Title Details

Dr. Xiumei Wang is professor of biomaterials science at the school of Materials Science and Engineering in Tsinghua University, China. She obtained her Ph.D. in materials science and engineering from Tsinghua University, then did her postdoctoral research at the Center for Musculoskeletal Research of University of Rochester Medical Center, USA, and the Center for Biomedical Engineering of Massachusetts Institute of Technology, USA, from 2005 to 2008. She is a Fellow of Materials Research Society of China and Fellow of Chinese Society for Biomaterials.

Dr. Murugan Ramalingam is professor at the Centre for Stem Cell Research, Christian Medical College Campus, India, and adjunct professor at the Tohoku University, Japan. He received his Ph.D. in Biomaterials from the University of Madras, India. After several years at the National Institute of Standards and Technology (NIST) and the National Institute of Health (NIH), USA, he joined the WPI Advanced Institute for Materials Research, Japan, and later on the University of Strasbourg, France. He is also a Fellow of the Institute of Nanotechnology, UK, and Fellow of Royal Society of Chemistry, UK.

Dr. Xiangdong Kong is professor at the college of Life Sciences, Zhejiang Sci-Tech University, China. He got the PhD degree in materials and Engineering from Tsinghua University, China. He founded the Institute of Biomaterials and Marine Biological Resources in 2012 and ZSTU-Dentium Joint Research Center, China and Korea, for Biofunctional Materials and Regenerative Medicine in 2014.

Dr. Lingyun Zhao is associate professor of cancer nanotechnology at the school of Materials Science and Engineering (MSE) of Tsinghua University, China. She obtained her PhD degree in Chemical and Biomelecular Engineering from the National University of Singapore (NUS) in 2003 under the supervision of Prof. Feng Si-shen, a pioneer and world leader in nanomedicine. She completed her postdoctoral training in the Chemotherapeutic Lab in NUS and then joined Tsinghua University in 2008.

Preface xvii

Part I Introduction 1

1 Nanobiomaterials: State of the Art 3
JingWang, Huihua Li, Lingling Tian, and Seeram Ramakrishna

1.1 Introduction 3

1.1.1 Properties of Nanobiomaterials 4

1.1.2 Interaction between Nanobiomaterials and Biological System 4

1.1.3 Biocompatibility and Toxicity of Nanobiomaterials 5

1.2 Nanobiomaterials for Tissue Engineering Applications 6

1.2.1 Vascular Tissue Engineering 7

1.2.2 Neural Tissue Engineering 9

1.2.3 Cartilage Tissue Engineering 12

1.2.4 Bone Tissue Engineering 13

1.3 Nanobiomaterials for Drug Delivery Applications 15

1.3.1 Carbon-Based Nanobiomaterials 15

1.3.2 Silica Nanoparticles 17

1.3.3 Polymer-Based Nanomaterials 18

1.4 Nanobiomaterials for Imaging and Biosensing Applications 18

1.4.1 Polymer-Based Nanobiomaterials 19

1.4.2 Quantum-Dot-Based Nanobiomaterials 19

1.4.3 Magnetic Nanoparticles 21

1.4.4 Gold Nanobiomaterials 22

1.4.5 Organic–Inorganic-Based Materials 23

1.4.6 CNT-Based Nanobiomaterials 23

1.5 Conclusions and Perspectives 24

References 25

Part II Classification of Nanobiomaterials 37

2 Metallic Nanobiomaterials 39
Magesh S, Vasanth G, Revathi A, Geetha Manivasagam, and Murugan Ramalingam

2.1 Introduction 39

2.2 Conventional to Ultrafine-Grained Materials – A Novel Transformation 40

2.2.1 Bottom-Up Approach 42

2.2.2 Top-Down Approach 43

2.3 Severe Plastic Deformation (SPD) 43

2.3.1 Equal Channel Angular Pressing (ECAP) 43

2.3.2 High-Pressure Torsion (HPT) 45

2.3.3 Accumulative Roll Bonding (ARB) 46

2.3.4 Other SPD Processes 47

2.3.4.1 Multipass Caliber Rolling (MPCR) 47

2.3.4.2 DisintegratedMelt Deposition (DMD) 47

2.4 Mechanical Behavior of Metallic Nanobiomaterials 48

2.5 Corrosion 49

2.5.1 Corrosion Mechanism 50

2.5.2 Passivation of Metallic Biomaterials 50

2.5.3 Biological Environment and Its Influence on Corrosion of Metallic Biomaterials 51

2.5.4 Corrosion Behavior of Metallic Nanobiomaterials 53

2.6 Wear 54

2.6.1 Wear Assessment 55

2.6.2 Wear Aspects of Metallic Nanobiomaterials 56

2.6.2.1 ImprovedWear Resistance of Metallic Nanobiomaterials 56

2.6.2.2 DetrimentalWear Properties of Metallic Nanobiomaterials 57

2.6.2.3 No Effect 57

2.7 Biocompatibility of Metallic Nanobiomaterials 57

2.8 Biomedical Application of Metallic Nanobiomaterials 59

2.9 Future Aspects 59

References 60

3 Polymeric Nanobiomaterials 65
Deepti Rana, Keerthana Ramasamy, Samad Ahadian, Geetha Manivasagam, XiumeiWang, and Murugan Ramalingam

3.1 Introduction 65

3.2 Types of Polymeric Nanobiomaterials 66

3.3 Polymeric Nanofibers 67

3.4 Polymeric Nanofibers to Provide Microenvironmental Cues 69

3.5 Biological Relevance of Polymeric Nanofibers 71

3.6 Recent Trends in Polymeric Nanofibers 72

3.6.1 Hybrid Nanofibers 72

3.6.2 Gradient Nanofibers 74

3.7 Applications of Nanofibers in RegenerativeMedicine 75

3.7.1 Bone Tissue Engineering 75

3.7.2 Nerve Tissue Engineering 77

3.7.3 Vascular Tissue Engineering 78

3.8 Concluding Remarks 79

Acknowledgment 80

References 80

4 Carbon-Based Nanobiomaterials 85
Samad Ahadian, Farhad Batmanghelich, Raquel Obregón, Deepti Rana, Javier Ramón-Azcón, Ramin Banan Sadeghian, and Murugan Ramalingam

4.1 Introduction 85

4.2 Tissue Engineering 87

4.2.1 Neural Tissue Engineering 87

4.2.1.1 CNTs in Neural Tissue Engineering 88

4.2.1.2 Graphene in Neural Tissue Engineering 89

4.2.2 Bone Tissue Engineering 89

4.2.2.1 CNTs in Bone Tissue Engineering 89

4.2.2.2 Graphene in Bone Tissue Engineering 92

4.3 Gene and Drug Delivery 92

4.3.1 CNTs in Delivery Systems 92

4.3.2 Graphene in Delivery Systems 93

4.4 Biosensing 93

4.4.1 CNTs in Biosensing 93

4.4.2 Graphene in Biosensing 94

4.5 Biomedical Imaging 95

4.5.1 CNTs in Biomedical Imaging 95

4.5.2 Graphene in Biomedical Imaging 95

4.6 Conclusions 97

References 97

Part III Nanotechnology-Based Approaches in Biomaterials Fabrications 105

5 Molecular Self-Assembly for Nanobiomaterial Fabrication 107
Ling Zhu, Yanlian Yang, and ChenWang

5.1 Introduction 107

5.1.1 Molecular Self-Assembly 107

5.1.2 Nanoscale Interactions andTheir Roles in Self-Assembly 107

5.1.3 Technologies for the Characterization of Self-Assemblies 108

5.1.3.1 Microscopies 108

5.1.3.2 Dynamic Light Scattering 110

5.1.3.3 Spectroscopies 110

5.2 Self-Assembling Peptides 111

5.2.1 Peptide Self-Assembly and Its Applications 111

5.2.2 Driving Force for Peptide Self-Assembly 112

5.2.3 Secondary Structures of Peptide Self-Assemblies 112

5.2.3.1 ;;-Sheet-Forming Peptides 112

5.2.3.2 Coiled-Coil Peptides 114

5.2.3.3 Collagen-like Triple-Helical Peptides 114

5.2.3.4 Secondary Structure Transition Peptides 115

5.2.4 Peptide Nanostructures 115

5.2.4.1 Nanofibers and Hydrogel 115

5.2.4.2 Peptide Nanotubes 116

5.2.4.3 Vesicle/Spherical Structures from Surfactant Peptides 118

5.3 Nano-Drug Carriers 118

5.3.1 Liposomes 119

5.3.2 Polymeric Drug Carriers 121

5.3.2.1 Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles 121

5.3.2.2 PEGylation 121

5.3.2.3 Polymeric Micelles 122

5.3.3 Drug Delivery Strategies: Passive Targeting versus Active Targeting 123

5.3.4 Triggered Drug Release 123

5.3.5 Other Applications of Nano-Drug Carriers 124

5.4 Inorganic Nanobiomaterials 124

5.4.1 Graphene 124

5.4.2 Carbon Nanotubes 125

5.4.3 Surface Functionalization of Carbon Nanomaterials for Biomedical Application 126

5.4.3.1 Surface Functionalization of Graphene 126

5.4.3.2 Graphene–Peptide Hybrids 126

5.4.3.3 Layer-by-Layer Assembly of Graphene Films 127

5.4.3.4 Application of Functionalized Graphene 127

5.4.3.5 Surface Functionalization of Carbon Nanotubes 128

5.4.3.6 Application of Functionalized Carbon Nanotubes 128

5.5 Perspectives 129

Acknowledgments 129

References 129

6 Electrospraying and Electrospinning for Nanobiomaterial Fabrication 143
Liumin He, Yuyuan Zhao, Lingling Tian, and Seeram Ramakrishna

6.1 Introduction 143

6.2 What is Electrospinning? 143

6.2.1 The Electrospinning Process 144

6.2.2 The Electrospinning Device 144

6.2.3 Advances in Electrospinning Devices 146

6.2.3.1 Advances in the Collector 146

6.2.3.2 Advances in the Spinneret 146

6.3 Key Considerations in Electrospinning 146

6.3.1 The Spinnable Materials 146

6.3.1.1 Biopolymers 147

6.3.1.2 Water-Soluble Polymers 147

6.3.1.3 Organosoluble Polymers 147

6.3.1.4 Biodegradable Polymers 147

6.3.1.5 Copolymers 148

6.3.1.6 Melt-Electrospinnable Polymers 148

6.3.2 Parameters in Electrospinning 148

6.3.2.1 Solution Properties 148

6.3.2.2 Process Parameters 150

6.3.2.3 Ambient Parameters 151

6.3.2.4 Conclusion 151

6.4 The Application of Electrospun Materials in Biomedicine 151

6.4.1 Tissue Engineering Applications 151

6.4.1.1 Vascular Tissue Engineering 152

6.4.1.2 Bone Tissue Engineering 152

6.4.1.3 Nerve Tissue Engineering 153

6.4.1.4 Skin Tissue Engineering 154

6.4.1.5 Tendon and Ligament Tissue Engineering 155

6.4.2 Transport and Release of Drugs 156

6.4.3 Wound Dressing 157

6.5 Future Directions 159

References 159

7 Layer-by-Layer Technique: From Capsule Assembly to Application in Biological Domains 165
Xi Chen

7.1 Definition of Layer-by-Layer (LbL) Assembly 165

7.2 Stabilizing Interactions between LbL Films 166

7.2.1 LbL Assembly via Electrostatic Bonding 167

7.2.2 LbL Assembly via Hydrogen Bonding 168

7.2.3 LbL Assembly via Covalent Bonding 168

7.3 Emerged Technologies Employed for LbL Assembly 169

7.3.1 Immersive LbL Assembly 169

7.3.2 Spin LbL Assembly 169

7.3.3 Spray LbL Assembly 171

7.3.4 Electric and Magnetic LbL Assembly 171

7.3.5 Fluidic LbL Assembly 172

7.4 TypicalMethods for the Assembly of LbL Particles/Capsules 172

7.4.1 Centrifugation 172

7.4.2 Microfluidics 174

7.4.3 Electrophoresis 174

7.5 Application of LbL Capsules in Biological Environment 174

7.5.1 Therapeutic Delivery 174

7.5.2 Biosensors and Bioreactors 175

7.6 LbL Capsules as aTherapeutic Delivery Platform: Cargo Loading and Release 176

7.6.1 Cargo Loading 176

7.6.1.1 Pre-loading 176

7.6.1.2 Post-loading 176

7.6.1.3 Loading Cargo on Capsule Shells 176

7.6.2 Biological Stimuli–Responsive Cargo Release 177

7.6.2.1 Enzyme 177

7.6.2.2 pH 178

7.6.2.3 Redox 178

7.7 The Effect of Physicochemical Properties of LbL Capsules on Cellular Interactions 179

7.7.1 Morphology Effects 179

7.7.2 Surface Property Effects 180

7.7.3 Mechanical Effects 181

7.8 Conclusion and Outlook 182

References 182

8 Nanopatterning Techniques 189
Lakshmi Priya Manickam, Akshay Bhatt, Deepti Rana, Serge Ostrovidov, Renu Pasricha, XiumeiWang, andMurugan Ramalingam

8.1 Introduction 189

8.2 Types of Nanopatterning Techniques 190

8.3 Nano-biopatterning 190

8.4 Chemical Patterning 192

8.5 Topographical Patterning 196

8.6 Combinatorial Patterning 200

8.7 3D Patterning 201

8.8 Factors Influencing Nanopatterning 202

8.9 Concluding Remarks 204

References 204

9 Surface Modification of Metallic Implants with Nanotubular Arrays via Electrochemical Anodization 211
Ming Jin, Shenglian Yao, and LuningWang

9.1 Introduction 211

9.2 Fabrication of Nanotubular Arrays on Metals via Electrochemical Anodization 213

9.2.1 The Influence of Fluoride Concentration on TiO2 Nanotubes 216

9.2.2 The Effect of pH Value on the Formation of TiO2 Nanotubes 218

9.2.3 The Effect of Applied Potential on the Formation of TiO2 Nanotubes 219

9.2.4 The Effect of Anodization Duration on the Formation of TiO2 Nanotubes 219

9.2.5 Nanotube Oxide Layer on Titanium Alloys and Other Metals 220

9.3 Biocompatibility of Metals with Nanotubular Surfaces 223

9.3.1 Hydroxyapatite Formation on Nanotubular Arrays 223

9.3.2 In Vitro Biocompatibility Studies 225

9.3.3 In Vivo Biocompatibility Studies 227

9.3.4 Nanotubular Arrays for Drug Delivery and Other Preload Applications 228

9.4 Conclusion 230

References 230

Part IV Nanobiomaterials in Biomedical Applications: Diagnosis, Imaging, and Therapy 239

10 Nonconventional Biosensors Based on Nanomembrane Materials 241
Lan Yin and Xing Sheng

10.1 Introduction 241

10.2 Soft Electronics 242

10.3 Injectable Electronics 246

10.4 Biodegradable Electronics 248

10.5 Conclusions 252

References 253

11 Nanobiomaterials for Molecular Imaging 259
Prashant Chandrasekharan and Yang Chang-Tong

11.1 Introduction 259

11.1.1 Reporter Nanobiomaterial System for Molecular Imaging 260

11.1.2 Biomaterial Packing for Molecular Imaging 264

11.1.3 Targeting Ligands and Molecular Imaging 268

11.2 Conclusion 272

References 272

12 Engineering Nanobiomaterials for Improved Tissue Regeneration 281
Liping Xie,Wei Qian, Jianjun Sun, and Bo Zou

12.1 Introduction 281

12.2 Extracellular Microenvironment: Role of Nanotopography 282

12.3 Type of Nanobiomaterials for Tissue Engineering 284

12.3.1 Nanoparticles and Nanoclusters 284

12.3.2 Nanofibrous Scaffolds 286

12.3.3 Nanocomposites 288

12.3.3.1 Nanocomposite Hydrogels 289

12.3.3.2 Nanocomposite Sponge 290

12.4 Applications of Nanobiomaterials to Tissue Regeneration 290

12.4.1 Nanobiomaterials for Neural Tissue Engineering 291

12.4.2 Nanobiomaterials for Bone Regeneration 294

12.4.3 Nanobiomaterials for Heart Regeneration 295

12.5 Conclusions and Future Perspectives 296

References 298

13 Nanobiomaterials for Cancer Therapy 305
Wei Tao and Lin Mei

13.1 Introduction 305

13.2 Cancer Pathophysiology 306

13.2.1 Angiogenesis and “Angiogenic Switch” 307

13.2.2 Enhanced Permeability and Retention Effect 309

13.3 Types of Cancer Treatment and Related NBMs 310

13.3.1 Surgery 311

13.3.2 Chemotherapy and NBMs 311

13.3.3 Radiotherapy and NBMs 312

13.3.4 PhotothermicTherapy and NBMs 313

13.3.5 Gene Therapy and NBMs 313

13.3.6 ImmuneTherapy and NBMs 314

13.4 Current NBMs in Cancer Therapy 315

13.4.1 Polymeric NPs 315

13.4.2 Liposomes 316

13.4.3 QDs 317

13.4.4 Inorganic NPs 318

13.4.5 Carbon Nanotubes 319

13.5 Conclusions 319

References 320

14 Chemical Synthesis and Biomedical Applications of Iron Oxide Nanoparticles 329
Jing Yu, Yanmin Ju, Fan Chen, Shenglei Che, Lingyun Zhao, Fenggeng Sheng, and Yanglong Hou

14.1 Introduction 329

14.2 Chemical Synthesis of IONP (Fe3O4) NPs 330

14.2.1 Co-precipitation 330

14.2.2 Thermal Decomposition 331

14.2.3 Hydrothermal Synthesis 333

14.2.4 Microemulsion 334

14.2.5 Sol–Gel Method 334

14.2.6 Polyol Method 335

14.3 Biomedical Applications of IONPs 335

14.3.1 MR Imaging (T1/T2) 337

14.3.2 Magnetic Hyperthermia 340

14.3.3 Magnetic Targeting (Drug Delivery, Gene Delivery) 342

14.3.3.1 Magnetically Controlled Drug Delivery 343

14.3.3.2 Magnetically Controlled Gene Delivery 344

14.3.4 Tissue Engineering 345

14.3.5 Cell Tracking 346

14.4 Conclusion and Perspective 348

References 348

15 Gold Nanoparticles and Their Bioapplications 359
Heyun Shen, Li Cheng, Linlin Li, and Huiyu Liu

15.1 Introduction 359

15.2 The Preparation of Various AuNPs 360

15.2.1 Gold Nanoshells 360

15.2.2 Gold Nanorods 361

15.2.3 Gold Nanocages 362

15.2.4 Gold Nanoclusters 362

15.3 Optical Bioimaging Based on AuNPs 363

15.3.1 AuNPs for OCT Imaging 364

15.3.2 AuNPs for Photoacoustic Imaging 364

15.3.3 AuNPs for SERS Detection and Imaging 365

15.3.4 AuNPs for Multimode Imaging 367

15.3.4.1 Dark-Field Imaging Combined with SERS Imaging 367

15.3.4.2 Fluorescence Imaging Combined with SERS Imaging 368

15.4 AuNPs forTheranostic Integration Platforms 368

15.4.1 Gold Nanoshells for Theranostic Integration Platforms 368

15.4.2 Gold Nanorods for Theranostic Integration Platforms 371

15.4.3 Gold Nanocages forTheranostic Integration Platforms 372

15.5 Conclusions and Perspectives 374

References 375

16 Silicon-Based Nanoparticles for Drug Delivery 379
Yixuan Yu and Xi Liu

16.1 Introduction 379

16.2 Porous Silicon Nanoparticles 380

16.2.1 Synthesis of Porous Silicon Nanoparticles 380

16.2.2 Properties of Porous Silicon Nanoparticles 381

16.2.3 Application of Porous Silicon Nanoparticles in Drug Delivery 383

16.3 Silicon Nanocrystals (Silicon Quantum Dots) 386

16.3.1 Synthesis of Silicon Nanocrystals 386

16.3.2 Surface Chemistry of Silicon Nanocrystals 387

16.3.3 Properties of Silicon Nanocrystals 389

16.3.4 Application of Silicon Nanocrystals in Drug Delivery 391

16.4 Porous Silica Nanoparticles 392

16.4.1 Synthesis of Porous Silica Nanoparticles 392

16.4.2 Tuning the Porous Structure of Silica Nanoparticles 394

16.4.3 Porous Silica Nanoparticles as Drug Delivery Vehicles 395

16.5 Conclusions 396

References 397

17 Dendritic-Polymer-Based Nanomaterials for Cancer Diagnosis and Therapy 403
Na Zhu, Qiyong Gong, Zhongwei Gu, and Kui Luo

17.1 Introduction 403

17.2 Dendritic-Polymer-Based Nanomaterials for Cancer Diagnosis 404

17.2.1 Dendrimers for MRI 404

17.2.2 Dendrimer-Entrapped Gold Nanoparticles for CT Imaging 408

17.2.3 Dendrimers as Optical Nanoprobes 409

17.3 Dendrimers as Drug Carriers for Cancer Therapy 410

17.3.1 Functional Dendritic Polymers for Encapsulation of Anticancer Drugs 410

17.3.2 Chemical Dendritic-Polymer-Drug Conjugates via Peripheral Modification as Anticancer Drug Delivery Systems 411

17.3.3 Dendritic-Polymer-Drug Conjugates of Precise Molecular Structures as Anticancer Drug Nanocarriers 413

17.4 Dendritic Polymers for Theranostics 414

17.4.1 Theranostic Dendrimers for MRI 415

17.4.2 Theronostic Dendrimers for CT Imaging 417

17.4.3 Theranostic Dendritic-Polymer-Based Vehicles for Phototherapy and Fluorescence Imaging 418

17.5 Conclusion and Prospects 420

References 420

Part V Biosafety and Clinical Translation of Nanobiomaterials 429

18 Biosafety of Carbon-Based Nanoparticles and Nanocomposites 431
Yong Cheol Shin, Jong Ho Lee, In-Seop Lee, and Dong-Wook Han

18.1 Introduction 431

18.2 Evaluation of Biosafety of Carbon-Based NMs 432

18.3 Carbon Nanotubes 434

18.3.1 Types and Structures 434

18.3.2 In Vitro Biosafety of CNTs 435

18.3.3 In Vivo Biosafety of CNTs 437

18.4 Graphene and Its Derivatives 439

18.4.1 The Types and Characteristics of Graphene 439

18.4.2 In Vitro Biosafety of Graphene and Its Derivatives 440

18.4.3 In Vivo Biosafety of Graphene and Its Derivatives 443

18.5 Carbon-Based NCs 447

18.5.1 CNT-Based NCs 447

18.5.2 Graphene-Based NCs 448

18.6 Summary and Outlook 450

References 450

19 Clinical Translation and Safety Regulation of Nanobiomaterials 459
Ruibo Zhao, Lawrence Keen, and Xiangdong Kong

19.1 Introduction 459

19.2 Key Examples of Nanobiomaterials in Clinical Applications 460

19.2.1 Liposomal Nanobiomaterials 460

19.2.2 PEG-Coated Nanobiomaterials 462

19.2.3 Polymer Nanobiomaterials 463

19.2.4 Iron Oxide Nanobiomaterials 464

19.2.5 Gold Nanoparticle Nanobiomaterials 464

19.2.6 Silver Nanobiomaterials 465

19.2.7 Quantum Dot (QD) Nanobiomaterials 466

19.2.8 Tissue Engineering Scaffold with Nanostructure 467

19.3 Safety of Nanobiomaterials 467

19.3.1 Influence Factor for Nanosafety 467

19.3.2 Analysis of Nanomaterial Toxicity 469

19.4 Prospective Future of Nanobiomaterials 470

References 471

Index 481