Temenoff Biomaterials

7/23/2019 Temenoff Biomaterials

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Bioma te r i a l sThe Intersection of Biologyand Materials Science

J. S. TemenoffWa llace H. Coulter Department of Biom edical EngineeringGeorgia Tech and Em ory University, Atlanta, GA

A. G. MikosDepa rtments of Bioengineering and Chem ical and Biom olecular EngineeringRice University, Houston, TX

Upper Saddle River, New Jersey 07458

PEARSONPrenticeHall


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ContentsForeword xixPreface xxiAcknowledgments xii i1M aterials for Biomedical A pplication s 11.1 Intro du ction to Biom aterials 1

1.1.1 Imp ortan t Definit ions 11.1.2 Histo ry and Cu rren t Status of the Field 21.1.3 Futu re Direction s 5

1.2 Biological Respo nse to Biom aterials 71.3 Biom aterial Prod uct Testing and FDA Ap prova l 81.4 Types of Bio ma terials 8

1.4.1 Metals 91.4.2 Ceramics 91.4.3 Polymers 101.4.4 Na tura lly Derived vs. Synthetic Polym ers 11

1.5 Proce ssing of Biom aterials 121.6 Im po rtan t Prope rties of Biom aterials 12

1.6.1 Deg radative Prope rties of Biom aterials 121.6.2 Surface Pro pert ies of Biom aterials 131.6.3 Bulk Prop erties of Biom aterials 141.6.4 Charac terizat ion Techniques 14

1.7 Principles of Ch em istry 151.7.1 Atom ic Structure 151.7.2 Atom ic Mo dels 16

1.7.2.1 Bohr Mo del 161.7.2.2 Wave-M echanical Mo del 171.7.3 Atom ic Orb itals 171.7.3.1 Shap es of Subshells (Orb itals) 171.7.3.2 Order of Subshells and the Aufbau Principle 111.7.4 Valence Elec trons and the Period ic Table 19

1.7.5 Ionic Bonding 211.7.5.1 Bond ing and Force-Distance Curves 211.7.5.2 Cha racteristics of the Ionic Bond 221.7.6 Cov alent Bon ding 231.7.6.1 Atomic Orbitals and Hyb ridization 231.7.6.2 Molecu lar Orbitals 261.7.6.3 Mixed Bonds 261.7.7 Metallic Bon ding 271.7.8 Seconda ry Forces 28

Summary 28Problems 29References 30Add it ional Reading 31


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2*

Chemical Structure of Biomaterials 322.1 Introduction: Bonding and the Structure of Biomaterials 322.2 Structure of Metals 33

2.2.1 Crystal Structures 332.2.1.1 Face-Centered Cubic Structure 332.2.1.2 Body-Centered Cubic Structure 352.2.2 Crystal Systems 362.2.3 Defects in Crystal Structures 412.2.3.1 Point Defects 412.2.3.2 Impurities 422.2.4 Solid State Diffusion 432.2.4.1 Diffusion Mechanisms 432.2.4.2 Modeling of Diffusion 44

2.3 Structure of Ceramics 472.3.1 Crystal Structures 472.3.1.1 AX Crystal Structures 482.3.1.2 AmXp Crystal Structures 502.3.1.3 Carbon-Based Materials 512.3.2 Defects in Crystal Structures 522.3.2.1 Point Defects 522.3.2.2 Impurities 53

2.4 Structure of Polymers 542.4.1 General Structure 542.4.1.1 Repeat Units 542.4.1.2 Molecular Weight Determination 562.4.1.3 Mer Configuration 602.4.1.4 Polymer Structure 622.4.2 Polymer Synthesis 642.4.2.1 Addition Polymerization 642.4.2.2 Condensation Polymerization 652.4.2.3 Polymer Production Via Genetic Engineering 652.4.3 Copolymers 662.4.4 Methods of Polymerization 672.4.5 Crystal Structures and Defects 692.4.5.1 Crystal Structures 692.4.5.2 Point Defects and Impurities 69

2.5 Techniques: Introduction to Material Characterization 692.5.1 X-Ray Diffraction 712.5.1.1 Basic Principles 712.5.1.2 Instrumentation 732.5.1.3 Information Provided 752.5.2 Ultraviolet and Visible Light Spectroscopy (UV-VIS) 752.5.2.1 Basic Principles 752.5.2.2 Instrumentation 762.5.2.3 Information Provided 78


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2.5.3 Infrared Spectroscopy (IR) 792.5 .3.1 Basic Principles 792.5.3.2 Instrumen tation 802.5.3.3 Inform ation Provided 812.5.4 Nuc lear Magn etic Resonance Spectroscopy (NM R) 822.5 .4.1 Basic Principles 822.5.4.2 Instrum entation 862.5.4.3 Information Provided 882.5.5 M ass Spectrometry 882.5 .5.1 Basic Principles 882.5.5.2 Instrum entation 882.5.5.3 Inform ation Provided 902.5.6 High-Performan ce Liquid Chro ma tograp hy (HPLC ): Size-ExclusionChromatography 912.5 .6.1 Basic Principles 912.5.6.2 Instrum entation 922.5.6.3 Inform ation Provided 93

Summary 95Problems 96References 99Addit ional Reading 100

3Physical Prop erties of Biom aterials 1013.1 Introduction : From Atomic Groupings to Bulk Materials 1013.2 Cry stallinity and Linea r Defects 102

3.2.1 Disloca tions 1023.2.1.1 Edge Dislocation s 1023.2.1.2 Screw and Mix ed Dislocation s 1033.2.1.3 Chara cteristics of Dislocation s 1063.2.2 Deform ation 107

3.3 Crystallinity and Planar Defects 1093.3.1 E xterna l Surface 1093.3.2 Grain Boundaries 1103.4 Crystallinity and Volume Defects 1123.5 Crystallinity and Polymerie Ma terials 1133.5.1 P ercent Crystallinity 1133.5.2 Cha in-Fo lded M ode l of Crystallinity 115

3.5.3 Defects in Polymer Crystals 1173.5.3.1 Linear Defects 1173.5.3.2 Plana r and Volume Defects 1183.6 Th erm al Tran sitions of Crystalline and No n-C rystalline Ma terials 118

3.6 .1 ViscousFlow 1183.6.2 Therm al Transit ions 1193.6.2.1 Me tals and Crystalline Ceram ics 1193.6.2.2 Am orp ho us Ceramics (Glasses) 1193.6.2.3 Polyme rs 120


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VIII Contents

3.7 Techniques: Introduction to Thermal Analysis 1243.7.1 Differential Scanning Calorimetry 1243.7.1.1 Basic Principles 1243.7.1.2 Instrumentation 1253.7.1.3 Information Provided 127

Summary 128Problems 129References 131Additional Reading 132

Mechanical Properties of Biomaterials 1314.1 Introduction: Modes of Mechanical Testing 1314.2 Mechanical Testing Methods, Results and Calculations 132

4.2.1 Tensile and Shear Properties 1334.2.1.1 Calculations for Tensile and Shear Tests 1334.2.1.2 Stress-Strain Curves and Elastic Deformation 1354.2.1.3 Molecular Causes of Elastic Deformation 1374.2.1.4 Stress-Strain Curves and Plastic Deformation 1374.2.1.5 Molecular Causes of Plastic Deformation 1444.2.1.6 Causes of Plastic DeformationMetals and CrystallineCeramics 1444.2.1.7 Causes of Plastic DeformationAmorphous Polymersand Ceramics (Glasses) 1464.2.1.8 Causes of Plastic DeformationPolymers (General) 1474.2.1.9 Causes of Plastic DeformationSemi-Crystalline Polymersand Elastomers 148

4.2.2 Bending Properties 1514.2.3 Time-Dependent Properties 1534.2.3.1 Creep 1534.2.3.2 Molecular Causes of CreepMetals 1544.2.3.3 Molecular Causes of CreepCeramics 1554.2.3.4 Molecular Causes of CreepPolymers 1564.2.3.5 Stress Relaxation and its Causes 1564.2.3.6 Mathematical Models of Viscoelastic Behavior 1574.2.3.7 Viscoelastic BehaviorMaxwell Model 1584.2.3.8 Viscoelastic BehaviorVoigt Model 1594.2.4 Influence of Porosity and Degradation on MechanicalProperties 162

4.3 Fracture and Failure 1634.3.1 Ductile and Brittle Fracture 1634.3.2 Polymer Crazing 1644.3.3 Stress Concentrators 165

4.4 Fatigue and Fatigue Testing 1674.4.1 Fatigue 1674.4.2 Fatigue Testing 1674.4.3 Factors that Affect Fatigue Life 169

4.5 Methods to Improve Mechanical Properties 1694.6 Techniques: Introduction to Mechanical Analysis 171

4.6.1 Mechanical Testing 1714.6.1.1 Basic Principles 171


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4.6.1.2 Instrumentation 1714.6.1.3 Information Provided 172


5Biomaterial D egradat ion 1775.1 Introdu ction: Deg radation in the Biological Environm ent 1775.2 Corro sion/D egrada tion of Metals and Ceramics 178

5.2.1 Fund ame ntals of Corro sion 1785.2.1.1 Oxid ation-Red uction Reactions 1785.2.1.2 Half-Cell Potentials 1805.2.1.3 Nerns t Equat ion 1815.2.1.4 Galvanic Corrosion 1845.2.2 Pourb aix Diagram s and Passivation 1845.2.3 Con tribution of Processing Parameters 1855.2.3.1 Crevice Corrosion 1865.2.3.2 Pitting Corrosion 1875.2.3.3 Intergranular Corrosion 1875.2.4 Co ntributio n of the Mech anical Environm ent 1875.2.4.1 Stress and Galvan ic Co rrosio n 1885.2.4.2 Stress Corro sion Cracking 1885.2.4.3 Fatigue Corrosion 1885.2.4.4 Frett ing Corro sion 189

5.2.5 Co ntributio n of the Biological Environm ent 1895.2.6 Me ans of Corrosion Con trol 1895.2.7 Ceram ic Deg radation 190

5.3 De gradatio n of Polymers 1905.3.1 Primary Me ans of Polymer Deg radation 1905.3.2 Ch ain Scission by Hyd rolysis 1915.3.3 Ch ain Scission by Ox ida tion 1915.3.4 Oth er Me ans of Deg radation 194

5.3.4.1 Environm ental Stress Cracking 1945.3.4.2 Enzyme-Catalyzed Degrad ation 194

5.3.5 Effects of Por osity 1955.4 Biod egradab le M ateria ls 1955.4.1 Biodegradable Ceramics 195

5.4.1.1 Erosion Mech anisms 1965.4.1.2 Factors that Influence Deg radation Rate 196

5.4.2 Biodegradable Polymers 1965.4.2.1 Introduction to Biodegradable Polymers and

Definitions 1965.4.2.2 Degradat ion Mechanisms 1985.4.2.3 Factors that Influence Deg radation Rate 198


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X Contents5.5 Techn iques: Assays for Exten t of De grad ation 199


6Biom aterial Processing 20 56.1 Introduc tion: Impo rtance of Biomaterials Processing 2056.2 Processing to Imp rove Bulk Prope rties 20 5

6.2.1 Metals 2066.2.1.1 Alloying 2066.2.1.2 Strain Hard ening 20 76.2.1.3 Gra in Size Refinement 20 76.2.1.4 Annealing 2076.2.1.5 Precipitation Hard ening 2096.2.2 Ceramics 2096.2.3 Polymers 209

6.3 Processing to Form Desired Shapes 2106.4 Processing of M etals 210

6.4.1 Forming Opera t ions 2106.4.1.1 Forging Metals 21 16.4.1.2 Rolling Me tals 21 16.4.1.3 Extrusion of Metals 21 16.4.1.4 Drawing Meta ls 2116.4.2 Casting Metals 2126.4.2.1 Sand Casting of M etals 21 26.4.2.2 Investment Casting of Metals 2126.4.3 Pow der Processing of M etals 21 2

6.4.4 Rapid Man ufacturing of Metals 2146.4.5 W elding Me tals 21 46.4.6 Mach ining of Metals 214

6.5 Processing of Ceram ics 21 56.5.1 Glass Forming Techniques 2156.5.2 Casting and Firing of Ceram ics 216

6.5.2.1 Casting Ceramics 2166.5.2.2 Firing Ceram ics 21 66.5.3 Pow der Processing of Ceram ics 21 7

6.5.4 Rapid Man ufacturing of Ceramics 21 76.6 Processing of Polymers 21 8

6.6.1 Therm oplasts vs. Therm osets 2186.6.2 F orming Polymers 219

6.6.2.1 Extrusion of Polymers 2196.6.2.2 Fiber Spinning of Polyme rs 21 9

6.6.3 Casting Polymers 22 16.6.3.1 Com pression Mo lding of Polymers 2216.6.3.2 Injection Mo lding of Polym ers 22 16.6.3.3 Blow Mo lding of Polymers 221


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6.6.4 Rapid Ma nufacturing of Polymers 2226.7 Processing to Imp rove Biocom patibility 22 3

6.7.1 Sterilization 2236.7.1 .1 Steam Sterilization 2236.7.1.2 Ethylene Ox ide Sterilization 22 36.7.1.3 Rad iat ion Steril izat ion 224

6.7.2 Fixation of Na tura l Materials 224Summary 225Problems 226References 226Add it ional Reading 22 7

7Surface Prop erties of Biom aterials 22 87.1 Intro du ctio n: Con cepts in Surface Chem istry and Biology 228

7.1.1 Protein Adso rption and Biocompatibili ty 2297.1.2 Surface Propert ies Governing Protein Ad sorption 2297.2 Physicochem ical Surface Mo dification Techniques 23 17.2.1 Introdu ction to Surface Mod ification Techniques 2317.2.2 Physicochem ical Surface Co atings : Cov alent SurfaceCoat ings 231

7.2.2.1 Plasma Treatm ent 2327.2.2.2 Chemical Vapor Deposit ion 2347.2.2.3 Physical Vapor De position 23 57.2.2.4 Rad iat ion Graft ing/Photograft ing 2357.2.2.5 Self-Assembled M ono laye rs 23 67.2.3 Physicochem ical Surface Co atings : No n-C ova lent SurfaceCoatings 2387.2.3.1 Solution Coatings 238

7.2.3.2 Langmuir-Blodgett Films 2387.2.3.3 Surface-Modifying Additives 24 07.2.4 Physicochemical Surface Mod ification Metho ds with NoOvercoat 2417.2.4.1 Ion Beam Imp lantat ion 2417.2.4.2 Plasma Treatm ent 2427.2.4.3 Conversion Coatings 2427.2.4.4 Bioactive Glasses 24 27.2.5 Laser M eth od s for Surface Mo dification 24 37.3 Biological Surface Mo dification Techniques 24 37.3.1 Co valen t Biological Coa tings 2447.3.2 No n-C ovalen t Biological Coatings 2467.3.3 Imm obil ized Enzymes 2467.4 Surface Prop erties and De grad ation 24 77.5 Patte rning Tech niques for Surfaces 24 77.6 Techniques: Introdu ction to Surface Charac terizat ion 2497.6.1 Co ntact Angle Analysis 2497.6.1 .1 Basic Principles 24 97.6.1.2 Instrum entation 252

7.6.1.3 Inform ation Provided 253


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7.6.2 Light Microscopy 2537.6.2 .1 Basic Principles 25 37.6.2.2 Instrum entation 2537.6.2.3 Information Provided 2557.6.3 Electron Spectroscopy for Chem ical Analysis (ESCA) or X-rayPho toelectro n Spectroscopy (XPS) 25 67.6.3.1 Basic Principles 25 67.6.3.2 Instrum entation 25 77.6.3.3 Inform ation Provided 2587.6.4 Atte nua ted Total Internal Reflectance Fou rier Transfo rm InfraredSpectroscopy (ATR-FTIR) 2587.6.4 .1 Basic Principles 25 87.6.4.2 Instrum entation 2607.6.4.3 Information Provided 26 17.6.5 Seconda ry Ion M ass Spectrom etry (SIMS) 26 27.6.5 .1 Basic Principles 26 27.6.5.2 Instrum entation 2627.6.5.3 Information Provided 262

7.6.6 Electron Microscopy: Transmission Electron Microsco py (TEM)and Scanning Electron Microscop y (SEM) 2627.6.6 .1 Basic Principles 2627.6.6.2 Instrum entation 26 57.6.6.3 Information Provided 2687.6.7 Scanning Probe Microscopy (SPM): Atomic Force Microsco py(AFM) 2687.6.7 .1 Basic Principles 2687.6.7.2 Instrum entation 2687.6.7.3 Information Provided 269

Summary 272Problems 273References 276Addit ional Reading 27 7

8Protein Interactions w ith Biomaterials 27 98.1 Introduction : Therm odynam ics of Protein Adso rption 2798.1.1 Gibbs Free Energy and Protein Ad sorption 2808.1.2 System Propert ies Governing Protein Adso rption 28 18.2 Protein Structure 28 48.2.1 Am ino Acid Chemistry 28 48.2.2 Prim ary Structure 2868.2.3 Seconda ry Structure 28 78.2.4 Tertiary Structure 29 18.2.5 Qu aternary Structure 2928.3 Protein Tran sport and Adso rption Kinetics 2938.3.1 Tra nsp ort to the Surface 29 38.3.2 Ad sorp tion Kinetics 29 58.4 Reversibility of Protein Ad sorptio n 29 6

8.4.1 Reversible and Irreversible Binding 29 68.4.2 Desorption and Exchange 297


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Contents X8.5 Techn iques: Assays for Protein Type and Am oun t 30 18.5.1 High-Performance Liquid Ch rom atogra phy (HPLC):Affini ty Chr om atogra phy 301

8.5.1.1 Basic Principles 30 18.5.1.2 Instrumentation 3028.5.1.3 Information Provided 302

8.5.2 C olorim etric Assays 3068.5.2.1 Basic Principles and Instru me ntatio n 3068.5.3 F luorescent Assays 3078.5.3.1 Basic Principles 30 78.5.3.2 Ins t rumenta t ion 3078.5.3.3 Information Provided 308

8.5.4 Enzym e-linked Im m uno sorb ent Assay (ELISA) 3088.5.4.1 Basic Principles and Procedu res 3088.5.5 W estern Blotting 3098.5.5.1 Basic Principles and Procedu res 309


9Cell Interactions with Biomaterials 3149.1 Intro du ctio n: Cell-Surface Interactio ns and Cellular Func tions 3149.2 Cellular Structure 315

9.2.1 Cell M em bran e 3159.2.2 Cytoskeleton 31 79.2 .3 Mitochon dr ia 3189.2.4 Nucleus 3189.2.4.1 Structure and Function of the Nucleus 3189.2.4.2 Structure of DN A 3189.2.4.3 Structure of RN A 3219.2.5 Endop lasmic Reticulum 3239.2.6 Vesicles 32 39.2.7 M em bran e Receptors and Cell Contacts 3249.2.7 .1 Types of Cell Co ntacts 32 49.2.7.2 Types of Me mb rane Receptors and Ligands 3249.3 Extracellular Environ men t 32 79.3.1 Collagen 3279.3.2 Elastin 3289.3.3 Proteoglycans 328

9.3.4 Glycoproteins 3309.3 .5 Other EC M Com ponents 3329.3.6 Ma trix Rem odeling 3349.3.7 EC M Molecules as Biomaterials 3359.4 Ce ll-En viron m ent Interac tions tha t Affect Cellular Func tions 3369.4.1 Cell Survival 3369.4.2 Cell Proliferation 3369.4.2 .1 Cell Cycle: Interphase 3379.4.2.2 Cell Cycle: Mitosis 33 7


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xiv Contents9.4.3 Cell Differentiation 3399.4.4 Protein Synthesis 340

9.4.4.1 Collagen Synthesis: Tran scription 34 19.4.4.2 Collagen Synthesis: Translat ion and Post-Translat ionalModificat ion 342

9.5 Mod els of Adhesion, Spreading and Mig ration 3479.5.1 Basic Adhesion Mo dels: DLVO Theory 3479.5.2 DLVO Theory Limitat ions and Further Mo dels 3489.5.3 Mo dels of Cell Spreading and Mig ration 3499.5.3 .1 Cell Spreading 3499.5.3.2 Cell Mig ration 3499.6 Techniques: Assays to Determ ine Effects of Cell-Ma terial Interaction s 353

9.6.1 Cy totoxicity Assays 3549.6.1.1 Direct Con tact Assay 3549.6.1.2 Agar Diffusion Assay 3559.6.1.3 Elution Assay 35 59.6.2 Ad hesion/Sp reading Assays 3569.6.3 M igration Assays 357

9.6.4 DN A and RN A Assays 3589.6.4.1 Polymerase Chain Reaction (PCR) and Reverse-Transcript ion Polymerase Chain Reaction (RT-PCR) 3589.6.4.2 Southern and No rthe rn Blotting 360

9.6.5 Protein Produc tion Assays: Imm unostaining 361Summary 362Problems 364References 366Addit ional Reading 366

10Biom aterial Im plan tation and Acute Inflamm ation 36910.1 Introduc tion: Overview of Innate and Acquired Imm unity 369

10.1.1 Chara cteristics of Leukocytes 37110.1.1.1 Leukocy te Types 37110.1.1.2 Leukocyte Form ation 37110.1.1.3 Life Span of Leukocytes 371

10.1.2 Sources of Innate Imm unity 37 110.2 Clinical Signs of Inflam matio n and Their Causes 37210.3 Role of Tissue Ma crophag es and Neu trophils 373

10.3.1 Migration of Neu trophils 37310.3.2 Actions of Neu trophils 375

10.3.2.1 Phagocytosis 37510.3.2.2 Respiratory Burst 37510.3.2.3 Secretion of Chem ical M edia tors 375

10.4 Role of Oth er Leukocy tes 37610.4.1 Monocytes /Macrophages 37610.4.2 Actions of Ma crophag es 377

10.4.2.1 Phagocytosis and Biomaterials 37 710.4.2.2 Secretion of Chem ical M edia tors 37 710.4.2.3 Role as Antigen-Presen ting Cells 378

10.4.3 Othe r Granulocytes 378


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10.5 Term ination of Acute Inflammation 37910.6 Techniques: In Vitro Assays for Inflam ma tory Respo nse 380

10.6.1 Leuko cyte Assays 38010.6.2 Oth er Assays 382Summary 382Problems 383References 384Add it ional Reading 384

11W ound He aling and the Presence of Biomaterials 38511.1 Introdu ction: Form ation of Gra nulat ion Tissue 38511.2 Foreign Body Reaction 38711.3 Fibrous Encapsu lat ion 38811.4 Chron ic Inflammation 38911.5 Four Types of Reso lution 39011.6 Repair vs. Regeneration: Wo und Healing in Skin 39111.6.1 Skin Repair 391

11.6.2 Skin Regeneration 39211.7 Techniques: In Vivo Assays for Inflam ma tory Respo nse 393

11.7.1 Con siderat ions in Developm ent of Animal Mod els 39411.7.1.1 Choice of Anim al 39411.7.1.2 Choice of Im plant Site 39511.7.1.3 Length of Study 39511.7.1.4 Biomaterial Considerat ions: Dose andAdministrat ion 39611.7.1.5 Inclusion of Prope r Co ntrols 396

11.7.2 M etho ds of Assessment 39611.7.2.1 Histology/Immunohistochemistry 39711.7.2.2 Electron Microscopy 39711.7 .2.3 Biochemical Assays 39811.7.2.4 Mech anical Testing 398

Summary 399Problems 399References 401Addit ional Reading 398

12Immune Respo nse to Biomaterials 40 312.1 Introdu ction: Overview of Acquired Imm unity 40312.2 Antigen Presentat ion and Lymphocyte Maturation 404

12.2.1 Major Histocom patibil i ty Com plex (MH C) Molecules 40412.2.1.1 M HC Clas s I 40 412.2.1.2 M H C Class II 40512.2.1.3 M H C Molecule Variat ion and Tissue Typing 40512.2.1.4 In t race l lu lar Com plexat ion wi th M H C Molecules 407

12.2.2 M atur atio n of Lymphocytes 40812.2.3 Activation and Form ation of Clonal Populat ions 408


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Xvi Contents12.3 B Cells and Antibo dies 40 9

12.3.1 Types of B Cells 40 912.3.2 Cha racteristics of Antibo dies 41 0

12.3.2.1 Structure of An tibodies 41 012.3.2.2 Classes of Antibo dies 41 012.3.2.3 Mech anisms of Antibody Action 412

12.4 T Cells 41 212.4.1 Types of T Cells 41 212.4.2 Helper T Cells (Th) 41312.4.3 Cytotoxic T Cells (Tc) 413

12.5 The Com plemen t System 41412.5.1 Classical Pathw ay 41412.5.2 Alternative Pathw ay 41612.5.3 Mem brane At tack Complex 41612.5.4 Regulation of the Com plemen t System 41 712.5.5 Effects of the Com plem ent System 418

12.6 Undesired Imm une Responses to Biomaterials 41812.6.1 Inna te vs. Acquired Responses to Biom aterials 41 912.6.2 Hypersensitivity 419

12.6.2.1 Type I: IgE Me diated 41 912.6.2.2 Type II: Antibody Me diated 41912.6.2.3 Type III : Imm une Com plex Med iated 42012.6.2.4 Type IV: T Cell Me diated 42 012.6 .2 .5 Hypersensit ivi ty and the Classes ofBiomater ia ls 421

12.7 Techniques: Assays for Imm une Respon se 42 212.7.1 In Vitro Assays 42212.7.2 In Vivo Assays 423Summary 424Problems 426References 426Addit ional Reading 426

13Biomaterials and Th rom bos is 42 813.1 Introduction : Overview of Hem ostasis 42813.2 Role of Platelets 42 9

13.2.1 Platelet Charac teristics and Func tions 42 913.2.2 Platelet Activation 42913.2.2.1 Me ans of Activation 42 913.2.2.2 Sequelae of Activation 42 9

13.3 Coagu lation Cascade 43013.3.1 Intrinsic Pathway 43113.3.2 Extrinsic Pathw ay 43213.3.3 Comm on Pa thway 432

13.4 Mea ns of Limiting Clot Form ation 43413.5 Role of the Endothelium 43513.6 Tests for Hem ocom patibil i ty 436


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13.6.1 Gen eral Testing Con cerns 43613.6.2 In Vitro Assessment 43713.6.3 In Vivo Assessment 438Summary 439Problems 440References 442Addit ional Reading 442

14Infection, Tumorigenesis and Calcificationof Biom aterials 44 414.1 Introduction: Overview of Other Potential Problems

with Biomaterial Imp lantat ion 44414.2 Infection 44 5

14.2.1 Co mm on Pathogens and Categories of Infection 44514.2.2 Steps to Infection 44614.2.3 Characteristics of the Bacterial Surface, the Biomaterial Surface,and the Media 447

14.2.3.1 Bacterial Surface Properties: Gram-Positive vs.Gram -Negative Bacteria 44 714.2.3.2 Bacterial Surface Properties: Cell Capsule andBiofilm 44714.2.3.3 Biom aterial Surface Properties 44 914.2.3.4 Med ia Propert ies 450

14.2.4 Specific and Non-SpecificInteractio ns Involved in Bacterial Adh esion 45014.2.5 Sum mary of Implan t-Associated Infections 45 114.3 Techn iques for Infection Exp erime nts 45 214.3.1 Cha racterizing Bacterial Surfaces 45 2

14.3.1.1 Surface Hyd rophob ici ty 45214.3.1.2 Surface Charg e 45 3

14.3.2 In Vitro and In Vivo Mo dels of Infection 45 414.3.2.1 In Vitro Bacterial Adh esion 45414.3.2.2 Ex Vivo and In Vivo Infection Mo dels 45 4

14.4 Tum origenesis 45 514.4.1 Definitions and Steps of Tum origenesis 45 514.4.2 C hem ical vs. Foreign Body Carcinogen esis 45 514.4.3 Timeline for Foreign Body Tum origenesis 45 614.4.3.1 Foreign Body Tum origenesis with Large Imp lants 45 6

14.4.3.2 Foreign Body Tum origenesis with Small Fibers 45 614.4.4 Summ ary of Biomaterial-Related Tumorigenesis 45 7

14.5 Techniques for Tum origenesis Exp erimen ts 45 814.5.1 In Vitro Models 45814.5.2 In Vivo Models 458

14.6 Patholo gie Calcification 45 914.6.1 Introduction to Pathologie Calcification 45914.6.2 Me chan ism of Patholog ie Calcification 45 914.6.3 Summ ary and Techniques to Reduce Pathologie Calcif icat ion 46 0


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14.7 Techniques for Patholo gie Calcification Exp erime nts 46 014.7.1 In Vitro Mo dels of Calcification 46 014.7.2 In Vivo Mo dels of Calcification 46 114.7.3 Sample Assessment 46 1Summary 463Problems 465References 466Addit ional Reading 466

A p p e n d i x I : Lis t of Abbreviat ions and Symbols 4 6 8Index 471

Temenoff Biomaterials

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Transcript of Temenoff Biomaterials