Hydrogels (eBook)

Dr. Vijay Kumar Thakur is currently a Permanent Faculty in the School of Aerospace, Transport and Manufacturing , Cranfield University, UK. Some of his other prior significant appointments include being a Research Scientist in Temasek Laboratories at Nanyang Technological University, Singapore (2009-2012) and a Visiting Research Fellow in the Department of Chemical and Materials Engineering at LHU–Taiwan. He spent his postdoctoral study in Materials Science & Engineering at Iowa State University, USA and received Ph.D. in Polymer Chemistry (2009). In the course of his academic career, he has published more than 100 SCI journal research articles in the field of chemical sciences/materials science and holds one US patent. Among these, ten of his research papers have been highlighted as “Highly Cited Papers” in Web of Science (less than 1% of published papers receive this ranking), while three others have been highlighted as “Hot Papers” (Hot papers are selected by virtue of being cited among the top one-tenth of one percent-0.1%) in a current bimonthly period in Web of Science). He has also published 33 books and 35 book chapters on the advanced state-of-the-art of polymer science/materials science/nanotechnology with numerous publishers. His research interests include the synthesis and processing of bio-based polymers, composites, nanostructured materials, hydrogels, polymer micro/nanocomposites, nanoelectronic materials, novel high dielectric constant materials, engineering nanomaterials, electrochromic materials, green synthesis of nanomaterials, and surface functionalization of polymers/nanomaterials. He sits on the editorial board of several SCI journals as well as Scientific Bodies around the globe. Dr. Manju Kumari Thakur has been working as an assistant professor of Chemistry at the Division of Chemistry, Himachal Pradesh University, Shimla, India since June 2010. She received her B.Sc. in Chemistry, Botany and Zoology; M.Sc., M. Phil in Organic Chemistry and Ph.D. in Polymer Chemistry from the Chemistry Department at Himachal Pradesh University, Shimla, INDIA. She has broad experience in the field of organic chemistry, biopolymers, composites/nanocomposites, hydrogels, applications of hydrogels in the removal of toxic heavy metal ions, drug delivery, etc. She has published more than 30 research papers in several international journals, has co-authored three books, and has also published 25 book chapters in the field of polymeric materials.

Preface 6
Contents 8
About the Editors 10
1 Intelligent Hydrogels as Drug Delivery Systems 12
References 34
2 History, Classification, Properties and Application of Hydrogels: An Overview 40
Abstract 40
1 Historical Background 40
2 Hydrogels 41
3 Classification of Hydrogels 42
3.1 Classification Based on Origin 42
3.1.1 Natural Hydrogels 42
3.1.2 Synthetic Hydrogels 43
3.1.3 Hybrid Hydrogels 43
3.2 Classification Based on Composition 43
3.2.1 Homopolymer Hydrogels 43
3.2.2 Copolymer Hydrogels 43
3.2.3 Multipolymer Hydrogels 44
3.2.4 Interpenetrating Network (IPN) 44
3.3 Classification Based on Ionic Charge 44
3.3.1 Neutral (Non-Ionic) Hydrogels 44
3.3.2 Ionic Hydrogels 44
3.3.3 Ampholytic Hydrogels 44
3.4 Classification Based on Pore Size 45
3.5 Classification Based on Physical Appearance 45
3.6 Classification Based on Configuration 45
3.6.1 Amorphous (Non-Crystalline) 45
3.6.2 Semi-Crystalline 45
3.7 Classification Based on Cross-Linking 45
4 Synthesis of Hydrogels 46
4.1 Chemical Method 46
5 Characteristics of Hydrogels 47
5.1 Temperature-Sensitive Hydrogels 47
5.2 pH-Sensitive Hydrogels 48
6 Applications of Hydrogels 48
6.1 Separation Technology 48
6.2 Biomedical Applications 49
6.3 Pharmaceutical Applications 50
6.4 Agricultural and Horticultural Applications 50
7 Biopolymers—Polysaccharides 51
7.1 Sodium Alginate 51
7.2 Xanthan Gum 51
7.3 Gum Ghatti 51
7.4 Gum Karaya 52
7.5 Gum Arabic 52
7.6 Carrageenans 52
7.7 Chitosan 53
8 Conclusions and Future Perspective 54
References 55
3 Macroporous Hydrogels: Preparation, Properties, and Applications 62
Abstract 62
1 Introduction 64
2 Classification of Macroporous Hydrogels 65
3 Preparation Techniques of Macroporous Hydrogels 66
3.1 Porogen Leaching 67
3.2 Freeze-Drying Technique (Lyophilization) 68
3.3 Ice-Templating (Cryogelation) 69
3.4 Gas Foaming 71
3.5 Electrospinning 71
3.6 Other Preparation Techniques (Colloidal Crystal Templating, 3D Printing, Photolithography) 72
4 Properties of Macroporous Hydrogels 73
4.1 Swelling 73
4.2 Porosity 76
4.3 Mechanical Properties 76
4.4 Thermal Stability 78
4.5 Biodegradability and Biocompatibility 78
5 Applications of Macroporous Hydrogels 80
5.1 Drug Delivery 80
5.2 Tissue Engineering and Regenerative Medicine 82
5.3 Chromatography 85
5.4 Environmental Protection 85
5.4.1 Heavy Metal Ions Sorption 85
5.4.2 Dyes Sorption 87
6 Conclusions 88
Acknowledgements 89
References 89
4 Hydrogel-Based Strategies for Stem Cell Therapy 97
Abstract 97
1 Introduction 98
2 Classifications of Hydrogels 98
2.1 According to the Origin of Hydrogel 99
2.1.1 Plant-Derived Polymer Hydrogels 100
2.1.2 Animal-Derived Polymer Hydrogels 101
2.1.3 Hydrogels Based on Synthetic Polymers 103
2.2 Environmentally-Sensitive Polymer Hydrogels 105
2.2.1 Temperature-Sensitive Hydrogels 105
2.2.2 pH-Sensitive Hydrogels 106
2.2.3 Electro-Sensitive Hydrogels 106
3 Current Status of Stem Cell Survival After Transplantation 107
3.1 Stem Cell Niches 107
3.2 Hydrogel Niches and Their Application in Stem Cell Therapy 108
3.2.1 Hydrogels as ECM 109
3.2.2 Hydrogel with Support Cells 110
3.2.3 Hydrogel with Controlled-Release Strategy 111
4 Conclusions and Future Perspective 114
Acknowledgements 114
References 115
5 Protein- and Nanoparticle-Loaded Hydrogels Studied by Small-Angle Scattering and Rheology Techniques 123
Abstract 123
1 Introduction 124
2 Methods for Investigation of Structural and Viscoelastic Properties in Hydrogels 124
2.1 Structural Characterization by Small-Angle Scattering 124
2.2 Viscoelasticity of Polymer Fluids Probed by Rheology 131
3 Investigation of Rheological and Structural Properties of Protein- and Nanoparticle-Loaded Hydrogels 136
4 Conclusions and Future Perspective 150
References 151
6 Preparation, Properties and Application of Hydrogels: A Review 154
Abstract 154
1 Introduction 154
1.1 What Is Hydrogel? 155
1.2 History of Hydrogel 157
1.3 Types of Hydrogel 158
2 Synthesis Procedures of Hydrogels 158
2.1 Homopolymers 158
2.2 Co-polymers 160
2.3 Semi-interPenetrating Networks (Semi-IPNs) 161
2.4 InterPenetrating Networks (IPNs) 162
3 Significant Properties of Hydrogel 163
3.1 Swelling Properties 163
3.2 Mechanical Properties of Hydrogel 164
3.3 Bio-compatible Properties 165
4 Characterization of Hydrogels 166
4.1 Fourier Transform Infrared Spectroscopy 166
4.2 Atomic Force Microscopy (AFM) 166
4.3 Network Pore Size 166
4.4 X-ray Diffraction 167
4.5 Swelling Behaviour 167
4.6 Crosslinking and Mechanical Strength 167
4.7 Rheology 167
5 Application of Smart Hydrogel 167
5.1 Biomaterial Application 168
5.1.1 Soft Contact Lenses 168
5.1.2 Tissue Regeneration and Tissue Engineering Applications 168
5.1.3 Wound Dressing 169
5.1.4 Drug Delivery 170
5.2 Industrial Applications 172
5.3 Environmental Applications 173
5.3.1 Hydrogels for the Prevention of Soil Erosion 173
5.3.2 Use of Hydrogels for Agricultural Purposes 173
6 Patents on Hydrogels 174
7 Conclusion 176
References 176
7 Hydrogel-Based Stimuli-Responsive Functionalized Graft Copolymers for the Controlled Delivery of 5-Fluorouracil, an Anticancer Drug 183
Abstract 183
1 Introduction 183
2 Experimental 185
2.1 Materials 185
2.2 Preparation of the Drug Carriers 186
2.2.1 3-Methacryloxy Propyl Trimethoxy Silane-Coated Magnetic Nanoparticles Polymerized with Glycidyl Methacrylate-Grafted-Maleated Cyclodextrin [MPTMS-MNP-poly-(GMA-g-MACD)] 186
2.2.2 Aminated-Glycidyl Methacrylate-Grafted Cellulose-Grafted-Polymethacrylic Acid-Succinyl Cyclodextrin [Cell-g-(GMA/en)-PMA-SCD] 186
2.3 Instruments and Methods of Characterization 187
2.4 Experimental 189
2.4.1 Swelling Measurements 189
2.4.2 Drug Encapsulation and Delivery Studies 189
Drug Loading Efficiency (DLE) and Encapsulation Efficiency (EE) 189
In Vitro Release of the Drug 190
Cytotoxicity (3-[4,5-Dimethylthiazol-2-yl]-2,5-Diphenyl Tetrazolium Bromide) (MTT Assay) 190
3 Results and Discussion 191
3.1 Development of DDS and Its Characteristics 191
3.1.1 MPTMS-MNP-poly-(GMA-g-MACD) 191
3.1.2 Cell-g-(GMA/en)-PMA-SCD 191
3.2 Characterization 192
3.2.1 FT-IR Spectra 192
3.2.2 XRD Analysis 193
3.2.3 SEM Analysis 194
3.3 Swelling Behavior 194
3.4 Drug Loading Efficiency (DLE) and Encapsulation Efficiency (EE) 195
3.5 In Vitro Drug Release 196
3.6 Kinetic Modeling of Drug Release 197
3.7 Cytotoxicity Assay 198
4 Conclusions 200
Acknowledgements 201
References 201
8 Emerging Technology in Medical Applications of Hydrogel 204
Abstract 204
1 Introduction 204
2 Preparation of Hydrogel 206
2.1 Chemical Methods to Prepare Hydrogels 207
2.1.1 Cross-linking Polymerization 207
2.1.2 Copolymerization 207
2.1.3 Cross-linking by High Energy Radiation 208
2.1.4 Cross-linking Using Enzymes 208
2.2 Physical Methods to Prepare Hydrogels 209
2.2.1 Cross-linking by Ionic Interaction 209
2.2.2 Cross-linking by Crystallization 209
2.2.3 Hydrogen Bonding in the Cross-linking 210
3 Types of Hydrogels 210
3.1 pH-Sensitive or Ion-Sensitive Hydrogels 210
3.2 Thermo-Sensitive Hydrogel 213
3.3 Glucose-Sensitive Hydrogels 214
3.4 Photosensitive Hydrogels 215
3.5 Magnetically Responsive Hydrogels 215
3.6 Ultrasound Responsive Hydrogels 216
4 Applications of Hydrogel in Drug Delivery 217
5 Hydrogel in Tissue Engineering 219
6 Hydrogels in Wound Healing 221
7 Conclusion 222
Acknowledgements 222
References 223
9 Electrospinning of Hydrogels for Biomedical Applications 226
Abstract 226
1 Introduction 226
2 Overview of Electrospinning 227
2.1 Influence of Process Parameters on Electrospinning 228
2.2 Characteristics of the Solution 229
2.2.1 Concentration 229
2.2.2 Molecular Weight (MW) 229
2.2.3 Viscosity 229
2.2.4 Surface Tension 229
2.2.5 Conductivity/Surface Charge Density 230
2.3 Processing Parameters 230
2.3.1 Voltage 230
2.3.2 Flow Rate 230
2.3.3 Type of Collector 230
2.3.4 Distance Between the Collector and Emitter (Tip) 231
2.4 Ambient Parameters 231
2.5 Theoretical Foundation for Electrospinning Polymers Capable of Physical Gelation 231
3 Applications 233
3.1 Tissue Engineering Applications 233
3.1.1 Choice of Polymer Hydrogel for Tissue Engineering 234
3.1.2 Natural Polymer Hydrogel Nanofibers for Tissue Engineering 234
3.1.3 Synthetic Hydrogels/Polymer for Tissue Engineering 236
3.1.4 Blend of Natural and Synthetic Polymer Nanofibers and Integration of Nanofibers with Hydrogels for Tissue Engineering 238
3.2 Control of Fiber Parameters for Tissue Engineering 240
3.2.1 Control of Fibers for Neural Tissue Engineering 241
3.2.2 Control of Fibers for Vascular Tissue Engineering 242
3.2.3 Control of Fibers for Bone Tissue Engineering 243
3.2.4 Control of Fibers for Ligament and Tendon 243
3.2.5 Control of Fibers for Skin Tissue Engineering 244
3.2.6 Control of Fibers for Cartilage Tissue Engineering 244
3.3 Dressings for Wound Healing 245
3.3.1 Choice of Polymer for Wound Healing 246
3.4 Drug Delivery Applications 246
3.4.1 Methods of Drug Loading unto Electrospun fibers 246
3.4.2 Choice of Polymer/Hydrogels for Nanofibers in Drug Delivery Systems 248
3.4.3 Electrospun Nanofibers that Contain Natural Products for Drug Delivery Systems and Tissue Engineering Applications 249
3.4.4 Electrospun Nanofibers with Drugs for Tissue Engineering Applications 249
3.4.5 Drug-Encapsulated Nanofibers for Wound Recovery 250
4 Recent Strategy Developments in Electrospinning for Drug Delivery 250
4.1 Multilayered Nanofibers 251
4.2 Hollow and Core–Shell Electrospun Fibers 251
4.3 Patterned and Alignment Structures of Nanofibers 253
5 Conclusion and Future Perspective 253
References 254
10 Self-assembling Hydrogels from pH-Responsive Ionic Block Copolymers 266
Abstract 266
1 Introduction 266
2 Gelation Procedure and Association Mechanism 268
3 Theoretical and Simulation Approaches 271
4 Polyelectrolyte-Based Hydrogels 275
4.1 BAB-Type Hydrophobically Associated Polyelectrolytes 276
4.2 Associative Polyelectrolytes of Complex Macromolecular Topologies 280
4.3 Ionogenic pH-Responsive Blocks as Stickers in Associative Gelators 284
4.4 Dual pH/Thermoresponsive Gelators 285
4.5 Effect of Secondary Ionic Interactions on Telechelic Polyelectrolytes 287
5 Hydrogels from Macromolecules Bearing Oppositely Charged Groups 288
5.1 Block Polyampholyte-Based Hydrogels 288
5.2 Random Polyampholyte-Based Hydrogels 291
5.3 Charge-Driven Co-assembling Hydrogels 293
6 Concluding Remarks 297
References 299
11 Cellulose Hydrogels Fabrication, Properties, and Their Application to Biocompatible and Tissue Engineering
Abstract 303
1 Introduction 303
1.1 Hydrogels Made of Hydrophilic Polymers with Crosslinking 303
1.2 Hydrogels Composed of Agro-Waste Cellulose 304
1.3 Biomass Hydrogels for Medical Application 305
1.4 Cellulosic Hydrogels Used as Strategic Biocompatible Materials 306
2 Cellulose Hydrogels in Fabrication and Properties 307
2.1 Conversion Processes of Agro-Industrial Bagasses to Celluloses and then Hydrogels 307
2.2 Fabrication of Cellulose Hydrogel Films by Using Phase Inversion Process 308
2.3 Properties of Cellulosic Hydrogels 309
3 Cellulose Hydrogels in Their Bio and Cytocompatible Applications 311
3.1 Evaluation of the Biocompatibility by In Vivo Test 311
3.2 Cytocompatibility for Tissue Regeneration in Cellulosic Hydrogel Scaffold 313
4 Conclusion and Future Perspective 316
References 316
12 Injectable Hydrogels for Cartilage Regeneration 321
Abstract 321
1 Introduction 322
2 Scaffold Design in Cartilage Tissue Engineering 323
3 Hydrogels Used in Cartilage Repair 324
3.1 Natural Hydrogels 325
3.1.1 Collagen 325
3.1.2 Gelatin 326
3.1.3 Chitosan 327
3.1.4 Hyaluronic Acid 328
3.1.5 Alginate 330
3.1.6 Agarose 330
3.1.7 Native Tissue ECM-Derived Hydrogels 331
3.2 Synthetic Hydrogels 331
3.2.1 Poly(Ethylene Glycol) 332
3.2.2 Poly(Ethylene Glycol Fumarate) 332
3.3 Composite Hydrogels and Hybrids 333
3.4 Multifunctional Hydrogels 336
4 Conclusions and Perspectives 336
Acknowledgements 337
References 337
13 DNA-Based Hydrogels: An Approach for Multifunctional Bioapplications 344
Abstract 344
1 Introduction 345
2 DNA-Based Hydrogels 346
3 Polyethylenimine Coated Surfactant–DNA Gels 349
4 Stimuli-Responsive Polyamine–DNA Nanogels 351
4.1 Delivery of Genes and Anticancer Drugs 353
4.2 Cancer Gene Therapy 356
5 Concluding Remarks 358
References 358
14 Stem Cell Culture on Polymer Hydrogels 362
Abstract 362
1 Introduction 363
2 hHSPCs Expansion on Hydrogels Having Optimal Elasticity 365
2.1 Characterization of PVA Hydrogels Immobilized CS1 and FN 367
2.2 Ex Vivo Expansion of hHSPCs in Nonmodified and Surface-Modified PVA Hydrogels 371
2.3 Analysis of hHSPCs Expanded on Nonmodified and Surface-Modified PVA Hydrogels via Colony-Forming Assays 374
2.4 hHSPC Culture on Hydrogels Having Optimal Elasticity 377
3 Pluripotent Maintenance of HAFSCs on Hydrogels Having Optimal Elasticity 379
3.1 Culture on hAFSCs on Hydrogels Having Optimal Elasticity 379
3.2 The Gene Expression of Pluripotency and Differentiation in hAFSCs Cultured on PVA Hydrogels 382
3.3 The Differentiation and Pluripotency Proteins Expressed on HAFSCs Cultivated on PVA-OligoECM and PVA-ECM Hydrogels 388
3.4 Comparison of the Present Study with Previously Published Studies 390
4 Xeno-Free Culture of HPSCs on Hydrogels with Optimal Elasticity 392
4.1 Cultivation of hESCs and hiPSCs on PVA hydrogels Having Optimal Stiffness 393
4.2 Effect of Surface Density of Biological Cues (OligoVN) on HPSC Proliferation 396
4.3 hPSC Culture for Long Period Under Xeno-Free Culture Conditions 398
4.4 Differentiation of hESCs and hiPSCs Cultured on PVA Hydrogels 400
4.5 Discussion of Cell Culture Materials for hESCs and hiPSCs 403
5 Conclusion and Future Perspective 407
Acknowledgements 408
References 408
15 Various Functional and Stimuli-Responsive Hydrogel Based on Polyaspartamides 414
Abstract 414
1 Synthesis of Poly(Aspartic Acid) and Polyaspartamides 415
2 Hydrogel Based on the Cross-linked PASPs—Superabsorbent Polymer 417
3 Polyaspartamides and the Cross-linked Gel 419
4 Stimuli-Responsive Smart Hydrogels 419
4.1 LCST Solution Behavior and Sol–Gel Transition from Polyaspartamide Copolymers 420
4.2 Thermo-Responsive Polyaspartamides Chemical Gels 422
4.3 Photo-cross-linked Polyaspartamides and the Hybrid Gel with Polysaccharides 423
4.4 pH-Responsive Polyaspartamides Hydrogels 424
4.5 Redox-Responsive Polyaspartamides Hydrogels 425
4.6 CO2-Responsive Polyaspartamides Hydrogels 426
4.7 Multi-responsive Polyaspartamides Hydrogels 426
5 Applications of Smart Polyaspartamide Hydrogels 428
5.1 Hydrogels in Drug Delivery Systems 428
5.2 Injectable Hydrogels for Biomedical Applications 430
5.3 Scaffold for Tissue Engineering 431
5.4 Self-healing Hydrogel 432
6 Conclusion and Future Perspective 433
References 434
16 Hydrogels from Catechol-Conjugated Polymeric Materials 440
Abstract 440
1 Introductory Aspects 440
2 Nature-Related Polymers 443
2.1 Chitosan 443
2.2 Alginate 446
2.3 Hyaluronic Acid 448
2.4 Proteins/Polypeptides 449
3 Synthetic Polymers 451
3.1 Poly(oxyalkylene)s 451
3.2 Polyacrylics 462
3.3 Miscellaneous Polymers 466
4 Conclusion and Future Perspectives 470
References 470