12.4.2. Helper T lymphocytes (Th) 12-12

12.4.3. Cytotoxic T lymphocytes (Tc) 12-13

12.5. The complement system 12-14

12.5.1. Classical pathway 12-14

12.5.2. Alternative pathway 12-15

12.5.3. Membrane attack complex 12-16

12.5.4. Regulation of the complement system 12-17

12.5.5. Effects of the complement system 12-18

12.6. Undesired immune responses to biomaterials 12-19

12.6.1. Innate vs. acquired responses to biomaterials 12-20

12.6.2. Hypersensitivity 12-20

12.6.2.1. Type I: IgE mediated 12-21

12.6.2.2. Type II: Antibody mediated 12-21

12.6.2.3. Type III: Immune complex mediated 12-22

12.6.2.4. Type IV: T cell mediated 12-22

12.6.2.5. Hypersensitivity and the classes of biomaterials 12-23

12.7. Techniques: Assays for immune response 12-25

12.7.1. In vitro assays 12-25

12.7.2. In vivo assays 12-27

12.8. Summary 12-28

12.9. Problems 12-32

12.10. Tables 12-34

12.11. Figures 12-35

12.12. References 12-51

12.13. Additional reading 12-51

Chapter 13: Biomaterials and Thrombosis 13-1

13.1. Introduction: Overview of hemostasis 13-2

13.2. Role of platelets 13-2

13.2.1. Platelet characteristics and functions 13-2

13.2.2. Platelet activation 13-3

13.2.2.1. Means of activation 13-3

13.2.2.2. Sequelae of activation 13-3

13.3. Coagulation cascade 13-5

13.3.1. Intrinsic pathway 13-5

13.3.2. Extrinsic pathway 13-6

13.3.3. Common pathway 13-7

13.4. Means of limiting clot formation 13-9

13.5. Role of endothelium 13-11

13.6. Tests for hemocompatibility 13-13

13.6.1. General testing concerns 13-13

13.6.2. In vitro assessment 13-14

13.6.3. In vivo assessment 13-16

13.7. Summary 13-18

13.8. Problems 13-20

13.9. Tables 13-25

13.10. Figures 13-27

13.11. References 13-32

13.12. Additional reading 13-33

Chapter 14: Infection, Tumorigenesis and Calcification of Biomaterials 14-1

14.1. Introduction: Overview of other potential problems with

biomaterials implantation 14-2

14.2. Infection 14-2

14.2.1. Common pathogens and categories of infection 14-3

14.2.2. Steps to infection 14-4

14.2.3. Characteristics of the bacterial surface, the

biomaterial surface and the media 14-5

14.2.3.1. Bacterial surface properties 14-5

14.2.3.1.1. Gram positive vs. gram negative bacteria 14-5

14.2.3.1.2. Cell capsule and biofilm 14-6

14.2.3.2. Biomaterial surface properties 14-7

14.2.3.3. Media properties 14-8

14.2.4. Bacterial adhesion involves both specific and

non-specific interactions 14-8

14.2.5. Summary of implant-associated infections 14-9

14.3. Techniques for infection experiments 14-10

14.3.1. Means to characterize bacterial surfaces 14-11

14.3.1.1. Surface hydrophobicity 14-11

14.3.1.2. Surface charge 14-12

14.3.2. In vitro and in vivo models of infection 14-14

14.3.2.1. In vitro bacterial adhesion 14-14

14.3.2.2. Ex vivo and in vivo infection models 14-15

14.4. Tumorigenesis 14-16

14.4.1. Definitions and steps of tumorigenesis 14-16

14.4.2. Chemical vs. foreign body carcinogenesis 14-18

14.4.3. Timeline for foreign body tumorigenesis 14-19

14.4.3.1. Foreign body tumorigenesis with large implants 14-19

14.4.3.2. Foreign body tumorigenesis with small fibers 14-20

14.4.4. Summary of biomaterials-related tumorigenesis 14-20

14.5. Techniques for tumorigenesis experiments 14-21

14.5.1. In vitro models 14-21

14.5.2. In vivo models 14-22

14.6. Pathologic calcification 14-23

14.6.1. Introduction to pathologic calcification 14-23

14.6.2. Mechanism of pathologic calcification 14-24

14.6.3. Summary and techniques to reduce pathologic calcification 14-26

14.7. Techniques for pathologic calcification experiments 14-26

14.7.1. In vitro models of calcification 14-27

14.7.2. In vivo models of calcification 14-27

14.7.3. Sample assessment 14-28

14.8. Summary 14-30

14.9. Problems 14-33

14.10. Figures 14-36

14.11. References 14-45

14.12. Additional reading 14-46

List of Abbreviations Appendix I-1

List of Symbols Appendix I-6

Index Index 1