Polyurethane Immobilization of Cells and Biomolecules

T. THOMSON, MS, is Director of Main Street Technologies. He was the founder and Chief Technical Officer of Hydrophilix, Inc., a technology-based firm specializing in the development of advanced medical devices, environmental remediation technologies and consumer products. Mr. Thomson is known for his expertise in the development of products based on hydrophilic polyurethane (HPUR), and his current research includes the application of polyurethane composites to developing scaffolds for cell growth. He wrote 3 books on the subject, holds 7 patents in synthetic chemistry and process control, and has sponsored several seminars on the medical applications of specialty polyurethanes.

Preface ix

1 Polyurethane Chemistry 1

Introduction 1

The Chemistry 2

The Isocyanates 3

The Polyol 5

Cross-Linking 5

The Water Reaction 6

Process 8

The One-Shot Process 8

The Prepolymer Process 10

Post Processing 12

Architecture of Polyurethane Foam 14

Grafting to the Polyurethane Foam 16

Biodegradable PUR 19

Mechanism of Biodegradation 23

More Examples 24

Conclusion 25

References 26

2 Laboratory Practice 29

Introduction 29

Prepolymers 30

Preparation of an Elastomer 30

Preparation of Foam 32

Hydrophobic Foams 32

Hydrophilic Foams 34

Custom Prepolymers, Foams, and Scaffolds 40

Examples 43

Structure–Property Relationships 48

The Special Case of Hydrophilic Polyurethane Foams 50

Physical and Chemical Testing 50

Physical Testing 52

Biocompatibility Testing 54

Process Equipment 54

Metering Pump 55

Mixing Head 55

Tank/Material Retaining Container 55

Machine Manufacturers 56

References 56

3 Scaffolds 59

Introduction 59

Bioscaffolds 61

Examples of Biofilter 65

Elimination of Tobacco Odor from a Cigarette-Manufacturing Plant 67

Treatment of VOCs from an Industrial Plant 68

The Liver as Biofilter 68

Scaffolds for Medical Applications (In Vivo and Extracorporeal) 70

The Liver Model 71

The Extracellular Matrix as Scaffold 72

The Physical Scaffold 73

Design of an Ideal Scaffold 74

Drug Discovery 75

Materials of Construction 77

Ceramics 77

Metals 80

Polymer Scaffolds 82

Poly(lactic Acid) 82

Poly(glycolic Acid) 82

Polycaprolactone 83

Polyurethanes 83

The “Ideal” Scaffold 87

Pore Size and Distribution 89

Void Volume 91

Interconnectedness 96

Surface Area 98

Mechanical Properties 100

Surface Chemistry 100

Specifications

of the Ideal Scaffold 101

References 105

4 Immobilization 109

Introduction 109

Methods of Immobilization 111

Immobilization by Adsorption 113

Biofiltration 113

Biotrickling Filter Setup and Operating Conditions 115

The Toluene Reactor 116

The H2S Reactor 120

Biological Treatment of Aquarium Tanks 123

Protein Adsorption 125

The Avidin–Biotin System 126

Application of the Avidin–Biotin System to Cell Adhesion to a Scaffold 128

Adsorption to a Tricalcium Phosphate (TCP) Scaffold Using the Avidin–Biotin System 128

Hepatic Cells on a Fabricated Polycaprolactone Scaffold 131

Summary of Immobilization by Adsorption 132

Immobilization by Extraction 133

Extraction of Pesticides 138

Summary 144

Immobilization by Entrapment 145

Alginate Encapsulation 146

Encapsulation of Pancreatic Islet Cells 148

Encapsulation of Osteoblasts 148

Introduction to the Pancreas Model 149

The Pancreas Model 150

Summary of Encapsulation 154

Immobilization by Covalent Bonding 154

Overview of Covalent Immobilization 156

Substrates Used for Immobilization 157

Alginates 158

Albumin 159

Collagen 159

Synthetic Polymers as Supports 159

Polyethylene 159

Poly l-Lactic Acid 160

Immobilization to Polyvinyl Chloride 161

Ceramics 163

Summary 163

Polyurethane Immobilization 164

Fundamental Principles 164

Prepolymer Chemistry 168

The Immobilization Chemistry 169

Structure and Chemistry of Biomolecules 170

Preparation of Immobilized Biomolecules 171

Notable Uses of Polyurethane for Immobilization 174

Organophosphates 174

Lipases 177

Fibroblasts 178

Collagen 180

Amyloglucosidase 182

Novel Reactor System 184

Endothelialization 185

Creatinine 186

Conclusion to Immobilization 187

References 189

5 Controlled Release from a Hydrogel Scaffold 195

Introduction 195

Release Rates 198

Examples of Hydrogels Used for Controlled Release 198

Polysaccharides 199

Pectin 199

Alginates 200

Carrageenan 200

Agar 200

Starch 200

Proteins 200

Gelatin 200

Casein 201

Other Proteins 201

Controlled

Release by Diffusion 201

Reservoir Layer 202

Diffusion Experiments 206

Islet Encapsulation 208

Other Controlled Release Examples 211

Targeted Delivery 211

Stomach 212

Small Intestines 212

Colon 212

Summary and Conclusions 213

References 213

Index 215