Preface ........................................................ XV
List of Authors ............................................... XIX
1 Nanotechnology and Tissue Engineering: The Scaffold
Based Approach ............................................. 1
Lakshmi S. Nair, Subhabrata Bhattacharyya, and Cato
T. Laurencin
1.1 Overview ................................................... 1
1.2 Introduction ............................................... 1
1.3 The Importance of Scaffolds in Tissue Engineering .......... 4
1.4 Structure and Functions of Natural Extracellular Matrix ... 12
1.5 Applications of Nanotechnology in Developing Scaffolds
for Tissue Engineering .................................... 21
1.5.1 Polymeric Nanofiber Scaffolds ...................... 23
1.6 Cell Behavior Towards Nano-based Matrices ................. 39
1.7 Applications of Nano-based Matrices as Scaffolds for
Tissue Engineering ........................................ 43
1.7.1 Stem Cell Adhesion and Differentiation ............. 43
1.7.2 Neural Tissue Engineering .......................... 47
1.7.3 Cardiac and Blood Vessel Tissue Engineering ........ 49
1.7.4 Bone, Ligament and Cartilage Tissue Engineering .... 54
1.8 Conclusions ............................................... 55
References ................................................ 56
2 Polymeric Nanofibers in Tissue Engineering ................ 66
Seow Hoon Saw, Karen Wang, Thomas Yong, and Seeram
Ramakrishna
2.1 Overview .................................................. 66
2.2 Introduction .............................................. 67
2.2.1 History of Tissue Engineering and Nanofibers ....... 67
2.3 Classification of Nanofibers .............................. 69
2.3.1 Synthetic Polymers ................................. 69
2.3.2 Biopolymers ........................................ 69
2.3.3 Copolymers ......................................... 70
2.3.4 Composite Polymers ................................. 70
2.4 Nanofiber Fabrication ..................................... 70
2.4.1 Drawing ............................................ 71
2.4.2 Template Synthesis ................................. 71
2.4.3 Phase Separation ................................... 72
2.4.4 Self-assembly ...................................... 73
2.4.5 Electrospinning .................................... 73
2.5 Degradation and Absorption Kinetics of Nanofiber
Scaffolds Compared with Conventional Scaffolds ............ 74
2.6 Advantages and Disadvantages of Nanofiber Scaffolds
Compared with Other Conventional Scaffolds ................ 76
2.7 Biocompatibility of Nano-structured Tissue Engineered
Implants .................................................. 82
2.8 Applications of Polymeric Nanofibers in Tissue
Engineering ............................................... 87
2.8.1 Ophthalmology ...................................... 89
2.8.2 Liver .............................................. 93
2.8.3 Nerve .............................................. 93
2.8.4 Skin ............................................... 99
2.8.5 Bone and Cartilage ................................ 102
2.8.6 Heart and Vascular Grafts ......................... 105
2.8.7 Stem Cells ........................................ 109
2.9 Innovations in Nanofiber Scaffolds ....................... 111
2.10 Conclusion ............................................... 115
References ............................................... 116
3 Electrospinning Technology for Nanofibrous Scaffolds in
Tissue Engineering ....................................... 135
Wan-Ju Li, Rabie M. Shanti, and Rocky S. Juan
3.1 Introduction ............................................. 135
3.2 Nanofibrous Scaffolds .................................... 138
3.2.1 Fabrication Methods for Nanofibrous Scaffolds ..... 138
3.2.2 The Electrospinning Process ....................... 140
3.2.3 Properties of Electrospun Nanofibrous Scaffolds ... 144
3.3 Current Development of Electrospun Nanofibrous
Scaffolds in Tissue Engineering .......................... 146
3.3.1 Evidence Supporting the Use of Nanofibrous
Scaffolds in Tissue Engineering ................... 146
3.3.2 Biomaterials Electrospun into Nanofibrous
Scaffolds ......................................... 151
3.3.3 Engineered Tissues using Electrospun Nanofibrous
Scaffolds ......................................... 269
3.4 Current Challenges and Future Directions ................. 176
3.5 Conclusion ............................................... 177
References ............................................... 177
4 Nanofibrous Scaffolds and their Biological Effects ....... 188
Laura A. Smith, Jonathan A. Beck, and Peter X. Ma
4.1 Overview ................................................. 188
4.2 Introduction ............................................. 188
4.3 Methods of Formation ..................................... 190
4.3.1 Electrospinning ................................... 190
4.3.2 Self-assembly ..................................... 193
4.3.3 Phase Separation .................................. 194
4.4 Nanofibrous Composite Scaffolds .......................... 298
4.4.1 Inorganic Composites .............................. 199
4.4.2 Surface Modification .............................. 200
4.4.3 Factor Delivery Scaffolds ......................... 201
4.5 Biological Effects of Nanofibers ......................... 202
4.5.1 Attachment ........................................ 202
4.5.2 Proliferation ..................................... 203
4.5.3 Differentiation ................................... 203
4.5.4 Migration ......................................... 204
4.6 Tissue Formation ......................................... 205
4.6.1 Connective Tissue ................................. 205
4.6.2 Neural Tissue ..................................... 207
4.6.3 Cardiovascular Tissue ............................. 208
4.6.4 Liver Tissue ...................................... 208
4.7 Conclusion ............................................... 209
References ............................................... 210
5 Nanophase Biomaterials for Tissue Engineering ............ 216
Ramalingam Murugan and Seeram Ramakrishna
5.1 Introduction: Problems with Current Therapies ............ 226
5.2 Tissue Engineering: A Potential Solution ................. 229
5.3 Stem Cells: The Essentials ............................... 220
5.4 Nanobiomaterials: A New Generation Scaffolding Material .. 223
5.4.1 Characteristics of Scaffold ....................... 225
5.4.2 Types of Scaffolding Materials .................... 227
5.5 Nanofibrous Scaffold Processing: Current Scenarios ....... 237
5.5.1 Self-assembly ..................................... 237
5.5.2 Phase Separation .................................. 239
5.5.3 Electrospinning - A New Approach .................. 240
5.6 Cell-Matrix (Scaffold) Interactions ...................... 244
5.6.1 Cell-Ceramic Scaffold Interactions ................ 244
5.6.2 Cell-Polymer Scaffold Interactions ................ 247
5.7 Concluding Remarks ....................................... 248
Acknowledgments .......................................... 249
Abbreviations ............................................ 249
Glossary ................................................. 250
References ............................................... 252
6 Orthopedic Tissue Engineering Using Nanomaterials ........ 257
Michiko Sato and Thomas J. Webster
6.1 Preface .................................................. 257
6.2 Introduction: Problems with Current Implants ............. 258
6.3 A Potential Solution: Nanotechnology ..................... 259
6.3.1 Current Research Efforts to Improve Implant
Performance Targeted the Nanoscale ................ 260
6.3.2 In Vivo Compared with In Vitro Studies ............ 276
6.4 Considerations and Future Directions ..................... 278
Acknowledgments .......................................... 279
References ............................................... 279
7 Hydroxyapatite Nanocrystals as Bone Tissue Substitute .... 283
Norberto Roveri and Barbara Palazzo
7.1 Overview ................................................. 283
7.2 Introduction ............................................. 284
7.3 Biogenic Hydroxyapatite: Bone and Teeth .................. 284
7.4 Biomimetic Hydroxyapatite: Porous and Substituted
Apatites ................................................. 288
7.5 Biologically Inspired Hydroxyapatite: HA-Collagen
Composites and Coatings .................................. 292
7.6 Functionalized Hydroxyapatite: HA Nanocrystals -
Bioactive Molecules ...................................... 296
7.7 Conclusion and Future Challenges 301 Acknowledgments ..... 301
References ............................................... 302
8 Magnetic Nanoparticles for Tissue Engineering ............ 308
Akira Ito and Hiroyuki Honda
8.1 Introduction ............................................. 308
8.2 Mesenchymal Stem Cell Isolation and Expansion ............ 310
8.2.1 MSC Expansion using MCLs .......................... 320
8.2.2 MSC Isolation and Expansion using AMLs ............ 323
8.3 Mag-seeding .............................................. 326
8.4 Construction of 3D Tissue-like Structure ................. 328
8.4.1 Cell Sheet Engineering using RGD-MCLs ............. 328
8.4.2 Construction of a Keratinocyte Sheet using MCLs ... 322
8.4.3 Delivery of Mag-tissue Engineered RPE Sheet ....... 323
8.4.4 Construction of a Liver-like Structure using
MCLs .............................................. 326
8.4.5 Construction of Tubular Structures using MCLs ..... 328
8.5 Conclusion ............................................... 330
References ............................................... 331
9 Applications and Implications of Single-walled Carbon
Nanotubes in Tissue Engineering .......................... 338
Peter S. McFetridge and Matthias U. Nollert
9.1 Introduction ............................................. 338
9.2 Electromagnetic Fields for Tissue Regeneration ........... 339
9.3 Tissue Engineering ....................................... 340
9.4 SWNT Preparation: Purification and Functionalization ..... 342
9.5 Specific Applications of Carbon Nanotubes in Tissue
Engineering .............................................. 352
9.6 Conclusions .............................................. 355
References ............................................... 355
10 Nanoparticles for Ceil Engineering - A Radical Concept ... 361
Beverly A. Rzigalinski, Igor Danelisen, Elizabeth
T. Strawn, Courtney A. Cohen, and Chengya Liang
10.1 Introduction and Overview ................................ 361
10.2 Free Radicals and Oxidative Stress ....................... 362
10.2.1 Sources of Intracellular Free Radicals ............ 362
10.2.2 Oxidative Stress .................................. 364
10.2.3 Oxidative Stress and Disease ...................... 365
10.3 A Nanotechnological Approach to Oxidative Stress ......... 366
10.3.1 Rare Earth Oxide Nanoparticles - Cerium .......... 367
10.4 Nano-pharmacology ........................................ 374
10.4.1 Absorption ........................................ 375
10.4.2 Distribution, Metabolism, and Excretion ........... 377
10.5 Nanoparticle Antioxidants and Treatment of Disease ....... 377
10.6 Toxicology ............................................... 379
10.7 Summary .................................................. 380
References ............................................... 380
11 Nanoparticles and Nanowires for Cellular Engineering ..... 388
Jessica O. Winter
11.1 Introduction ............................................. 388
11.2 Biological Opportunities at the Nanoscale ................ 389
11.2.1 Nanostructures and Cells .......................... 389
11.2.2 Nanoparticle and Nanowire Synthesis for
Biological Systems ................................ 390
11.2.3 Surface Passivation Strategies .................... 394
11.2.4 Bioconjugation .................................... 395
11.2.5 Toxicity (see also Volume 5 of this Series) ....... 399
11.3 Nanostructures to Modify Cell Adhesion and Migration ..... 400
11.3.1 Cell Adhesion at the Nanoscale .................... 401
11.3.2 Cell Adhesion and Nanoscale Physical Topography ... 402
11.3.3 Cell Adhesion and Nanoscale Chemical Patterns ..... 405
11.3.1 Cytoskeletal Manipulation ......................... 406
11.3.5 Future Applications of Nanostructures for Cell
Adhesion and Migration ............................ 407
11.4 Nanostructure Cellular Entry ............................. 411
11.4.1 Biology of Molecular Delivery ..................... 412
11.4.2 Nanostructure Endocytotic Delivery ................ 412
11.4.3 Other Methods of Cellular Entry ................... 415
11.4.4 Nanoparticle Intracellular Sensing ................ 416
11.4.5 Future Directions ................................. 419
11.5 Intracellular Transport of Nanostructures ................ 421
11.5.1 Biology of Intracellular Transport ................ 422
11.5.2 Actin-based Nanostructure Transport ............... 423
11.5.3 Microtubule-based Nanostructure Transport ......... 424
11.5.4 Future Directions ................................. 424
11.6 Biomolecule Delivery Using Nanostructures ................ 425
11.6.1 Biology of Controlled Delivery .................... 425
11.6.2 Drag Delivery ..................................... 426
11.6.3 Gene Therapy ...................................... 432
11.6.4 Future Directions ................................. 434
11.7 Protein Manipulation ..................................... 437
11.7.1 Biology of Protein Manipulation ................... 438
11.7.2 Manipulation of Free Proteins: Enzymes ............ 438
11.7.3 Manipulation of Bound Proteins: Receptors and
Ion Channels ...................................... 439
11.7.4 Future Directions ................................. 440
11.8 Summary and Conclusions .................................. 441
11.8.1 Summary ........................................... 441
11.8.2 Conclusions ....................................... 443
References ............................................... 444
12 Nanoengineering of Biomaterial Surfaces .................. 461
Ashwath Jayagopal and Venkatram Prasad Shastri
12.1 Introduction ............................................. 461
12.2 Conventional Photolithography ............................ 462
12.3 Electron-beam Lithography ................................ 466
12.4 Soft Lithography ......................................... 468
12.5 Polymer-demixed Nanotopographies ......................... 472
12.6 Star-shaped and other Novel Polymer Structures ........... 474
12.7 Vapor Deposition ......................................... 476
12.8 Self-assembly ............................................ 479
12.9 Particle Blasting ........................................ 482
12.10 Ion Beam and Plasma-guided Surface Engineering .......... 483
12.11 Sol-Gel Technology ...................................... 486
12.12 Nanolithography ......................................... 487
12.13 Laser-guided Strategies ................................. 489
12.14 Rapid Prototyping Techniques ............................ 492
12.15 Conclusions ............................................. 496
Acknowledgments ............................................... 496
References .................................................... 497
Index ......................................................... 506
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