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  Contents  
 
  Preface XVII
  Foreword XIX
  List of Contributors XXI
Part I Bone 1
1 Mineralization of Bone: An Active or Passive Process?
Thorsten Schinke and Michael Amling 		3
  Abstract 3
1.1 Physiological and Pathological Mineralization 3
1.2 Inhibitors of Pathological Mineralization 5
1.3 Activators of Physiological Mineralization 6
1.4 The Key Role of Pyrophosphate 9
1.5 The Mysterious Role of the Endopeptidase Phex 11
1.6 Concluding Remarks 13
References 14
2 Bone Morphogenetic Proteins
Walter Sebald, Joachim Nickel, Axel Seher, and Thomas D. Müller 		19
  Abstract 19
2.1 Introduction 19
2.2 What is a Bone Morphogenetic Protein? 21
2.3 BMP Receptors are Composed of Diverse Type I and Type II Receptor Chains 23
2.4 The Basic Signaling Mechanism is the Same for BMPs and other TGF- -like Proteins 24
2.5 Biochemistry and Cell Biology of Receptor Specificity 25
2.6 Structural Basis for Specificity and Affinity of BMP Receptor Interaction 27
2.7 What We Can Do with BMPs: The Engineering of BMP-2 and GDF-5 Variants 29
References 32
3 Biomechanics of Bones: Modeling and Computation of Bone Remodeling
Udo Nackenhorst 		35
  Abstract 35
3.1 Introduction 35
3.2 The Biomechanical Equilibrium Approach 36
3.3 A Computational Multi-Scale Approach for Cortical Bone 42
3.3.1 Closed Nano-to-Meso Control Circuit Approach 43
3.3.2 Sub-Cellular Length-Scale 44
3.3.3 Micro-Scale Model (Single Osteon) 45
3.3.4 Meso-Scale Model of Cortical Bone 45
3.4 Conclusions 46
References 47
4 Direct X-Ray Scattering Measurement of Internal Stresses and Strains in Loaded Bones
Stuart R. Stock and Jonathan D. Almer 		49
  Abstract 49
4.1 Introduction 49
4.2 Background 50
4.2.1 X-Ray Scattering 50
4.2.2 Strains and Stresses 51
4.3 Methods 51
4.3.1 Specimens and Geometry 51
4.3.2 Analysis of Two-Dimensional (2-D) Scattering Patterns 53
4.3.3 X-Ray Elastic Constants and Strain--Stress Conversion 55
4.4 Examples of Data and Analysis 55
4.5 Discussion and Future Directions 56
References 57
5 Osteoporosis and Osteopetrosis
Adele L. Boskey 		59
  Abstract 59
5.1 Introduction: Two Distinct Diseases with Common Features 59
5.1.1 Comparisons of Clinical Features of Osteoporosis and Osteopetrosis 60
5.1.1.1 Histology 60
5.1.1.2 Radiography 61
5.1.2 Comparisons of Bone Mineral Properties in Osteoporosis and Osteopetrosis 62
5.2 Animal Models of Osteoporosis and Osteopetrosis 63
5.2.1 Osteoporosis 63
5.2.1.1 Rodent Models 63
5.2.1.2 Non-Rodent Models 66
5.2.2 Osteopetrosis 66
5.2.2.1 Rodent Models 67
5.2.2.2 Other Osteopetrotic Models 68
5.3 The Cellular and Molecular Bases of Osteopetrosis and Osteoporosis 70
5.3.1 Osteoporosis 70
5.3.2 Osteopetrosis 72
5.4 Biomineralization in Osteopetrosis and Osteoporosis 74
References 75
6 Biomimetic Bone Substitution Materials
Matthias Epple 		81
  Abstract 81
6.1 The Clinical Need for Bone Substitution Materials 81
6.2 Synthetic Materials Used for Bone Substitution 82
6.3 Ceramics and Bone Cements 84
6.4 Polymers 86
6.4.1 PMMA-Based Materials 86
6.4.2 Polyester-Based Materials 86
6.5 Metals 87
6.6 Composites 87
6.7 Bone Substitutes of Biological Origin 87
6.8 Biological Functionalization of Synthetic Materials 90
6.9 An Example of a Synthetic Biomimetic Bone Substitution Material 90
6.10 Conclusions and Future Developments 91
References 92
7 Simulated Body Fluid (SBF) as a Standard Tool to Test the Bioactivity of Implants
Tadashi Kokubo and Hiroaki Takadama 		97
  Abstract 97
7.1 Introduction 97
7.2 Qualitative Correlation of Bone-Bonding Bioactivity of a Material with Apatite Formation on its Surface in SBF 98
7.3 Quantitative Correlation of Bone-Bonding Bioactivity and Apatite-Forming Ability in SBF 100
7.4 Ion Concentrations of SBF 101
7.5 Materials Able to Form Apatite 102
7.6 Composition and Structure of Apatite 103
7.7 Mechanism of Bonding of Bioactive Material to Bone 104
7.8 Mechanisms of Apatite Formation 105
7.9 Summary 106
References 106
8 Stimulation of Bone Growth on Implants by Integrin Ligands
Mónica López-García and Horst Kessler 		109
  Abstract 109
8.1 Introduction 109
8.1.1 Biomimetic Materials for Implant Technology 109
8.1.2 Integrins and RGD Sequence 110
8.1.3 Natural Proteins or Synthetic Peptides as Cell-Adhesive Molecules? 111
8.1.4 Integrin-Mediated Cell Adhesion 112
8.2 Improvements in Implant-Osseointegration by Surface Modification with Integrin Ligands 115
8.2.1 Mechanisms of Bone Grafting 115
8.2.2 Modifications on Implant Surfaces to Improve its Osseointegration 116
8.2.3 Structure of the Coating Molecules 117
8.2.4 Stimulation of Osteoblasts Adhesion and Proliferation on Implants Promoted by Integrin Ligands 118
8.2.4.1 Poly(methyl methacrylate) 118
8.2.4.2 Silks 120
8.2.4.3 Titanium 120
8.2.4.4 RGD Mimetics 121
8.3 Conclusions 123
References 123
9 Biochemical and Pathological Responses of Cells and Tissue to Micro- and Nanoparticles from Titanium and other Materials
Fumio Watari, Kazuchika Tamura, Atsruro Yokoyama, Kenichiro Shibata, Tsukasa Akasaka, Bunshi Fugetsu, Kiyotaka Asakura, Motohiro Uo, Yasunori Totsuka, Yoshinori Sato, and Kazuyuki Tohji 		127
  Abstract 127
9.1 Introduction 128
9.2 Materials and Methods 128
9.2.1 Specimens 128
9.2.2 Dissolution Testing of Ti Particles 129
9.2.3 Probe Cells 129
9.2.4 Biochemical Analyses of Cellular Reactions to Materials 129
9.2.5 Animal Experiments 129
9.3 Results 130
9.3.1 Dependence of Tissue Reaction In Vivo on Material Macroscopic Size 130
9.3.2 Effect of Particle Size on Biocompatibility 130
9.3.2.1 Size Distribution of the Abraded Particles 130
9.3.2.2 Particle Size Dependence In Vitro 131
9.3.2.3 Particle Size Dependence In Vivo 133
9.3.2.4 Material Dependence of the Particle Size Effect In Vitro 135
9.3.2.5 Material Dependency of Tissue Reaction to Particles In Vivo 135
9.3.3 Shape Effect 136
9.3.4 The Origin of the Particle Size Effect 137
9.3.5 Toxicity Level of Particle Size Effect for Bioactive and Bioinert Materials 138
9.3.6 Nanotoxicology 139
9.3.6.1 Size-Dependent Stimulus Down to Nanometer Size 139
9.3.6.2 Internal Diffusion of Nanoparticles 139
9.3.6.3 Toxicity-Enhancing Effects of Biostimulatory Materials by Nanosizing 140
9.4 Discussion 140
9.4.1 Particle Size-Dependence of Cytotoxicity 140
9.4.2 Particle Size-Dependence in Soft Tissues 141
9.4.3 Comparison of Ti, Fe, and Ni Particles 141
9.4.4 The Effect of Micro-/Nanosizing on Biological Reactions 142
9.4.5 Terminology on “Nanotoxicology” 143
References 143
10 Tissue Engineering of Bone
Hans-Peter Wiesmann, Beate Lüttenberg, and Ulrich Meyer 		145
  Abstract 145
10.1 Tissue Engineering: What Does it Mean? 145
10.2 Components of Bone Tissue Engineering 147
10.2.1 Osteoblasts 147
10.2.2 Bone Marrow Cells 148
10.2.3 Marrow-Derived Stem Cells 148
10.2.4 Vascular Cells 149
10.2.5 Scaffold Design and Cell Compatibility 149
10.2.6 Bioreactors 150
10.2.7 In-Vitro Cell Stimulation 150
10.2.7.1 Biophysical Stimulation 150
10.2.7.2 Biochemical Stimulation 151
10.3 Bone Biomineralization in Tissue Engineering Ex Vivo and In Vivo 151
10.3.1 Principles of ECM Biomineralization 151
10.3.2 Principles of Bone Formation 152
10.3.3 Particular Features of Extracorporeal Biomineralization 153
10.4 Clinical Demands 153
10.5 Future Aspects 154
References 155
Part II Teeth 157
11 Formation of Teeth
Katharina Reichenmiller and Christian Klein 		159
  Abstract 159
11.1 Introduction 159
11.2 Odontogenesis 163
11.2.1 Genes Involved in Odontogenesis 165
11.2.2 Stem Cells 165
11.3 Dentinogenesis 165
11.3.1 Mantle and Circumpulpal Dentin 166
11.3.2 Intertubular Dentin 168
11.3.3 Peritubular Dentin 168
11.4 Amelogenesis 170
11.5 Cementogenesis 172
11.5.1 Acellular Extrinsic Fiber Cementum (AEFC) 172
11.5.2 Cellular Intrinsic Fiber Cementum (CIFC) 173
11.5.3 Cellular Mixed Stratified Cementum (CMSC) 174
11.5.4 Acellular Intrinsic Fiber Cementum (AIFC) 174
11.6 Acknowledgments 174
References 174
12 The Structure of Teeth: Human Enamel Crystal Structure
Frédéric Cuisinier and Colin Robinson 		177
  Abstract 177
12.1 Introduction 177
12.2 HRTEM Observations 178
12.3 AFM Observations 179
12.4 Discussion 181
12.5 Conclusions 182
References 182
13 Design Strategies of Human Teeth: Biomechanical Adaptations
Paul Zaslansky and Steve Weiner 		183
  Abstract 183
13.1 Introduction 183
13.2 Deformation of Whole Teeth under Load 185
13.3 Mechanical Behavior of the Enamel Cap 191
13.4 The Role of Crown Dentin During Load Bearing 194
13.5 The Role of the Root and Supporting Structures 196
13.6 Broader Implications and Conclusions 198
References 200
14 Clinical Aspects of Tooth Diseases and their Treatment
Peter Gängler and Wolfgang H. Arnold 		203
  Abstract 203
14.1 Introduction 203
14.2 Tooth Development and Developmental Anomalies 206
14.2.1 Developmental Features and Elemental Analysis of Early Mineralization 207
14.2.2 Developmental Anomalies 210
14.3 Dental Caries 212
14.4 Periodontal Diseases 216
14.5 Dental Trauma 220
14.5.1 Acute Dental Trauma 220
14.5.2 Chronic Dental Trauma 220
References 221
15 Dental Caries: Quantifying Mineral Changes
Susan M. Higham and Philip W. Smith 		223
  Abstract 223
15.1 Introduction 223
15.2 Enamel Caries 224
15.3 Dentine Caries 224
15.4 Analyzing Mineral Changes in Dental Caries 225
15.4.1 Transverse Microradiography 226
15.4.2 TMR Studies 227
15.5 Quantitative Light-Induced Fluorescence 229
15.5.1 In Vitro QLF Studies 231
15.5.2 In Vivo QLF Studies 234
References 236
16 Periodontal Regeneration
Hom-Lay Wang and Lakshmi Boyapati 		239
  Abstract 239
16.1 Definitions 239
16.2 Periodontal Wound Healing 240
16.2.1 Wound-Healing Principles 240
16.2.2 Compartmentalization 241
16.2.3 Evaluating Regeneration 241
16.3 Techniques Used for Regeneration 241
16.3.1 Root Surface Biomodification 241
16.3.1.1 Root Surface Conditioning 241
16.3.2 Bone Replacement Grafts 242
16.3.2.1 Autografts 243
16.3.2.2 Allografts 243
16.3.2.3 Xenografts 245
16.3.2.4 Alloplasts 245
16.3.3 Guided Tissue Regeneration 246
16.3.3.1 Non-Absorbable Membranes 246
16.3.3.2 Absorbable Membranes 246
16.3.4 Biologic Modifiers 248
16.3.4.1 Growth Factors/Cytokines 248
16.3.4.2 Bone Morphogenetic Proteins (BMPs) 248
16.3.4.3 Pep-Gen p-15 249
16.3.4.4 Enamel Matrix Derivative (EMD) 249
16.4 Factors Influencing GTR Success 249
16.4.1 Patient Factors 251
16.4.2 Defect/Local Factors 251
16.4.3 Treatment Factors 252
16.4.4 Postoperative Care 252
16.5 Surgical Principles 253
16.5.1 Furcation Defects 253
16.5.2 Intrabony Defects 253
16.5.3 Root Coverage 253
16.5.4 Surgical Techniques 255
16.6 Conclusions 258
References 258
17 Tissue Engineering of Teeth
Misako Nakashima 		265
  Abstract 265
17.1 Introduction 265
17.2 The Triad 266
17.2.1 Pulp Stem/Progenitor Cells 266
17.2.1.1 Isolation 266
17.2.1.2 Self-Renewal 268
17.2.1.3 Multipotential Differentiation 269
17.2.2 Morphogenetic Signals, BMPs 269
17.2.3 Scaffold 270
17.3 Dentin Regeneration 271
17.3.1 Protein Therapy 271
17.3.2 Gene Therapy 272
17.3.2.1 In-Vivo BMP Gene Therapy 272
17.3.2.2 Ex-Vivo BMP Cell Therapy and Gene Therapy 273
17.4 Pulp Regeneration 276
17.4.1 Vasculogenesis 276
17.4.2 Neurogenesis 276
17.5 Whole-Teeth Regeneration 277
17.6 Conclusions and Future Perspectives 278
References 278
Part III Pathological Calcifications 283
18 Aspects of Pathological Calcifications
Inge Schmitz 		285
  Abstract 285
18.1 Introduction 285
18.1.1 Examples of Pathological Calcification 286
18.1.2 Regulation of Calcifications 287
18.2 Heterotopic Ossification 288
18.2.1 Calcification in Ulcera of Patients with Paraplegia 288
18.2.2 Calcifications of the Lung 289
18.2.2.1 Metastatic Pulmonary Calcifications 291
18.3 Vascular Calcifications: Arteriosclerosis 291
18.3.1 Calcifications of Arteries 291
18.3.1.1 Calcification of the Tunica Media (Mönckeberg's Arteriosclerosis) 292
18.3.1.2 Calcification of the Tunica Intima (Arteriosclerosis) 293
18.3.2 Ossifications of Arteries 294
18.3.3 Characterization of Atherosclerotic Plaques of the Human Aorta 294
18.4 Calcification of Synthetic Vascular Grafts 296
18.4.1 Chronic Kidney Disease-Dialysis and Vascular Calcification of Arteries and Arteriovenous Shunts 296
18.4.2 Ossification of Synthetic Grafts 298
18.5 Conclusions 299
References 299
19 Atherosclerosis: Cellular Aspects
Diane Proudfoot and Catherine M. Shanahan 		301
  Abstract 301
19.1 Introduction 301
19.2 Role of VSMCs in Vascular Calcification 303
19.2.1 Release of Apoptotic Bodies and Vesicles 303
19.2.2 Phagocytosis 305
19.2.3 VSMC Osteo/Chondrocytic Conversion 306
19.2.4 Role of Calcifying Vascular Cells and Pericytes 309
19.3 Role of Inflammatory Cells 310
19.3.1 Macrophages 310
19.3.2 Dendritic Cells, Mast Cells and T Lymphocytes 312
19.4 The Role of Osteoclasts: Is there a Possibility for Calcification-Regression? 312
19.5 Conclusions 313
References 313
20 The Biological and Cellular Role of Fetuin Family Proteins in Biomineralization
Cora Schäfer and Willi Jahnen-Dechent 		317
  Abstract 317
20.1 Osteogenesis and Bone Mineralization versus Calcification 317
20.2 2-HS Glycoprotein/Fetuin-A is a Systemic Inhibitor of Ectopic Calcification 320
20.3 The Mechanism of Fetuin-A Inhibition of Calcification 322
20.4 The Fate of Calciprotein Particles 322
References 325
21 Stone Formation
Pierfrancesco Bassi 		329
  Abstract 329
21.1 Urinary Stones 329
21.1.1 Pathogenesis 330
21.1.1.1 Inhibitors of Stone Formation 331
21.1.2 Classification of Urinary Stones 333
21.1.2.1 Calcium Stones 333
21.1.2.2 Uric Acid Stones 336
21.1.2.3 Magnesium Ammonium Phosphate Stones, Struvite or Infection Stones 337
21.1.2.4 Cystine Stones 338
21.1.3 Risk Factors 338
21.1.3.1 Non-Genetic Factors 338
21.1.3.2 Genetic Factors 341
21.2 Other Urological Stones: Testicular Microlithiasis 343
21.3 Biliary and Gallbladder Stones 343
21.4 Miscellaneous Stones 344
21.4.1 Sialolithiasis 344
21.4.2 Dental Stones 344
21.4.3 Pancreatic Stones 345
21.4.4 Broncholithiasis and Pulmonary Alveolar Microlithiasis 345
References 346
22 Ectopic Mineralization: New Concepts in Etiology and Regulation
Cecilia M. Giachelli 		349
  Abstract 349
22.1 Introduction 349
22.2 Regulators of Ectopic Mineralization 350
22.2.1 Circulating Factors that Regulate Ectopic Mineralization 350
22.2.2 Ion Transporters and Homeostatic Enzymes that Regulate Ectopic Mineralization 352
22.2.2.1 Role of Sodium-Dependent Phosphate Co-Transporters in Ectopic Mineralization 353
22.2.3 Extracellular Matrix Molecules that Regulate Ectopic Mineralization 354
22.2.3.1 Role of Osteopontin in Ectopic Mineralization 355
22.2.4 Cell Signaling Pathways that Regulate Ectopic Mineralization 355
22.2.5 Roles of Cell Death and Bone Remodeling in Ectopic Mineralization 357
22.3 Conclusions and Implications for Therapeutic Control of Ectopic Mineralization 358
References 358
23 Pathological Calcification of Heart Valve Bioprostheses
Birgit Glasmacher and Martin Krings 		361
  Abstract 361
23.1 Introduction 361
23.2 In-Vitro Calcification Models 364
23.3 Heart Valve Bioprostheses 364
23.4 Calcification Hypotheses and Study Design 364
23.5 Calcification Imaging Methods 365
23.6 Calcification Patterns 367
23.7 Description of Findings 369
23.8 Conclusions and Future Research 370
References 371
24 The Biomaterials Network (Biomat.net) as a Major Internet Resource for Biomaterials, Tissue Engineering and Biomineralization
Pedro L. Granja, José Paulo Pereira, and Mário A. Barbosa 		373
  Abstract 373
24.1 The Internet as a Major Healthcare Resource 373
24.2 Impact of Biomaterials Science in Modern Society 375
24.3 Biomat.net as a Biomineralization Resource 376
24.4 The Biomaterials Network (Biomat.net) 383
24.4.1 An Overview 383
24.4.2 Objectives 384
24.4.3 Team 385
24.4.4 Functionalities 386
24.4.4.1 Site Map 387
24.4.4.2 Membership 387
24.4.4.3 Links Lists 387
24.4.4.4 Directory of Researchers 387
24.4.4.5 Jobs 388
24.4.4.6 Newsletter 388
24.4.4.7 Endorsement of Scientific Meetings 389
References 389
  Index 391

 
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