面向医学治疗的微纳米技术 英文PDF电子书下载

Ⅰ．Cell-based Therapeutics 1

1．Nano-and Micro-Technology to Spatially and Temporally Control Proteins for Neural Regeneration&Anjana Jain and Ravi V.Bellamkonda 3

1.1 Introduction 3

1.1.1 Response after Injury in CNS and PNS 4

1.1.2 Nano-and Micro-scale Strategies to Promote Axonal Outgrowth in the CNS and PNS 4

1.2 Spatially Controlling Proteins 6

1.2.1 Spatial Control:Permissive Bioactive Hydrogel Scaffolds for Enhanced Regeneration 7

1.2.2 Spatial Control:Chemical vs.Photochemical Crosslinkers for Immobilization of Bioactive Agents 8

1.2.3 Other Hydrogel Scaffolds 10

1.2.4 Spatial Control:Contact Guidance as a Strategy to Promote Regeneration 10

1.2.5 Spatial Control:Nerve Guide Conduits Provide an Environment for Axonal Regeneration 11

1.2.6 Spatial Control:Cell-scaffold Constructs as a Way of Combining Permissive Substrates with Stimuli for Regeneration 12

1.3 Temporally Controlling the Release of Proteins 13

1.3.1 Temporal Control:Osmotic Pumps Release Protein to Encourage Axonal Outgrowth 14

1.3.2 Temporal Control:Slow Release of Trophic Factors Using Microspheres 15

1.3.3 Temporal Control:Lipid Microtubules for Sustained Release of Stimulatory Trophic Factors 16

1.3.4 Temporal Control:Demand Driven Release of Trophic Factors 17

1.4 Conclusion 17

References 18

2．3-D Fabrication Technology for Tissue Engineering&Alice A.Chen,Valerie Liu Tsang,Dirk Albrecht,and Sangeeta N.Bhatia 23

2.1 Introduction 23

2.2 Fabrication of Acellular Constructs 24

2.2.1 Heat-Mediated 3D Fabrication 24

2.2.2 Light-Mediated Fabrication 27

2.2.3 Adhesive-Mediated Fabrication 28

2.2.4 Indirect Fabrication by Molding 29

2.3 Fabrication of Cellular Constructs 30

2.4 Fabrication of Hybrid Cell/Scaffold Constructs 31

2.4.1 Cell-laden Hydrogel Scaffolds by Molding 31

2.4.2 Cell-laden Hydrogel Scaffolds by Photopatterning 32

2.5 Future Directions 34

Acknowledgements 36

References 36

3．Designed Self-assembling Peptide Nanobiomaterials&Shuguang Zhang and Xiaojun Zhao 39

3.1 Introduction 40

3.2 Peptide as Biological Material Construction Units 40

3.2.1 Lego Peptide 41

3.2.2 Surfactant/detergent Peptides 42

3.2.3 Molecular Ink Peptides 45

3.3 Peptide Nanofiber Scaffold for 3-D Cell Culture,Tissue Engineering and Regenerative Medicine 47

3.3.1 Ideal Synthetic Biological Scaffolds 47

3.3.2 Peptide Scaffolds 48

3.3.3 PuraMatrix in vitro Cell Culture Examples 49

3.3.4 Extensive Neurite Outgrowth and Active Synapse Formation on PuraMatrix 50

3.3.5 Compatible with Bioproduction and Clinical Application 51

3.3.6 Synthetic Origin and Clinical-Grade Quality 51

3.3.7 Tailor-Made PuraMatrix 51

3.4 Peptide Surfactants/Detergents Stabilize Membrane Proteins 52

3.5 Perspective and Remarks 52

Acknowledgements 53

References 53

4．At the Interface:Advanced Microfluidic Assays for Study of Cell Function&Yoko Kamotani,Dongeun Huh,Nobuyuki Futai,and Shuichi Takayama 55

4.1 Introduction 55

4.2 Microfabrication 56

4.2.1 Soft Lithography 57

4.3 Microscale Phenomena 58

4.3.1 Scaling Effects 59

4.3.2 Laminar Flow 59

4.3.3 Surface Tension 60

4.4 Examples of Advanced Microfluidic Cellular Bioassays 61

4.4.1 Patterning with Individual Microfluidic Channels 61

4.4.2 Multiple Laminar Streams 63

4.4.3 PARTCELL 66

4.4.4 Microscale Integrated Sperm Sorter(MISS) 68

4.4.5 Air-Sheath Flow Cytometry 69

4.4.6 Immunoassays 71

4.5 Conclusion 75

References 75

5．Multi-phenotypic Cellular Arrays for Biosensing&Laura J.Itle,Won-Gun Koh,and Michael V.Pishko 79

5.1 Introduction 79

5.2 Fabrication of Multi-Phenotypic Arrays 81

5.2.1 Surface Patterning 81

5.2.2 Photolithography 81

5.2.3 Soft Lithography 82

5.2.4 Poly(ethylene) Glycol Hydrogels 83

5.3 Detection methods for cell based sensors 84

5.3.1 Microelectronics 84

5.3.2 Fluorescent Markers For Gene Expression and Protein Up-regulation 84

5.3.3 Intracellular Fluorescent Probes for Small Molecules 86

5.4 Current Examples of Multi-Phenotypic Arrays 87

5.5 Future Work 88

References 90

6．MEMS and Neurosurgery&Shuvo Roy,Lisa A.Ferrara,Aaron J.Fleischman,and Edward C.Benzel 95

Part Ⅰ:Background 95

6.1 What is Neurosurgery？ 95

6.2 History of Neurosurgery 95

6.3 Conventional Neurosurgical Treatments 99

6.3.1 Hydrocephalus 99

6.3.2 Brain Tumors 101

6.3.3 Parkinson Disease 103

6.3.4 Degenerative Disease of the Spine 104

6.4 Evolution of Neurosurgery 106

Part Ⅱ:Applications 107

6.5 MEMS for Neurosurgery 107

6.6 Obstacles to Neurosurgical Employment of MEMS 108

6.6.1 Biocompatibility Assessment 109

6.7 Opportunities 110

6.7.1 Intracranial Pressure Monitoring 110

6.7.2 Neural Prostheses 112

6.7.3 Drug Delivery Systems 113

6.7.4 Smart Surgical Instruments and Minimally Invasive Surgery 114

6.7.5 In Vivo Spine Biomechanics 116

6.7.6 Neural Regeneration 118

6.8 Prospects for MEMS in Neurosurgery 120

Acknowledgements 120

References 120

Ⅱ．Drug Delivery 125

7．Vascular Zip Codes and Nanoparticle Targeting&Erkki Ruoslahti 127

7.1 Introduction 127

7.2 In vivo Phage Display in Vascular Analysis 128

7.3 Tissue-Specific Zip Codes in Blood Vessels 128

7.4 Special Features of Vessels in Disease 129

7.5 Delivery of Diagnostic and Therapeutic Agents to Vascular Targets 131

7.6 Homing Peptides for Subcellular Targeting 131

7.7 Nanoparticle Targeting 132

7.8 Future Directions 133

Acknowledgements 134

References 134

8．Engineering Biocompatible Quantum Dots for Ultrasensitive,Real-Time Biological Imaging and Detection&Wen Jiang,Anupam Singhal,Hans Fischer,Sawitri Mardyani,and Warren C.W.Chan 137

8.1 Introduction 137

8.2 Synthesis and Surface Chemistry 138

8.2.1 Synthesis of QDs that are Soluble in Organic Solvents 138

8.2.2 Modification of Surface Chemistry of QDs for Biological Applications 141

8.3 Optical Properties 142

8.4 Applications 146

8.4.1 In Vitro Immunoassays ＆ Nanosensors 146

8.4.2 Cell Labeling and Tracking Experiments 149

8.4.3 In Vivo Live Animal Imaging 150

8.5 Future Work 152

Acknowledgements 152

References 152

9．Diagnostic and Therapeutic Applications of Metal Nanoshells&Leon R.Hirsch,Rebekah A.Drezek,Naomi J.Halas,and Jennifer L.West 157

9.1 Metal Nanoshells 157

9.2 Biomedical Applications of Gold Nanoshells 161

9.2.1 Nanoshells for Immunoassays 161

9.2.2 Photothermally-modulated Drug Delivery Using Nanoshell-Hydrogel Composites 162

9.2.3 Photothermal Ablation 165

9.2.4 Nanoshells for Molecular Imaging 166

References 168

10．Nanoporous Microsystems for Islet Cell Replacement&Tejal A.Desai,Teri West,Michael Cohen,Tony Boiarski,and Arfaan Rampersaud 171

10.1 Introduction 171

10.1.1 The Science of Miniaturization(MEMS and BioMEMS) 171

10.1.2 Cellular Delivery and Encapsulation 172

10.1.3 Microfabricated Nanoporous Biocapsule 174

10.2 Fabrication of Nanoporous Membranes 175

10.3 Biocapsule Assembly and Loading 178

10.4 Biocompatibility of Nanoporous Membranes and Biocapsular Environment 179

10.5 Microfabricated Biocapsule Membrane Diffusion Studies 181

10.5.1 IgG Diffusion 183

10.6 Matrix Materials Inside the Biocapsule 185

10.6.1 In-Vivo Studies 187

10.6.2 Histology 188

Conclusion 189

Acknowledgements 189

References 189

11．Medical Nanotechnology and Pulmonary Pathology&Amy Pope-Harman and Mauro Ferrari 193

11.1 Introduction 193

11.1.1 Today's Medical Environment 194

11.1.2 Challenges for Pulmonary Disease-Directed Nanotechnology Devices 195

11.2 Current Applications of Medical Technology in the Lungs 196

11.2.1 Molecularly-derived Therapeutics 196

11.2.2 Liposomes 197

11.2.3 Devices with Nanometer-scale Features 198

11.3 Potential uses of Nanotechnology in Pulmonary Diseases 198

11.3.1 Diagnostics 198

11.3.2 Therapeutics 200

11.3.3 Evolving Nanotechnology in Pulmonary Diseases 203

11.4 Conclusion 207

References 208

12．Nanodesigned Pore-Containing Systems for Biosensing and Controlled Drug Release&Frédérique Cunin,Yang Yang Li,and Michael J.Sailor 213

12.1 System Design Considerations 214

12.2 Porous Material-Based Systems 214

12.3 Silicon-Based Porous Materials 215

12.4 "Obedient"Materials 216

12.5 Porous Silicon 216

12.6 Templated Nanomaterials 217

12.7 Photonic Crystals as Self-Reporting Biomaterials 217

12.8 Using Porous Si as a Template for Optical Nanostructures 217

12.9 Outlook for Nanotechnology in Pharmaceutical Research 219

Acknowledgements 219

References 220

13．Transdermal Drug Delivery using Low-Frequency Sonophoresis&Samir Mitragotri 223

13.1 Introduction 223

13.1.1 Avoiding Drug Degradation in Gastrointestinal Tract 223

13.1.2 Better Patient Compliance 223

13.1.3 Sustained Release of the Drug can be Obtained 224

13.2 Ultrasound in Medical Applications 224

13.3 Sonophoresis:Ultrasound-Mediated Transdermal Transport 224

13.4 Low-Frequency Sonophoresis 225

13.5 Low-Frequency Sonophoresis:Choice of Parameters 226

13.6 Macromolecular Delivery 226

13.6.1 Peptides and Proteins 226

13.6.2 Low-molecular Weight Heparin 227

13.6.3 Oligonucleotides 228

13.6.4 Vaccines 228

13.7 Transdermal Glucose Extraction Using Sonophoresis 229

13.8 Mechanisms of Low-Frequency Sonophoresis 230

13.9 Conclusions 232

References 232

14．Microdevices for Oral Drug Delivery&Sarah L.Tao and Tejal A.Desai 237

14.1 Introduction 237

14.1.1 Current Challenges in Drug Delivery 237

14.1.2 Oral Drug Delivery 238

14.1.3 Bioadhesion in the Gastrointestinal Tract 238

14.1.4 Microdevice Technology 240

14.2 Materials 241

14.2.1 Silicon Dioxide 242

14.2.2 Porous Silicon 242

14.2.3 Poly(methyl methacrylate) 242

14.3 Microfabrication 243

14.3.1 Silicon Dioxide[23] 243

14.3.2 Porous Silicon[25] 244

14.3.3 Pol(methyl methacrylate)[24] 246

14.4 Surface Chemistry 247

14.4.1 Aimine Functionalization 249

14.4.2 Avidin Immobilization 251

14.4.3 Lectin Conjugation 251

14.5 Surface Characterization 251

14.6 Miocrodevice Loading and Release Mechanisms 253

14.6.1 Welled Silicon Dioxide and PMMA Microdevices 254

14.6.2 Porous Silicon Microdevices 254

14.6.3 CACO-2 In Vitro Studies 255

14.6.4 Cell Culture Conditions 255

14.6.5 Assessing Confluency and Tight Junction Formation 256

14.6.6 Adhesion of Lectin-Modified Microdeviees 256

14.6.7 Bioavailibility Studies 257

Acknowledgements 258

References 259

15．Nanoporous Implants for Controlled Drug Delivery&Tejal A.Desai,Sadhana Sharma,Robbie J.Walczak,Anthony Boiarski,Michael Cohen,John Shapiro,Teri West,Kristie Melnik,Carlo Cosentino,Piyush M.Sinha,and Mauro Ferrari 263

15.1 Introduction 263

15.1.1 Concept of Controlled Drug Delivery 263

15.1.2 Nanopore Technology 264

15.1.3 Comparison of Nanopore Technology with Existing Drug Delivery Technologies 267

15.2 Fabrication of Nanoporous Membranes 269

15.3 Implant Assembly and Loading 271

15.4 Nanoporous Implant Diffusion Studies 271

15.4.1 Interferon Release Data 272

15.4.2 Bovine Serum Albumin Release Data 273

15.4.3 Results Interpretation 275

15.4.4 Modeling and Data Fitting 276

15.5 Biocompatibility of Nanoporous Implants 277

15.5.1 In Vivo Biocompatibility Evaluation 278

15.5.2 Long-Term Lysozyme Diffusion Studies 279

15.5.3 In Vivo/In Vitro Correlation 281

15.5.4 Post-Implant Diffusion Data 282

15.6 Conclusions 283

References 283

Ⅲ．Molecular Surface Engineering for the Biological Interface 287

16．Micro and Nanoscale Smart Polymer Technologies in Biomedicine&Samarth Kulkarni,Noah Malmstadt,Allan S.Hoffman,and Patrick S.Stayton 289

16.1 Smart Polymers 290

16.1.1 Mechanism of Aggregation 290

16.2 Smart Meso-Scale Particle Systems 291

16.2.1 Introduction 291

16.2.2 Preparation of PNIPAAm-Streptavidin Particle System 293

16.2.3 Mechanism of Aggregation 293

16.2.4 Properties of PNIPAAm-Streptavidin Particle System 293

16.2.5 Protein Switching in Solution using Aggregation Switch 294

16.2.6 Potential uses of Smart Polymer Particles in Diagnostics and Therapy 296

16.3 Smart Bead Based Microfluidic Chromatography 296

16.3.1 Introduction 296

16.3.2 Preparation of Smart Beads 297

16.3.3 Microfluidic Devices for Bioanalysis 298

16.3.4 Microfluidic Affinity Chromatography Using Smart Beads 298

16.3.5 Microfluidic Immunoassay Using SmartBeads 301

16.3.6 Smart Polymer Based Microtechnology—Future Outlook 301

Acknowledgements 301

References 302

17．Supported Lipid Bilayers as Mimics for Cell Surfaces&Jay T.Groves 305

17.1 Introduction 305

17.2 Physical Characteristics 306

17.3 Fabrication Methodologies 310

17.4 Applications 313

17.4.1 Membrane Arrays 313

17.4.2 Membrane-Coated Beads 314

17.4.3 Electrical Manipulation 316

17.4.4 Live Cell Interactions 317

17.5 Conclusion 319

References 320

18．Engineering Cell Adhesion&Kiran Bhadriraju,Wendy Liu,Darren Gray,and Christopher S.Chen 325

18.1 Introduction 325

18.2 Regulating Cell Function via the Adhesive Microenvironment 327

18.3 Controlling Cell Interactions with the Surrounding Environment 330

18.3.1 Creating Defined Surface Chemistries 330

18.3.2 The Development of Surface Patterning 332

18.3.3 Examples of Patterning-Based Studies on Cell-To-Cell Interactions 333

18.3.4 Examples of Patterning-Based Studies on Cell-Matrix Interactions 336

18.4 Future Work 337

18.4.1 Developing New Materials 337

18.4.2 Better Cell Positioning Technologies 338

18.4.3 Patterning in 3D Environments 338

18.4.4 Patterning Substrate Mechanics 339

18.5 Conclusions 339

References 340

19．Cell Biology on a Chip&Albert Folch and Anna Tourovskaia 345

19.1 Introduction 345

19.2 The Lab-on-a-chip Revolution 346

19.3 Increasing Experimentation Throughput 347

19.3.1 From Serial Pipetting to Highly Parallel Micromixers 347

19.3.2 From Incubators to"Chip-Cubators" 349

19.3-3 From High Cell Numbers in Large Volumes(and Large Areas)to Low Cell Numbers in Small Volumes(and Small Areas) 349

19.3.4 From Milliliters to Microliters or Nanoliters 350

19.3.5 From Manual/Robotic Pipetting to Microfluidic Pumps and Valves 351

19.3.6 Single-Cell Probing and Manipulation 354

19.4 Increasing the Complexity of the Cellular Microenvironment 354

19.4.1 From Random Cultures to Microengineered Substrates 355

19.4.2 From"Classical"to"Novel"Substrates 356

19.4.3 From Cells in Large Static Volumes to Cells in Small Flowing Volumes 359

19.4.4 From a Homogeneous Bath to Microfluidic Delivery of Biochemical Factors 359

19.5 Conclusion 360

References 360

About the Editors 365

Index 367