Nanobiomaterials

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 Improved Wear Resistance of Metallic Nanobiomaterials 56
2.6.2.2 Detrimental Wear 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 beta-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

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.