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Biodegradable Thermogels

Biodegradable Thermogels

Xian Jun Loh | David James Young

(2018)

Abstract

Biodegradable thermogels are a promising class of stimuli-responsive polymers. This book summarizes recent developments in thermogel research with a focus on synthesis and self-assembly mechanisms, gel biodegradability, and applications for drug delivery, cell encapsulation and tissue engineering. A closing chapter on commercialisation shows the challenges faced bringing this new material to market.

Edited by leading authorities on the subject, this book offers a comprehensive overview for academics and professionals across polymer science, materials science and biomedical and chemical engineering.


Table of Contents

Section Title Page Action Price
Cover Cover
Preface v
Contents vii
Chapter 1 Thermogelling Polymers and Their History 1
1.1 Introduction 1
1.2 Synthesis 3
1.3 Micellization and Thermogelling Properties 4
1.3.1 Gelation Mechanism 4
1.3.2 Kinetics of Micellization 7
1.3.3 Formation of Micelles with Different Morphologies 7
1.4 Pluronic Systems in the Biomedical Sciences 7
1.4.1 Early Uses 7
1.4.2 Wound Healing 8
1.4.3 Drug Delivery 11
1.5 Disadvantages of Pluronic Systems 13
1.6 Modifications of Pluronic Copolymers 13
1.6.1 Modified Pluronic Copolymers for Improved Mechanical Properties 13
1.6.2 Modified Pluronic Copolymers for Improved Biodegradability 16
1.7 Modern Applications of Pluronics 18
1.8 Future Perspectives 18
References 20
Chapter 2 Thermogelling PLGA-based Copolymers 23
2.1 History and Structures 23
2.2 Synthesis 24
2.3 Properties 25
2.3.1 Reversible Sol-to-gel Transition 25
2.3.2 Degradation 28
2.3.3 Biocompatibility 29
2.4 Applications 30
2.4.1 Drug Release 30
2.4.2 Gene Delivery 37
2.4.3 Postoperative Adhesion Prevention 37
2.5 Areas for Future Research 38
2.6 Conclusions 38
References 39
Chapter 3 Polyester-based Biodegradable Thermogelling Systems as Emerging Materials for Therapeutic Applications 40
3.1 Introduction 40
3.2 Polyester-based Thermogelling Systems 42
3.2.1 The Poly(lactic acid)-based Thermogelling Systems 42
3.2.2 Polycaprolactone-based Thermogelling Systems 45
3.2.3 Poly([R]-3-hydroxybutyrate)-based Thermogelling System 51
3.2.4 Poly(glycerol sebacate)-based Thermogelling Systems 56
3.3 Application of Polyester-based Thermogelling Systems 61
3.3.1 Therapeutic Delivery 61
3.3.2 Tissue Engineering 66
3.4 Conclusion 69
Abbreviations 70
References 71
Chapter 4 Biodegradable Thermogelling Polymers for Drug Delivery 76
4.1 Introduction 76
4.2 Thermogelling Mechanism 77
4.3 Mechanism of Drug Release in Thermogels 78
4.4 Advantages and Disadvantages of Thermogelling Polymeric Materials Compared to Other Drug-delivery Methods 80
4.5 Delivery of Insulin and Protein Drugs in the Treatment of Diabetes 81
4.6 Adaptation of Thermogels for Biomedical Applications 82
4.6.1 Selenium-containing Thermogels 83
4.6.2 Matrix Metalloproteinase-sensitive Thermogelling Polymers 83
4.7 Towards Understanding In-vivo Effectiveness of Polymeric Thermogel Drug Delivery 83
4.7.1 Toxicological Aspects of the Use of Dextran Microspheres and Thermogelling Ethyl(hydroxyethyl) Cellulose as Nasal Drug-delivery Systems 84
4.7.2 In-vivo Pharmacological Evaluations of an Antioxidant-loaded Biodegradable Thermogel 84
4.8 Conclusion 84
References 85
Chapter 5 Injectable Thermogelling Polymers for Bone and Cartilage Tissue Engineering 87
5.1 Introduction 87
5.2 Scaffold Requirements for Bone and Cartilage Tissue Engineering 89
5.3 Chemistry and Properties of Selected Injectable Thermogelling Scaffolds 90
5.3.1 Totally Non-degradable Polymers 90
5.3.2 Enzymatically Degradable Polymers 93
5.3.3 Hydrolytically Degradable Polymers 95
5.4 Conclusions 99
References 100
Chapter 6 Thermogels for Stem Cell Culture 102
6.1 Introduction 102
6.2 Thermogel 3D Scaffolds for Proliferation and Chondrogenic Differentiation of Stem Cells 103
6.3 3D Thermogel Scaffold for Proliferation and Osteogenic Differentiation of Stem Cells 107
6.4 Thermogel 3D Scaffold for Proliferation and Adipogenic Differentiation of Stem Cells 109
6.5 Conclusion 110
References 112
Chapter 7 Degradation Behaviour of Biodegradable Thermogels 113
7.1 Introduction 113
7.2 Relevance of Thermogels 114
7.2.1 Drug Delivery 114
7.2.2 Tissue Engineering 115
7.3 Importance of Degradability 115
7.4 Biodegradation 116
7.4.1 Surface Erosion 116
7.4.2 Bulk Erosion 118
7.4.3 Enzymatic Degradation 119
7.5 In Vivo Degradation 120
7.6 Factors Affecting the Degradation Rate 122
7.6.1 Material Properties 122
7.6.2 Packing of Micelles 122
7.6.3 Bond Type 123
7.6.4 Ratio of Hydrophilic to Hydrophobic Sections 123
7.6.5 Number of Sites for Enzymatic Action 123
7.7 Techniques to Study the Degradable Behaviour of Thermogels 124
7.7.1 Mass Loss 124
7.7.2 Molecular Weight Comparison 124
7.7.3 Surface Topography (Scanning Electron Microscopy) 126
7.7.4 Fourier-transform Infrared Spectroscopy 127
7.7.5 Nuclear Magnetic Resonance Spectroscopy 127
7.7.6 Technique Comparison 129
7.8 Future Perspective 129
References 131
Chapter 8 From Bench to Bedside – OncoGel™, an In Situ Hydrogel for In Vivo Applications 133
8.1 Introduction 133
8.2 Non-clinical Safety and Efficacy Evaluation 134
8.2.1 Safety Studies 135
8.2.2 Tissue Distribution Studies 135
8.3 Development of OncoGel™ as a Potential Cancer Therapeutic Drug 135
8.3.1 Rat Model Studies 135
8.3.2 Pig Model Studies 138
8.3.3 Human Clinical Trials 140
8.4 Perspective 142
References 144
Chapter 9 Hydrogel-based 3D Scaffolds for Stem Cell Culturing and Differentiation 145
9.1 Introduction 145
9.2 Hydrogel-based 3D Culturing and Differentiation of Stem Cells 148
9.3 Hydrogel-based 3D Scaffolds Induce Stem-cell-specific Differentiation 151
9.3.1 Scaffold-induced Neuronal Differentiation 151
9.3.2 Scaffold-induced Hepatogenic Differentiation 151
9.3.3 Scaffold Induced Chondrogenesis Differentiation 153
9.3.4 Scaffold-induced Osteogenic Differentiation 155
9.3.5 Scaffold-induced Adipogenic Differentiation 156
9.4 Conclusion 158
References 159
Chapter 10 Beyond Thermogels – Other Forms of Noncovalently Formed Polymeric Hydrogels 162
10.1 Introduction 162
10.2 Key Features of Noncovalent Polymeric Hydrogels 163
10.3 Types of Noncovalent Polymeric Hydrogels 165
10.3.1 Host–Guest-mediated Supramolecular Hydrogels 165
10.3.2 Noncovalent Hydrogels through Hydrophobic Association 168
10.3.3 Noncovalent Polymeric Hydrogels Through Forming Ionic Bonds 172
10.3.4 Dynamic Covalent Bond-based Polymeric Hydrogels 175
10.4 Summary and Outlook 177
References 178
Subject Index 183