Maria Vallet-Regi
Bio-Ceramics with Clinical Applications
Maria Vallet-Regi
Bio-Ceramics with Clinical Applications
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This publication offers a unique approach that links the materials science of bioceramics to clinical needs and applications.
Providing a structured account of this highly active area of research, the book reviews the clinical applications in bone tissue engineering, bone regeneration, joint replacement, drug-delivery systems and biomimetism, this book is an ideal resource for materials scientists and engineers, as well as for clinicians.
From the contents:
Part I Introduction
1. Bioceramics 2. Biomimetics
Part II Materials
3. Calcium Phosphate Bioceramics 4. Silica-based…mehr
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This publication offers a unique approach that links the materials science of bioceramics to clinical needs and applications.
Providing a structured account of this highly active area of research, the book reviews the clinical applications in bone tissue engineering, bone regeneration, joint replacement, drug-delivery systems and biomimetism, this book is an ideal resource for materials scientists and engineers, as well as for clinicians.
From the contents:
Part I Introduction
1. Bioceramics
2. Biomimetics
Part II Materials
3. Calcium Phosphate Bioceramics
4. Silica-based Ceramics: Glasses
5. Silica-based Ceramics: Mesoporous Silica
6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics
7. Carbon-based Materials in Biomedicine
Part III Material Shaping
8. Cements
9. Bioceramic Coatings for Medical Implants
10. Scaffold Designing
Part IV Research on Future Ceramics
11. Bone Biology and Regeneration
12. Ceramics for Drug Delivery
13. Ceramics for Gene Transfection
14. Ceramic Nanoparticles for Cancer Treatment
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Providing a structured account of this highly active area of research, the book reviews the clinical applications in bone tissue engineering, bone regeneration, joint replacement, drug-delivery systems and biomimetism, this book is an ideal resource for materials scientists and engineers, as well as for clinicians.
From the contents:
Part I Introduction
1. Bioceramics
2. Biomimetics
Part II Materials
3. Calcium Phosphate Bioceramics
4. Silica-based Ceramics: Glasses
5. Silica-based Ceramics: Mesoporous Silica
6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics
7. Carbon-based Materials in Biomedicine
Part III Material Shaping
8. Cements
9. Bioceramic Coatings for Medical Implants
10. Scaffold Designing
Part IV Research on Future Ceramics
11. Bone Biology and Regeneration
12. Ceramics for Drug Delivery
13. Ceramics for Gene Transfection
14. Ceramic Nanoparticles for Cancer Treatment
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Produktdetails
- Produktdetails
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 488
- Erscheinungstermin: 3. Juni 2014
- Englisch
- Abmessung: 246mm x 175mm x 28mm
- Gewicht: 907g
- ISBN-13: 9781118406755
- ISBN-10: 1118406753
- Artikelnr.: 40721583
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 488
- Erscheinungstermin: 3. Juni 2014
- Englisch
- Abmessung: 246mm x 175mm x 28mm
- Gewicht: 907g
- ISBN-13: 9781118406755
- ISBN-10: 1118406753
- Artikelnr.: 40721583
Maria Vallet-Regi is full Professor of Inorganic Chemistry and Head of the Department of Inorganic and Bioinorganic Chemistry of the Faculty of Pharmacy at Universidad Complutense de Madrid, Spain. Professor Vallet-Regí has written over 500 articles and more than 20 books. She is the most cited Spanish scientist in the field of Materials Science in this last decade, according to ISI Web of Knowledge. She has presented her research around the world at over 300 international conferences Professor Vallet-Regí has received many awards including: the French-Spanish award of the year 2000 from the Societé Française de Chimie; the Inorganic Chemistry award 2008 from the Spanish Royal Society of Chemistry; the 2008 Spanish National Research Award "Leonardo Torres Quevedo" in the field of Engineering and Spanish Royal Society of Chemistry (RSEQ) research award 2011 (RSEQ medal).
List of Contributors xiii
Preface xv
Part I Introduction 1
1. Bioceramics 3
María Vallet-Regí
1.1 Introduction 3
1.2 Reactivity of the Bioceramics 4
1.3 First, Second, and Third Generations of Bioceramics 6
1.4 Multidisciplinary Field 7
1.5 Solutions for Bone Repairing 8
1.6 Biomedical Engineering 13
Recommended Reading 15
2. Biomimetics 17
María Vallet-Regí
2.1 Biomimetics 17
2.2 Formation of Hard Tissues 18
2.3 Biominerals versus Biomaterials 19
Recommended Reading 22
Part II Materials 23
3. Calcium Phosphate Bioceramics 25
Daniel Arcos
3.1 History of Calcium Phosphate Biomaterials 25
3.2 Generalities of Calcium Phosphates 26
3.3 In vivo Response of Calcium Phosphate Bioceramics 28
3.4 Calcium Hydroxyapatite-Based Bioceramics 30
3.4.1 Stoichiometric Hydroxyapatite (HA) 31
3.4.2 Calcium Deficient Hydroxyapatites (CDHA) 37
3.4.3 Carbonated Hydroxyapatites (CHA) 39
3.4.4 Silicon-Substituted Hydroxyapatite (Si-HA) 40
3.4.5 Hydroxyapatites of Natural Origin 45
3.5 Tricalcium Phosphate-Based Bioceramics 50
3.5.1 -Tricalcium Phosphate (-TCP) 50
3.5.2 -Tricalcium Phosphate (-TCP) 53
3.6 Biphasic Calcium Phosphates (BCP) 55
3.6.1 Chemical and Structural Properties 55
3.6.2 Preparation Methods 56
3.6.3 Clinical Applications 56
3.7 Calcium Phosphate Nanoparticles 57
3.7.1 General Properties and Scope of Calcium Phosphate Nanoparticles 57
3.7.2 Preparation Methods of CaP Nanoparticles 58
3.7.3 Clinical Applications 60
3.8 Calcium Phosphate Advanced Biomaterials 60
3.8.1 Scaffolds for in situ Bone Regeneration and Tissue Engineering 60
3.8.2 Drug Delivery Systems 62
References 65
4. Silica-based Ceramics: Glasses 73
Antonio J. Salinas
4.1 Introduction 73
4.1.1 What Is a Glass? 73
4.1.2 Properties of Glasses 75
4.1.3 Structure of Glasses 75
4.1.4 Synthesis of Glasses 76
4.2 Glasses as Biomaterials 78
4.2.1 First Bioactive Glasses (BGs): Melt-Prepared Glasses (MPGs) 79
4.2.2 Other Bioactive MPGs 80
4.2.3 Bioactivity Index and Network Connectivity 80
4.2.4 Mechanism of Bioactivity 81
4.3 Increasing the Bioactivity of Glasses: New Methods of Synthesis 82
4.3.1 Sol-Gel Glasses (SGGs) 82
4.3.2 Composition, Texture, and Bioactivity of SSGs 84
4.3.3 Biocompatibility of SGGs 86
4.3.4 SGGs as Bioactivity Accelerators in Biphasic Materials 86
4.3.5 Template Glasses (TGs) Bioactive Glasses with Ordered Mesoporosity 88
4.3.6 Atomic Length Scale in BGs: How the Local Structure Affects
Bioactivity 91
4.3.7 New Reformulation of Hench's Mechanism for TGs 93
4.3.8 Including Therapeutic Inorganic Ions in the Glass Composition 94
4.4 Strengthening and Adding New Capabilities to Bioactive Glasses 95
4.4.1 Glass Ceramics (GCs) 95
4.4.2 Composites Containing Bioactive Glasses 97
4.4.3 Sol-Gel Organic-Inorganic Hybrids (O-IHs) 98
4.5 Non-silicate Glasses 99
4.5.1 Phosphate Glasses 99
4.5.2 Borate Glasses 100
4.6 Clinical Applications of Glasses 101
4.6.1 Bioactive Silica Glasses 101
4.6.2 Inert Silica Glasses 106
4.6.3 Phosphate Glasses 106
4.6.4 Borate Glasses 107
Recommended Reading 107
5. Silica-based Ceramics: Mesoporous Silica 109
Montserrat Colilla
5.1 Introduction 109
5.2 Discovery of Ordered Mesoporous Silicas 110
5.3 Synthesis of Ordered Mesoporous Silicas 111
5.3.1 Hydrothermal Synthesis 112
5.3.2 Evaporation-Induced Self-Assembly (EISA) Method 119
5.4 Mechanisms of Mesostructure Formation 119
5.5 Tuning the Structural Properties of Mesoporous Silicas 122
5.5.1 Micellar Mesostructure 123
5.5.2 Type of Mesoporous Structure 128
5.5.3 Mesopore Size 131
5.6 Structural Characterization of Mesoporous Silicas 132
5.7 Synthesis of Spherical Mesoporous Silica Nanoparticles 135
5.7.1 Aerosol-Assisted Synthesis 136
5.7.2 Modified Stöber Method 137
5.8 Organic Functionalization of Ordered Mesoporous Silicas 138
5.8.1 Post-synthesis Functionalization ("Grafting") 139
5.8.2 Co-condensation ("One-Pot" Synthesis) 140
5.8.3 Periodic Mesoporous Organosilicas 141
References 141
6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics 153
Juan Peña López
6.1 A Perspective on the Clinical Application of Alumina and Zirconia 153
6.1.1 Alumina 155
6.1.2 Zirconia 158
6.2 Novel Strategies Based on Alumina and Zirconia Ceramics 160
6.2.1 From Alumina Toughened Zirconia to Alumina Matrix Composite 160
6.2.2 Introduction of Different Species in Zirconia 161
6.2.3 Improvement of Surface Adhesion 162
6.3 Non-oxidized Ceramics 163
6.3.1 Silicon Nitride (Si3N4) 163
6.3.2 Silicon Carbide (SiC) 164
References 164
7. Carbon-based Materials in Biomedicine 175
Mercedes Vila
7.1 Introduction 175
7.2 Carbon Allotropes 175
7.2.1 Pyrolytic Carbon 176
7.2.2 Carbon Fibers 177
7.2.3 Fullerenes 177
7.2.4 Carbon Nanotubes 179
7.2.5 Graphene 181
7.2.6 Diamond and Amorphous Carbon 184
7.3 Carbon Compounds 186
7.3.1 Silicon Carbide 186
7.3.2 Boron Carbide 187
7.3.3 Tungsten Carbide 188
References 188
Part III Material Shaping 193
8. Cements 195
Oscar Castaño and Josep A. Planell
Abbreviations 195
Glossary 196
8.1 Introduction 197
8.1.1 Brief History 197
8.1.2 Definition and Chemistry 199
8.1.3 Description of the Different CaP Cements 200
8.1.4 State of the Art 201
8.2 Calcium Phosphate Cements 206
8.2.1 Types 206
8.2.2 Mechanisms 206
8.2.3 Relevant Experimental Variables 207
8.2.4 Material Characterization 211
8.2.5 Reaction Evolution of Cements 220
8.2.6 Additives and Strategies to Enhance Properties 222
8.2.7 Biological Characterization and Bioactive Behavior 224
8.3 Applications 229
8.3.1 Bone Defect Repair 229
8.3.2 Drug Delivery Systems 232
8.4 Future Trends 232
8.5 Conclusions 233
References 234
9. Bioceramic Coatings for Medical Implants 249
M. Victoria Cabañas
9.1 Introduction 249
9.2 Methods to Modify the Surface of an Implant 250
9.2.1 Deposited Coatings 251
9.2.2 Conversion Coatings 257
9.3 Bioactive Ceramic Coatings 258
9.3.1 Clinical Applications 259
9.3.2 Calcium Phosphates-Based Coatings 260
9.3.3 Silica-based Coatings: Glass and Glass-Ceramics 268
9.3.4 Bioactive Ceramic Layer Formation on a Metallic Substrate 270
9.4 Bioinert Ceramic Coatings 272
9.4.1 Titanium Nitride and Zirconia Coatings 273
9.4.2 Carbon-based Coatings 275
References 279
10. Scaffold Designing 291
Isabel Izquierdo-Barba
10.1 Introduction 291
10.2 Essential Requirements for Bone Tissue Engineering Scaffolds 293
10.3 Scaffold Processing Techniques 296
10.3.1 Foam Scaffolds 297
10.3.2 Rapid Prototyping Scaffolds 301
10.3.3 Electrospinning Scaffolds 305
References 307
Part IV Research on Future Ceramics 315
11. Bone Biology and Regeneration 317
Soledad Pérez-Amodio and Elisabeth Engel
11.1 Introduction 317
11.2 The Skeleton 318
11.3 Bone Remodeling 320
11.4 Bone Cells 322
11.4.1 Bone Lining Cells 322
11.4.2 Osteoblasts 323
11.4.3 Osteocytes 323
11.4.4 Osteoclasts 324
11.5 Bone Extracellular Matrix 327
11.6 Bone Diseases 327
11.6.1 Osteoporosis 328
11.6.2 Paget's Disease 329
11.6.3 Osteomalacia 329
11.6.4 Osteogenesis Imperfecta 329
11.7 Bone Mechanics 329
11.8 Bone Tissue Regeneration 333
11.8.1 Calcium Phosphate and Silica-based Bioceramics 333
11.8.2 Bioactive Glasses 334
11.8.3 Calcium Phosphate Cements 335
11.9 Conclusions 336
References 336
12. Ceramics for Drug Delivery 343
Miguel Manzano
12.1 Introduction 343
12.2 Drug Delivery 344
12.3 Drug Delivery from Calcium Phosphates 346
12.3.1 Drug Delivery from Hydroxyapatite 346
12.3.2 Drug Delivery from Tricalcium Phosphates 348
12.3.3 Drug Delivery from Calcium Phosphate Cements 348
12.4 Drug Delivery from Silica-based Ceramics 351
12.4.1 Drug Delivery from Glasses 351
12.4.2 Drug Delivery from Mesoporous Silica 355
12.5 Drug Delivery from Carbon Nanotubes 363
12.6 Drug Delivery from Ceramic Coatings 365
References 366
13. Ceramics for Gene Transfection 383
Blanca González
13.1 Gene Transfection 383
13.2 Gene Transfection Based on Nonviral Vectors 386
13.3 Ceramic Nanoparticles for Gene Transfection 388
13.3.1 Calcium Phosphate Nanoparticles 391
13.3.2 Mesoporous Silica Nanoparticles 393
13.3.3 Carbon Allotropes (Fullerenes, CNTs, Graphene Oxide) 397
13.3.4 Magnetic Iron Oxide Nanoparticles 403
References 410
14. Ceramic Nanoparticles for Cancer Treatment 421
Alejandro Baeza
14.1 Delivery of Nanocarriers to Solid Tumors 421
14.1.1 Special Issues of Tumor Vasculature: Enhanced Permeation and
Retention Effect (EPR) 422
14.1.2 Tumor Microenvironment 423
14.2 Ceramic Nanoparticle Pharmacokinetics in Cancer Treatment 424
14.2.1 Biodistribution and Excretion/Clearance Pathways 424
14.2.2 Toxicity of the Ceramic Nanoparticles 426
14.3 Cancer-targeted Therapy 428
14.3.1 Endocytic Mechanism of Targeted Drug Delivery 428
14.3.2 Specific Tumor Active Targeting 430
14.3.3 Angiogenesis-associated Active Targeting 432
14.4 Ceramic Nanoparticles for Cancer Treatment 434
14.4.1 Mesoporous Silica Nanoparticles 434
14.4.2 Calcium Phosphates Nanoparticles 440
14.4.3 Carbon Allotropes 440
14.4.4 Iron Oxide Nanoparticles and Hyperthermia 442
14.5 Imaging and Theranostic Applications 443
References 446
Index 457
Preface xv
Part I Introduction 1
1. Bioceramics 3
María Vallet-Regí
1.1 Introduction 3
1.2 Reactivity of the Bioceramics 4
1.3 First, Second, and Third Generations of Bioceramics 6
1.4 Multidisciplinary Field 7
1.5 Solutions for Bone Repairing 8
1.6 Biomedical Engineering 13
Recommended Reading 15
2. Biomimetics 17
María Vallet-Regí
2.1 Biomimetics 17
2.2 Formation of Hard Tissues 18
2.3 Biominerals versus Biomaterials 19
Recommended Reading 22
Part II Materials 23
3. Calcium Phosphate Bioceramics 25
Daniel Arcos
3.1 History of Calcium Phosphate Biomaterials 25
3.2 Generalities of Calcium Phosphates 26
3.3 In vivo Response of Calcium Phosphate Bioceramics 28
3.4 Calcium Hydroxyapatite-Based Bioceramics 30
3.4.1 Stoichiometric Hydroxyapatite (HA) 31
3.4.2 Calcium Deficient Hydroxyapatites (CDHA) 37
3.4.3 Carbonated Hydroxyapatites (CHA) 39
3.4.4 Silicon-Substituted Hydroxyapatite (Si-HA) 40
3.4.5 Hydroxyapatites of Natural Origin 45
3.5 Tricalcium Phosphate-Based Bioceramics 50
3.5.1 -Tricalcium Phosphate (-TCP) 50
3.5.2 -Tricalcium Phosphate (-TCP) 53
3.6 Biphasic Calcium Phosphates (BCP) 55
3.6.1 Chemical and Structural Properties 55
3.6.2 Preparation Methods 56
3.6.3 Clinical Applications 56
3.7 Calcium Phosphate Nanoparticles 57
3.7.1 General Properties and Scope of Calcium Phosphate Nanoparticles 57
3.7.2 Preparation Methods of CaP Nanoparticles 58
3.7.3 Clinical Applications 60
3.8 Calcium Phosphate Advanced Biomaterials 60
3.8.1 Scaffolds for in situ Bone Regeneration and Tissue Engineering 60
3.8.2 Drug Delivery Systems 62
References 65
4. Silica-based Ceramics: Glasses 73
Antonio J. Salinas
4.1 Introduction 73
4.1.1 What Is a Glass? 73
4.1.2 Properties of Glasses 75
4.1.3 Structure of Glasses 75
4.1.4 Synthesis of Glasses 76
4.2 Glasses as Biomaterials 78
4.2.1 First Bioactive Glasses (BGs): Melt-Prepared Glasses (MPGs) 79
4.2.2 Other Bioactive MPGs 80
4.2.3 Bioactivity Index and Network Connectivity 80
4.2.4 Mechanism of Bioactivity 81
4.3 Increasing the Bioactivity of Glasses: New Methods of Synthesis 82
4.3.1 Sol-Gel Glasses (SGGs) 82
4.3.2 Composition, Texture, and Bioactivity of SSGs 84
4.3.3 Biocompatibility of SGGs 86
4.3.4 SGGs as Bioactivity Accelerators in Biphasic Materials 86
4.3.5 Template Glasses (TGs) Bioactive Glasses with Ordered Mesoporosity 88
4.3.6 Atomic Length Scale in BGs: How the Local Structure Affects
Bioactivity 91
4.3.7 New Reformulation of Hench's Mechanism for TGs 93
4.3.8 Including Therapeutic Inorganic Ions in the Glass Composition 94
4.4 Strengthening and Adding New Capabilities to Bioactive Glasses 95
4.4.1 Glass Ceramics (GCs) 95
4.4.2 Composites Containing Bioactive Glasses 97
4.4.3 Sol-Gel Organic-Inorganic Hybrids (O-IHs) 98
4.5 Non-silicate Glasses 99
4.5.1 Phosphate Glasses 99
4.5.2 Borate Glasses 100
4.6 Clinical Applications of Glasses 101
4.6.1 Bioactive Silica Glasses 101
4.6.2 Inert Silica Glasses 106
4.6.3 Phosphate Glasses 106
4.6.4 Borate Glasses 107
Recommended Reading 107
5. Silica-based Ceramics: Mesoporous Silica 109
Montserrat Colilla
5.1 Introduction 109
5.2 Discovery of Ordered Mesoporous Silicas 110
5.3 Synthesis of Ordered Mesoporous Silicas 111
5.3.1 Hydrothermal Synthesis 112
5.3.2 Evaporation-Induced Self-Assembly (EISA) Method 119
5.4 Mechanisms of Mesostructure Formation 119
5.5 Tuning the Structural Properties of Mesoporous Silicas 122
5.5.1 Micellar Mesostructure 123
5.5.2 Type of Mesoporous Structure 128
5.5.3 Mesopore Size 131
5.6 Structural Characterization of Mesoporous Silicas 132
5.7 Synthesis of Spherical Mesoporous Silica Nanoparticles 135
5.7.1 Aerosol-Assisted Synthesis 136
5.7.2 Modified Stöber Method 137
5.8 Organic Functionalization of Ordered Mesoporous Silicas 138
5.8.1 Post-synthesis Functionalization ("Grafting") 139
5.8.2 Co-condensation ("One-Pot" Synthesis) 140
5.8.3 Periodic Mesoporous Organosilicas 141
References 141
6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics 153
Juan Peña López
6.1 A Perspective on the Clinical Application of Alumina and Zirconia 153
6.1.1 Alumina 155
6.1.2 Zirconia 158
6.2 Novel Strategies Based on Alumina and Zirconia Ceramics 160
6.2.1 From Alumina Toughened Zirconia to Alumina Matrix Composite 160
6.2.2 Introduction of Different Species in Zirconia 161
6.2.3 Improvement of Surface Adhesion 162
6.3 Non-oxidized Ceramics 163
6.3.1 Silicon Nitride (Si3N4) 163
6.3.2 Silicon Carbide (SiC) 164
References 164
7. Carbon-based Materials in Biomedicine 175
Mercedes Vila
7.1 Introduction 175
7.2 Carbon Allotropes 175
7.2.1 Pyrolytic Carbon 176
7.2.2 Carbon Fibers 177
7.2.3 Fullerenes 177
7.2.4 Carbon Nanotubes 179
7.2.5 Graphene 181
7.2.6 Diamond and Amorphous Carbon 184
7.3 Carbon Compounds 186
7.3.1 Silicon Carbide 186
7.3.2 Boron Carbide 187
7.3.3 Tungsten Carbide 188
References 188
Part III Material Shaping 193
8. Cements 195
Oscar Castaño and Josep A. Planell
Abbreviations 195
Glossary 196
8.1 Introduction 197
8.1.1 Brief History 197
8.1.2 Definition and Chemistry 199
8.1.3 Description of the Different CaP Cements 200
8.1.4 State of the Art 201
8.2 Calcium Phosphate Cements 206
8.2.1 Types 206
8.2.2 Mechanisms 206
8.2.3 Relevant Experimental Variables 207
8.2.4 Material Characterization 211
8.2.5 Reaction Evolution of Cements 220
8.2.6 Additives and Strategies to Enhance Properties 222
8.2.7 Biological Characterization and Bioactive Behavior 224
8.3 Applications 229
8.3.1 Bone Defect Repair 229
8.3.2 Drug Delivery Systems 232
8.4 Future Trends 232
8.5 Conclusions 233
References 234
9. Bioceramic Coatings for Medical Implants 249
M. Victoria Cabañas
9.1 Introduction 249
9.2 Methods to Modify the Surface of an Implant 250
9.2.1 Deposited Coatings 251
9.2.2 Conversion Coatings 257
9.3 Bioactive Ceramic Coatings 258
9.3.1 Clinical Applications 259
9.3.2 Calcium Phosphates-Based Coatings 260
9.3.3 Silica-based Coatings: Glass and Glass-Ceramics 268
9.3.4 Bioactive Ceramic Layer Formation on a Metallic Substrate 270
9.4 Bioinert Ceramic Coatings 272
9.4.1 Titanium Nitride and Zirconia Coatings 273
9.4.2 Carbon-based Coatings 275
References 279
10. Scaffold Designing 291
Isabel Izquierdo-Barba
10.1 Introduction 291
10.2 Essential Requirements for Bone Tissue Engineering Scaffolds 293
10.3 Scaffold Processing Techniques 296
10.3.1 Foam Scaffolds 297
10.3.2 Rapid Prototyping Scaffolds 301
10.3.3 Electrospinning Scaffolds 305
References 307
Part IV Research on Future Ceramics 315
11. Bone Biology and Regeneration 317
Soledad Pérez-Amodio and Elisabeth Engel
11.1 Introduction 317
11.2 The Skeleton 318
11.3 Bone Remodeling 320
11.4 Bone Cells 322
11.4.1 Bone Lining Cells 322
11.4.2 Osteoblasts 323
11.4.3 Osteocytes 323
11.4.4 Osteoclasts 324
11.5 Bone Extracellular Matrix 327
11.6 Bone Diseases 327
11.6.1 Osteoporosis 328
11.6.2 Paget's Disease 329
11.6.3 Osteomalacia 329
11.6.4 Osteogenesis Imperfecta 329
11.7 Bone Mechanics 329
11.8 Bone Tissue Regeneration 333
11.8.1 Calcium Phosphate and Silica-based Bioceramics 333
11.8.2 Bioactive Glasses 334
11.8.3 Calcium Phosphate Cements 335
11.9 Conclusions 336
References 336
12. Ceramics for Drug Delivery 343
Miguel Manzano
12.1 Introduction 343
12.2 Drug Delivery 344
12.3 Drug Delivery from Calcium Phosphates 346
12.3.1 Drug Delivery from Hydroxyapatite 346
12.3.2 Drug Delivery from Tricalcium Phosphates 348
12.3.3 Drug Delivery from Calcium Phosphate Cements 348
12.4 Drug Delivery from Silica-based Ceramics 351
12.4.1 Drug Delivery from Glasses 351
12.4.2 Drug Delivery from Mesoporous Silica 355
12.5 Drug Delivery from Carbon Nanotubes 363
12.6 Drug Delivery from Ceramic Coatings 365
References 366
13. Ceramics for Gene Transfection 383
Blanca González
13.1 Gene Transfection 383
13.2 Gene Transfection Based on Nonviral Vectors 386
13.3 Ceramic Nanoparticles for Gene Transfection 388
13.3.1 Calcium Phosphate Nanoparticles 391
13.3.2 Mesoporous Silica Nanoparticles 393
13.3.3 Carbon Allotropes (Fullerenes, CNTs, Graphene Oxide) 397
13.3.4 Magnetic Iron Oxide Nanoparticles 403
References 410
14. Ceramic Nanoparticles for Cancer Treatment 421
Alejandro Baeza
14.1 Delivery of Nanocarriers to Solid Tumors 421
14.1.1 Special Issues of Tumor Vasculature: Enhanced Permeation and
Retention Effect (EPR) 422
14.1.2 Tumor Microenvironment 423
14.2 Ceramic Nanoparticle Pharmacokinetics in Cancer Treatment 424
14.2.1 Biodistribution and Excretion/Clearance Pathways 424
14.2.2 Toxicity of the Ceramic Nanoparticles 426
14.3 Cancer-targeted Therapy 428
14.3.1 Endocytic Mechanism of Targeted Drug Delivery 428
14.3.2 Specific Tumor Active Targeting 430
14.3.3 Angiogenesis-associated Active Targeting 432
14.4 Ceramic Nanoparticles for Cancer Treatment 434
14.4.1 Mesoporous Silica Nanoparticles 434
14.4.2 Calcium Phosphates Nanoparticles 440
14.4.3 Carbon Allotropes 440
14.4.4 Iron Oxide Nanoparticles and Hyperthermia 442
14.5 Imaging and Theranostic Applications 443
References 446
Index 457
List of Contributors xiii
Preface xv
Part I Introduction 1
1. Bioceramics 3
María Vallet-Regí
1.1 Introduction 3
1.2 Reactivity of the Bioceramics 4
1.3 First, Second, and Third Generations of Bioceramics 6
1.4 Multidisciplinary Field 7
1.5 Solutions for Bone Repairing 8
1.6 Biomedical Engineering 13
Recommended Reading 15
2. Biomimetics 17
María Vallet-Regí
2.1 Biomimetics 17
2.2 Formation of Hard Tissues 18
2.3 Biominerals versus Biomaterials 19
Recommended Reading 22
Part II Materials 23
3. Calcium Phosphate Bioceramics 25
Daniel Arcos
3.1 History of Calcium Phosphate Biomaterials 25
3.2 Generalities of Calcium Phosphates 26
3.3 In vivo Response of Calcium Phosphate Bioceramics 28
3.4 Calcium Hydroxyapatite-Based Bioceramics 30
3.4.1 Stoichiometric Hydroxyapatite (HA) 31
3.4.2 Calcium Deficient Hydroxyapatites (CDHA) 37
3.4.3 Carbonated Hydroxyapatites (CHA) 39
3.4.4 Silicon-Substituted Hydroxyapatite (Si-HA) 40
3.4.5 Hydroxyapatites of Natural Origin 45
3.5 Tricalcium Phosphate-Based Bioceramics 50
3.5.1 -Tricalcium Phosphate (-TCP) 50
3.5.2 -Tricalcium Phosphate (-TCP) 53
3.6 Biphasic Calcium Phosphates (BCP) 55
3.6.1 Chemical and Structural Properties 55
3.6.2 Preparation Methods 56
3.6.3 Clinical Applications 56
3.7 Calcium Phosphate Nanoparticles 57
3.7.1 General Properties and Scope of Calcium Phosphate Nanoparticles 57
3.7.2 Preparation Methods of CaP Nanoparticles 58
3.7.3 Clinical Applications 60
3.8 Calcium Phosphate Advanced Biomaterials 60
3.8.1 Scaffolds for in situ Bone Regeneration and Tissue Engineering 60
3.8.2 Drug Delivery Systems 62
References 65
4. Silica-based Ceramics: Glasses 73
Antonio J. Salinas
4.1 Introduction 73
4.1.1 What Is a Glass? 73
4.1.2 Properties of Glasses 75
4.1.3 Structure of Glasses 75
4.1.4 Synthesis of Glasses 76
4.2 Glasses as Biomaterials 78
4.2.1 First Bioactive Glasses (BGs): Melt-Prepared Glasses (MPGs) 79
4.2.2 Other Bioactive MPGs 80
4.2.3 Bioactivity Index and Network Connectivity 80
4.2.4 Mechanism of Bioactivity 81
4.3 Increasing the Bioactivity of Glasses: New Methods of Synthesis 82
4.3.1 Sol-Gel Glasses (SGGs) 82
4.3.2 Composition, Texture, and Bioactivity of SSGs 84
4.3.3 Biocompatibility of SGGs 86
4.3.4 SGGs as Bioactivity Accelerators in Biphasic Materials 86
4.3.5 Template Glasses (TGs) Bioactive Glasses with Ordered Mesoporosity 88
4.3.6 Atomic Length Scale in BGs: How the Local Structure Affects
Bioactivity 91
4.3.7 New Reformulation of Hench's Mechanism for TGs 93
4.3.8 Including Therapeutic Inorganic Ions in the Glass Composition 94
4.4 Strengthening and Adding New Capabilities to Bioactive Glasses 95
4.4.1 Glass Ceramics (GCs) 95
4.4.2 Composites Containing Bioactive Glasses 97
4.4.3 Sol-Gel Organic-Inorganic Hybrids (O-IHs) 98
4.5 Non-silicate Glasses 99
4.5.1 Phosphate Glasses 99
4.5.2 Borate Glasses 100
4.6 Clinical Applications of Glasses 101
4.6.1 Bioactive Silica Glasses 101
4.6.2 Inert Silica Glasses 106
4.6.3 Phosphate Glasses 106
4.6.4 Borate Glasses 107
Recommended Reading 107
5. Silica-based Ceramics: Mesoporous Silica 109
Montserrat Colilla
5.1 Introduction 109
5.2 Discovery of Ordered Mesoporous Silicas 110
5.3 Synthesis of Ordered Mesoporous Silicas 111
5.3.1 Hydrothermal Synthesis 112
5.3.2 Evaporation-Induced Self-Assembly (EISA) Method 119
5.4 Mechanisms of Mesostructure Formation 119
5.5 Tuning the Structural Properties of Mesoporous Silicas 122
5.5.1 Micellar Mesostructure 123
5.5.2 Type of Mesoporous Structure 128
5.5.3 Mesopore Size 131
5.6 Structural Characterization of Mesoporous Silicas 132
5.7 Synthesis of Spherical Mesoporous Silica Nanoparticles 135
5.7.1 Aerosol-Assisted Synthesis 136
5.7.2 Modified Stöber Method 137
5.8 Organic Functionalization of Ordered Mesoporous Silicas 138
5.8.1 Post-synthesis Functionalization ("Grafting") 139
5.8.2 Co-condensation ("One-Pot" Synthesis) 140
5.8.3 Periodic Mesoporous Organosilicas 141
References 141
6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics 153
Juan Peña López
6.1 A Perspective on the Clinical Application of Alumina and Zirconia 153
6.1.1 Alumina 155
6.1.2 Zirconia 158
6.2 Novel Strategies Based on Alumina and Zirconia Ceramics 160
6.2.1 From Alumina Toughened Zirconia to Alumina Matrix Composite 160
6.2.2 Introduction of Different Species in Zirconia 161
6.2.3 Improvement of Surface Adhesion 162
6.3 Non-oxidized Ceramics 163
6.3.1 Silicon Nitride (Si3N4) 163
6.3.2 Silicon Carbide (SiC) 164
References 164
7. Carbon-based Materials in Biomedicine 175
Mercedes Vila
7.1 Introduction 175
7.2 Carbon Allotropes 175
7.2.1 Pyrolytic Carbon 176
7.2.2 Carbon Fibers 177
7.2.3 Fullerenes 177
7.2.4 Carbon Nanotubes 179
7.2.5 Graphene 181
7.2.6 Diamond and Amorphous Carbon 184
7.3 Carbon Compounds 186
7.3.1 Silicon Carbide 186
7.3.2 Boron Carbide 187
7.3.3 Tungsten Carbide 188
References 188
Part III Material Shaping 193
8. Cements 195
Oscar Castaño and Josep A. Planell
Abbreviations 195
Glossary 196
8.1 Introduction 197
8.1.1 Brief History 197
8.1.2 Definition and Chemistry 199
8.1.3 Description of the Different CaP Cements 200
8.1.4 State of the Art 201
8.2 Calcium Phosphate Cements 206
8.2.1 Types 206
8.2.2 Mechanisms 206
8.2.3 Relevant Experimental Variables 207
8.2.4 Material Characterization 211
8.2.5 Reaction Evolution of Cements 220
8.2.6 Additives and Strategies to Enhance Properties 222
8.2.7 Biological Characterization and Bioactive Behavior 224
8.3 Applications 229
8.3.1 Bone Defect Repair 229
8.3.2 Drug Delivery Systems 232
8.4 Future Trends 232
8.5 Conclusions 233
References 234
9. Bioceramic Coatings for Medical Implants 249
M. Victoria Cabañas
9.1 Introduction 249
9.2 Methods to Modify the Surface of an Implant 250
9.2.1 Deposited Coatings 251
9.2.2 Conversion Coatings 257
9.3 Bioactive Ceramic Coatings 258
9.3.1 Clinical Applications 259
9.3.2 Calcium Phosphates-Based Coatings 260
9.3.3 Silica-based Coatings: Glass and Glass-Ceramics 268
9.3.4 Bioactive Ceramic Layer Formation on a Metallic Substrate 270
9.4 Bioinert Ceramic Coatings 272
9.4.1 Titanium Nitride and Zirconia Coatings 273
9.4.2 Carbon-based Coatings 275
References 279
10. Scaffold Designing 291
Isabel Izquierdo-Barba
10.1 Introduction 291
10.2 Essential Requirements for Bone Tissue Engineering Scaffolds 293
10.3 Scaffold Processing Techniques 296
10.3.1 Foam Scaffolds 297
10.3.2 Rapid Prototyping Scaffolds 301
10.3.3 Electrospinning Scaffolds 305
References 307
Part IV Research on Future Ceramics 315
11. Bone Biology and Regeneration 317
Soledad Pérez-Amodio and Elisabeth Engel
11.1 Introduction 317
11.2 The Skeleton 318
11.3 Bone Remodeling 320
11.4 Bone Cells 322
11.4.1 Bone Lining Cells 322
11.4.2 Osteoblasts 323
11.4.3 Osteocytes 323
11.4.4 Osteoclasts 324
11.5 Bone Extracellular Matrix 327
11.6 Bone Diseases 327
11.6.1 Osteoporosis 328
11.6.2 Paget's Disease 329
11.6.3 Osteomalacia 329
11.6.4 Osteogenesis Imperfecta 329
11.7 Bone Mechanics 329
11.8 Bone Tissue Regeneration 333
11.8.1 Calcium Phosphate and Silica-based Bioceramics 333
11.8.2 Bioactive Glasses 334
11.8.3 Calcium Phosphate Cements 335
11.9 Conclusions 336
References 336
12. Ceramics for Drug Delivery 343
Miguel Manzano
12.1 Introduction 343
12.2 Drug Delivery 344
12.3 Drug Delivery from Calcium Phosphates 346
12.3.1 Drug Delivery from Hydroxyapatite 346
12.3.2 Drug Delivery from Tricalcium Phosphates 348
12.3.3 Drug Delivery from Calcium Phosphate Cements 348
12.4 Drug Delivery from Silica-based Ceramics 351
12.4.1 Drug Delivery from Glasses 351
12.4.2 Drug Delivery from Mesoporous Silica 355
12.5 Drug Delivery from Carbon Nanotubes 363
12.6 Drug Delivery from Ceramic Coatings 365
References 366
13. Ceramics for Gene Transfection 383
Blanca González
13.1 Gene Transfection 383
13.2 Gene Transfection Based on Nonviral Vectors 386
13.3 Ceramic Nanoparticles for Gene Transfection 388
13.3.1 Calcium Phosphate Nanoparticles 391
13.3.2 Mesoporous Silica Nanoparticles 393
13.3.3 Carbon Allotropes (Fullerenes, CNTs, Graphene Oxide) 397
13.3.4 Magnetic Iron Oxide Nanoparticles 403
References 410
14. Ceramic Nanoparticles for Cancer Treatment 421
Alejandro Baeza
14.1 Delivery of Nanocarriers to Solid Tumors 421
14.1.1 Special Issues of Tumor Vasculature: Enhanced Permeation and
Retention Effect (EPR) 422
14.1.2 Tumor Microenvironment 423
14.2 Ceramic Nanoparticle Pharmacokinetics in Cancer Treatment 424
14.2.1 Biodistribution and Excretion/Clearance Pathways 424
14.2.2 Toxicity of the Ceramic Nanoparticles 426
14.3 Cancer-targeted Therapy 428
14.3.1 Endocytic Mechanism of Targeted Drug Delivery 428
14.3.2 Specific Tumor Active Targeting 430
14.3.3 Angiogenesis-associated Active Targeting 432
14.4 Ceramic Nanoparticles for Cancer Treatment 434
14.4.1 Mesoporous Silica Nanoparticles 434
14.4.2 Calcium Phosphates Nanoparticles 440
14.4.3 Carbon Allotropes 440
14.4.4 Iron Oxide Nanoparticles and Hyperthermia 442
14.5 Imaging and Theranostic Applications 443
References 446
Index 457
Preface xv
Part I Introduction 1
1. Bioceramics 3
María Vallet-Regí
1.1 Introduction 3
1.2 Reactivity of the Bioceramics 4
1.3 First, Second, and Third Generations of Bioceramics 6
1.4 Multidisciplinary Field 7
1.5 Solutions for Bone Repairing 8
1.6 Biomedical Engineering 13
Recommended Reading 15
2. Biomimetics 17
María Vallet-Regí
2.1 Biomimetics 17
2.2 Formation of Hard Tissues 18
2.3 Biominerals versus Biomaterials 19
Recommended Reading 22
Part II Materials 23
3. Calcium Phosphate Bioceramics 25
Daniel Arcos
3.1 History of Calcium Phosphate Biomaterials 25
3.2 Generalities of Calcium Phosphates 26
3.3 In vivo Response of Calcium Phosphate Bioceramics 28
3.4 Calcium Hydroxyapatite-Based Bioceramics 30
3.4.1 Stoichiometric Hydroxyapatite (HA) 31
3.4.2 Calcium Deficient Hydroxyapatites (CDHA) 37
3.4.3 Carbonated Hydroxyapatites (CHA) 39
3.4.4 Silicon-Substituted Hydroxyapatite (Si-HA) 40
3.4.5 Hydroxyapatites of Natural Origin 45
3.5 Tricalcium Phosphate-Based Bioceramics 50
3.5.1 -Tricalcium Phosphate (-TCP) 50
3.5.2 -Tricalcium Phosphate (-TCP) 53
3.6 Biphasic Calcium Phosphates (BCP) 55
3.6.1 Chemical and Structural Properties 55
3.6.2 Preparation Methods 56
3.6.3 Clinical Applications 56
3.7 Calcium Phosphate Nanoparticles 57
3.7.1 General Properties and Scope of Calcium Phosphate Nanoparticles 57
3.7.2 Preparation Methods of CaP Nanoparticles 58
3.7.3 Clinical Applications 60
3.8 Calcium Phosphate Advanced Biomaterials 60
3.8.1 Scaffolds for in situ Bone Regeneration and Tissue Engineering 60
3.8.2 Drug Delivery Systems 62
References 65
4. Silica-based Ceramics: Glasses 73
Antonio J. Salinas
4.1 Introduction 73
4.1.1 What Is a Glass? 73
4.1.2 Properties of Glasses 75
4.1.3 Structure of Glasses 75
4.1.4 Synthesis of Glasses 76
4.2 Glasses as Biomaterials 78
4.2.1 First Bioactive Glasses (BGs): Melt-Prepared Glasses (MPGs) 79
4.2.2 Other Bioactive MPGs 80
4.2.3 Bioactivity Index and Network Connectivity 80
4.2.4 Mechanism of Bioactivity 81
4.3 Increasing the Bioactivity of Glasses: New Methods of Synthesis 82
4.3.1 Sol-Gel Glasses (SGGs) 82
4.3.2 Composition, Texture, and Bioactivity of SSGs 84
4.3.3 Biocompatibility of SGGs 86
4.3.4 SGGs as Bioactivity Accelerators in Biphasic Materials 86
4.3.5 Template Glasses (TGs) Bioactive Glasses with Ordered Mesoporosity 88
4.3.6 Atomic Length Scale in BGs: How the Local Structure Affects
Bioactivity 91
4.3.7 New Reformulation of Hench's Mechanism for TGs 93
4.3.8 Including Therapeutic Inorganic Ions in the Glass Composition 94
4.4 Strengthening and Adding New Capabilities to Bioactive Glasses 95
4.4.1 Glass Ceramics (GCs) 95
4.4.2 Composites Containing Bioactive Glasses 97
4.4.3 Sol-Gel Organic-Inorganic Hybrids (O-IHs) 98
4.5 Non-silicate Glasses 99
4.5.1 Phosphate Glasses 99
4.5.2 Borate Glasses 100
4.6 Clinical Applications of Glasses 101
4.6.1 Bioactive Silica Glasses 101
4.6.2 Inert Silica Glasses 106
4.6.3 Phosphate Glasses 106
4.6.4 Borate Glasses 107
Recommended Reading 107
5. Silica-based Ceramics: Mesoporous Silica 109
Montserrat Colilla
5.1 Introduction 109
5.2 Discovery of Ordered Mesoporous Silicas 110
5.3 Synthesis of Ordered Mesoporous Silicas 111
5.3.1 Hydrothermal Synthesis 112
5.3.2 Evaporation-Induced Self-Assembly (EISA) Method 119
5.4 Mechanisms of Mesostructure Formation 119
5.5 Tuning the Structural Properties of Mesoporous Silicas 122
5.5.1 Micellar Mesostructure 123
5.5.2 Type of Mesoporous Structure 128
5.5.3 Mesopore Size 131
5.6 Structural Characterization of Mesoporous Silicas 132
5.7 Synthesis of Spherical Mesoporous Silica Nanoparticles 135
5.7.1 Aerosol-Assisted Synthesis 136
5.7.2 Modified Stöber Method 137
5.8 Organic Functionalization of Ordered Mesoporous Silicas 138
5.8.1 Post-synthesis Functionalization ("Grafting") 139
5.8.2 Co-condensation ("One-Pot" Synthesis) 140
5.8.3 Periodic Mesoporous Organosilicas 141
References 141
6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics 153
Juan Peña López
6.1 A Perspective on the Clinical Application of Alumina and Zirconia 153
6.1.1 Alumina 155
6.1.2 Zirconia 158
6.2 Novel Strategies Based on Alumina and Zirconia Ceramics 160
6.2.1 From Alumina Toughened Zirconia to Alumina Matrix Composite 160
6.2.2 Introduction of Different Species in Zirconia 161
6.2.3 Improvement of Surface Adhesion 162
6.3 Non-oxidized Ceramics 163
6.3.1 Silicon Nitride (Si3N4) 163
6.3.2 Silicon Carbide (SiC) 164
References 164
7. Carbon-based Materials in Biomedicine 175
Mercedes Vila
7.1 Introduction 175
7.2 Carbon Allotropes 175
7.2.1 Pyrolytic Carbon 176
7.2.2 Carbon Fibers 177
7.2.3 Fullerenes 177
7.2.4 Carbon Nanotubes 179
7.2.5 Graphene 181
7.2.6 Diamond and Amorphous Carbon 184
7.3 Carbon Compounds 186
7.3.1 Silicon Carbide 186
7.3.2 Boron Carbide 187
7.3.3 Tungsten Carbide 188
References 188
Part III Material Shaping 193
8. Cements 195
Oscar Castaño and Josep A. Planell
Abbreviations 195
Glossary 196
8.1 Introduction 197
8.1.1 Brief History 197
8.1.2 Definition and Chemistry 199
8.1.3 Description of the Different CaP Cements 200
8.1.4 State of the Art 201
8.2 Calcium Phosphate Cements 206
8.2.1 Types 206
8.2.2 Mechanisms 206
8.2.3 Relevant Experimental Variables 207
8.2.4 Material Characterization 211
8.2.5 Reaction Evolution of Cements 220
8.2.6 Additives and Strategies to Enhance Properties 222
8.2.7 Biological Characterization and Bioactive Behavior 224
8.3 Applications 229
8.3.1 Bone Defect Repair 229
8.3.2 Drug Delivery Systems 232
8.4 Future Trends 232
8.5 Conclusions 233
References 234
9. Bioceramic Coatings for Medical Implants 249
M. Victoria Cabañas
9.1 Introduction 249
9.2 Methods to Modify the Surface of an Implant 250
9.2.1 Deposited Coatings 251
9.2.2 Conversion Coatings 257
9.3 Bioactive Ceramic Coatings 258
9.3.1 Clinical Applications 259
9.3.2 Calcium Phosphates-Based Coatings 260
9.3.3 Silica-based Coatings: Glass and Glass-Ceramics 268
9.3.4 Bioactive Ceramic Layer Formation on a Metallic Substrate 270
9.4 Bioinert Ceramic Coatings 272
9.4.1 Titanium Nitride and Zirconia Coatings 273
9.4.2 Carbon-based Coatings 275
References 279
10. Scaffold Designing 291
Isabel Izquierdo-Barba
10.1 Introduction 291
10.2 Essential Requirements for Bone Tissue Engineering Scaffolds 293
10.3 Scaffold Processing Techniques 296
10.3.1 Foam Scaffolds 297
10.3.2 Rapid Prototyping Scaffolds 301
10.3.3 Electrospinning Scaffolds 305
References 307
Part IV Research on Future Ceramics 315
11. Bone Biology and Regeneration 317
Soledad Pérez-Amodio and Elisabeth Engel
11.1 Introduction 317
11.2 The Skeleton 318
11.3 Bone Remodeling 320
11.4 Bone Cells 322
11.4.1 Bone Lining Cells 322
11.4.2 Osteoblasts 323
11.4.3 Osteocytes 323
11.4.4 Osteoclasts 324
11.5 Bone Extracellular Matrix 327
11.6 Bone Diseases 327
11.6.1 Osteoporosis 328
11.6.2 Paget's Disease 329
11.6.3 Osteomalacia 329
11.6.4 Osteogenesis Imperfecta 329
11.7 Bone Mechanics 329
11.8 Bone Tissue Regeneration 333
11.8.1 Calcium Phosphate and Silica-based Bioceramics 333
11.8.2 Bioactive Glasses 334
11.8.3 Calcium Phosphate Cements 335
11.9 Conclusions 336
References 336
12. Ceramics for Drug Delivery 343
Miguel Manzano
12.1 Introduction 343
12.2 Drug Delivery 344
12.3 Drug Delivery from Calcium Phosphates 346
12.3.1 Drug Delivery from Hydroxyapatite 346
12.3.2 Drug Delivery from Tricalcium Phosphates 348
12.3.3 Drug Delivery from Calcium Phosphate Cements 348
12.4 Drug Delivery from Silica-based Ceramics 351
12.4.1 Drug Delivery from Glasses 351
12.4.2 Drug Delivery from Mesoporous Silica 355
12.5 Drug Delivery from Carbon Nanotubes 363
12.6 Drug Delivery from Ceramic Coatings 365
References 366
13. Ceramics for Gene Transfection 383
Blanca González
13.1 Gene Transfection 383
13.2 Gene Transfection Based on Nonviral Vectors 386
13.3 Ceramic Nanoparticles for Gene Transfection 388
13.3.1 Calcium Phosphate Nanoparticles 391
13.3.2 Mesoporous Silica Nanoparticles 393
13.3.3 Carbon Allotropes (Fullerenes, CNTs, Graphene Oxide) 397
13.3.4 Magnetic Iron Oxide Nanoparticles 403
References 410
14. Ceramic Nanoparticles for Cancer Treatment 421
Alejandro Baeza
14.1 Delivery of Nanocarriers to Solid Tumors 421
14.1.1 Special Issues of Tumor Vasculature: Enhanced Permeation and
Retention Effect (EPR) 422
14.1.2 Tumor Microenvironment 423
14.2 Ceramic Nanoparticle Pharmacokinetics in Cancer Treatment 424
14.2.1 Biodistribution and Excretion/Clearance Pathways 424
14.2.2 Toxicity of the Ceramic Nanoparticles 426
14.3 Cancer-targeted Therapy 428
14.3.1 Endocytic Mechanism of Targeted Drug Delivery 428
14.3.2 Specific Tumor Active Targeting 430
14.3.3 Angiogenesis-associated Active Targeting 432
14.4 Ceramic Nanoparticles for Cancer Treatment 434
14.4.1 Mesoporous Silica Nanoparticles 434
14.4.2 Calcium Phosphates Nanoparticles 440
14.4.3 Carbon Allotropes 440
14.4.4 Iron Oxide Nanoparticles and Hyperthermia 442
14.5 Imaging and Theranostic Applications 443
References 446
Index 457