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Biomaterials: The Intersection of Biology and Materials Science, CourseSmart eTextbook

By Johnna S. Temenoff, Antonios G. Mikos

Published by Prentice Hall

Published Date: Jan 8, 2008

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Description

Intended for use in an introductory course on biomaterials, taught primarily in departments of biomedical engineering. The book covers classes of materials commonly used in biomedical applications, followed by coverage of the biocompatibility of those materials with the biological environment. Finally, it covers some in-depth applications of biomaterials. It does all of this with an overall emphasis on tissue engineering.

Table of Contents

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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