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8/17/14

Solution Manual for Biomaterials: The Intersection of Biology and Materials Science, 1st Edition, Johnna S. Temenoff, Antonios G. Mikos,

Solution Manual for Biomaterials The Intersection of Biology and Materials Science 1st Edition Johnna S. Temenoff Antonios G. Mikos

Solution Manual for Biomaterials The Intersection of Biology and Materials Science 1st Edition Johnna S. Temenoff Antonios G. Mikos .pdf

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

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

What is SM(Solution Manual)/IM (Instructor Manual/ISM(Instructor Solution Manual)?
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Step-Step Solutions of End of Chapter Questions/Problems in the text book
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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

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