本书是《Therapeutic Micro/Nano Technology》的影印本，主要讨论了正在兴起的治疗性微米和纳米技术领域。本书所覆盖的主题包括：基于细胞的治疗技术，再生医学——细胞与微米和纳米系统整合(融合)，MEMS与细胞和组织的集成；药物的传递-用于血管内物靶向传递的纳米粒子和非血管系统的药物传递系统(植入性的、口服的、吸入性的)；用于生物界面的分子表面工程，生物分子图案化和细胞图案化。

本书讨论了正在兴起的治疗性微米和纳米技术领域。本书所覆盖的主题包括：基于细胞的治疗技术，再生医学——细胞与微米和纳米系统整合(融合)，MEMS与细胞和组织的集成；药物的传递-用于血管内物靶向传递的纳米粒子和非血管系统的药物传递系统(植入性的、口服的、吸入性的)；用于生物界面的分子表面工程，生物分子图案化和细胞图案化。

本书可供从事纳米科技、材料科学、生物化学和医学的科研人员，高等院校研究生、教学人员参考。

List of Contributors

Foreword

Preface

I.Cell-based Therapeutics

1.Nano-and Micro-Technology to Spatially and Temporally Control

Proteins for Neural Regeneration

Anjana Jain and Ravi V Bellamkonda

1.1 Introduction

  1.1.1 Response after Injury in CNS and PNS

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

1.2 Spatially Controlling Proteins

  1.2.1 Spatial Control: Permissive Bioactive Hydrogel Scaffolds for Enhanced Regeneration

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

  1.2.3 Other Hydrogel Scaffolds

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

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

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

1.3 Temporally Controlling the Release of Proteins

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

  1.3.2 Temporal Control: Slow Release of Trophic Factors Using Microspheres

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

  1.3.4 Temporal Control: Demand Driven Release of Trophic Factors

1.4 Conclusion

  References

2.3-D Fabrication Technology for Tissue Engineering

Alice A.Chen, Valerie Liu Tsang, Dirk Albrecht, and Sangeeta N.Bhatia

2.1 Introduction

2.2 Fabrication of Acellular Constructs

  2.2.1 Heat-Mediated 3D Fabrication

  2.2.2 Light-Mediated Fabrication

  2.2.3 Adhesive-Mediated Fabrication

  2.2.4 Indirect Fabrication by Molding

2.3 Fabrication of Cellular Constructs

2.4 Fabrication of Hybrid Cell/Scaffold Constructs

  2.4.1 Cell-laden Hydrogel Scaffolds by Molding

  2.4.2 Cell-laden Hydrogel Scaffolds by Photopatterning

2.5 Future Directions

  Acknowledgements

  References

3.Designed Self-assembling Peptide Nanobiomaterials

Shuguang Zhang and Xiaojun Zhao

3.1 Introduction 

3.2 Peptide as Biological Material Construction Units

  3.2.1 Lego Peptide

  3.2.2 Surfactant/detergent Peptides

  3.2.3 Molecular Ink Peptides

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

  3.3.1 Ideal Synthetic Biological Scaffolds

  3.3.2 Peptide Scaffolds

  3.3.3 PuraMatrix in vitro Cell Culture Examples

  3.3.4 Extensive Neurite Outgrowth and Active Synapse Formation on PuraMatrix

  3.3.5 Compatible with Bioproduction and Clinical Application

  3.3.6 Synthetic Origin and Clinical-Grade Quality

  3.3.7 Tailor-Made PuraMatrix

3.4 Peptide Surfactants/Detergents Stabilize Membrane Proteins

3.5 Perspective and Remarks

  Acknowledgements

  References

4.At the Interface: Advanced Mierofluidic Assays for Study of Cell Function

Yoko Kamotani, Dongeun Huh, Nobuyuki Futai, and Shuichi Takayama

4.1 Introduction

4.2 Microfabrication 

  4.2.1 Soft Lithography

4.3 Microscale Phenomena

  4.3.1 Scaling Effects

  4.3.2 Laminar Flow

  4.3.3 Surface Tension

4.4 Examples of Advanced Microfluidic Cellular Bioassays

  4.4.1 Patterning with Individual Microfluidic Channels

  4.4.2 Multiple Laminar Streams

  4.4.3 PARTCELL

  4.4.4 Microscale Integrated Sperm Sorter (MISS)

  4.4.5 Air-Sheath Flow Cytometry

  4.4.6 Immunoassays

4.5 Conclusion

  References

5.Multi-phenotypie Cellular Arrays for Biosensing

Laura J.Itle, Won-Gun Koh, and Michael V.Pishko

5.1 Introduction

5.2 Fabrication of Multi-Phenotypic Arrays

  5.2.1 Surface Patterning

  5.2.2 Photolithography

  5.2.3 Soft Lithography

  5.2.4 Poly(ethylene) Glycol Hydrogels

5.3 Detection methods for cell based sensors

  5.3.1 Microelectronics

  5.3.2 Fluorescent Markers For Gene Expression and Protein Up-regulation

  5.3.3 Intracellular Fluorescent Probes for Small Molecules

5.4 Current Examples of Multi-Phenotypic Arrays

5.5 Future Work

  References

6.MEMS and Neurosurgery

Shuvo Roy, Lisa A.Ferrara, Aaron J.Fleischman, and Edward C.BenZel

Part I: Background

6.1 What is Neurosurgery?

6.2 History of Neurosurgery

6.3 Conventional Neurosurgical Treatments

  6.3.1 Hydrocephalus

  6.3.2 Brain Tumors

  6.3.3 Parkinson Disease

  6.3.4 Degenerative Disease of the Spine

6.4 Evolution of Neurosurgery

Part II: Applications

6.5 MEMS for Neurosurgery

6.6 Obstacles to Neurosurgical Employment of MEMS

  6.6.1 Biocompatibility Assessment

6.7 Opportunities

  6.7.1 Intracranial Pressure Monitoring

  6.7.2 Neural Prostheses

  6.7.3 Drug Delivery Systems

  6.7.4 Smart Surgical Instruments and Minimally Invasive Surgery

  6.7.5 In Vivo Spine Biomechanics

  6.7.6 Neural Regeneration

6.8 Prospects for MEMS in Neurosurgery

  Acknowledgements

  References

II.Drug Delivery

7.Vascular Zip Codes and Nanoparticle Targeting

Erkki Ruoslahti

7.1 Introduction

7.2 In vivo Phage Display in Vascular Analysis

7.3 Tissue-Specific Zip Codes in Blood Vessels

7.4 Special Features of Vessels in Disease

7.5 Delivery of Diagnostic and Therapeutic Agents to

   Vascular Targets

7.6 Homing Peptides for Subcellular Targeting

7.7 Nanoparticle Targeting

7.8 Future Directions

   Acknowledgements

   References

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

8.1 Introduction

8.2 Synthesis and Surface Chemistry

  8.2.1 Synthesis of QDs that are Soluble in Organic Solvents

  8.2.2 Modification of Surface Chemistry of QDs for Biological Applications

8.3 Optical Properties

8.4 Applications

  8.4.1 In Vitro Immunoassays & Nanosensors

  8.4.2 Cell Labeling and Tracking Experiments

  8.4.3 In Vivo Live Animal Imaging

8.5 Future Work 

  Acknowledgements

  References

9.Diagnostic and Therapeutic Applications of Metal Nanoshells

Leon R.Hirseh, Rebekah A.Drezek, Naomi J.Halas, and Jennifer L.West

9.1 Metal Nanoshells

9.2 Biomedical Applications of Gold Nanoshells

  9.2.1 Nanoshells for Immunoassays

  9.2.2 Photothermally-modulated Drug Delivery Using Nanoshell-Hydrogel Composites

  9.2.3 Photothermal Ablation

  9.2.4 Nanoshells for Molecular Imaging

  References

10.Nanoporous Microsystems for Islet Cell Replacement

Tejal A.Desai, Teri West, Michael Cohen, Tony Boiarski, and

Arfaan Rampersaud

10.1 Introduction

  10.1.1 The Science of Miniaturization (MEMS and BioMEMS)

  10.1.2 Cellular Delivery and Encapsulation

  10.1.3 Microfabricated Nanoporous Biocapsule

10.2 Fabrication of Nanoporous Membranes

10.3 Biocapsule Assembly and Loading

10.4 Biocompatibility of Nanoporous Membranes and Biocapsular Environment

10.5 Microfabricated Biocapsule Membrane Diffusion Studies

  10.5.1 IgG Diffusion

10.6 Matrix Materials Inside the Biocapsule

  10.6.1 In-Vivo Studies

  10.6.2 Histology

  Conclusion

  Acknowledgements

  References

11.Medical Nanotechnology and Pulmonary Pathology

Amy Pope-Harman and Mauro Ferrari

11.1 Introduction 

  11.1.1 Today's Medical Environment

  11.1.2 Challenges for Pulmonary Disease-Directed Nanotechnology Devices

11.2 Current Applications of Medical Technology in the Lungs

  11.2.1 Molecularly-derived Therapeutics

  11.2.2 Liposomes

  11.2.3 Devices with Nanometer-scale Features

11.3 Potential uses of Nanotechnology in Pulmonary Diseases

  11.3.1 Diagnostics

  11.3.2 Therapeutics

  11.3.3 Evolving Nanotechnology in Pulmonary Diseases 

11.4 Conclusion

  References

12.Nanodesigned Pore-Containing Systems for Biosensing and Controlled Drug Release

Frederique Cunin, Yang Yang Li, and Michael J.Sailor

12.1 System Design Considerations

12.2 Porous Material-Based Systems

12.3 Silicon-Based Porous Materials

12.4 "Obedient" Materials

12.5 Porous Silicon

12.6 Templated Nanomaterials

12.7 Photonic Crystals as Self-Reporting Biomaterials

12.8 Using Porous Si as a Template for Optical Nanostructures

12.9 Outlook for Nanotechnology in Pharmaceutical Research

  Acknowledgements

  References

13.Transdermal Drug Delivery using Low-Frequency Sonophoresis

Samir Mitragotri

13.1 Introduction

  13.1.1 Avoiding Drag Degradation in Gastrointestinal Tract

  13.1.2 Better Patient Compliance

  13.1.3 Sustained Release of the Drug can be Obtained

13.2 Ultrasound in Medical Applications

13.3 Sonophoresis: Ultrasound-Mediated Transdermal Transport

13.4 Low-Frequency Sonophoresis

13.5 Low-Frequency Sonophoresis: Choice of Parameters

13.6 Macromolecular Delivery

  13.6.1 Peptides and Proteins

  13.6.2 Low-molecular Weight Heparin

  13.6.30ligonucleotides

  13.6.4 Vaccines

13.7 Transdermal Glucose Extraction Using Sonophoresis

13.8 Mechanisms of Low-Frequency Sonophoresis

13.9 Conclusions

  References

14.Microdevices for Oral Drug Delivery

Sarah L.Tao and Tejal A.Desai

14.1 Introduction

  14.1.1 Current Challenges in Drug Delivery

  14.1.2 Oral Drug Delivery

  14.1.3 Bioadhesion in the Gastrointestinal Tract

  14.1.4 Microdevice Technology

14.2 Materials

  14.2.1 Silicon Dioxide

  14.2.2 Porous Silicon

  14.2.3 Poly(methyl methacrylate)

14.3 Microfabrication

  14.3.1 Silicon Dioxide

  14.3.2 Porous Silicon

  14.3.3 Pol(methyl methacrylate)

14.4 Surface Chemistry

  14.4.1 Aimine Functionalization

  14.4.2 Avidin Immobilization

  14.4.3 Lectin Conjugation

14.5 Surface Characterization

14.6 Miocrodevice Loading and Release Mechanisms

  14.6.1 Welled Silicon Dioxide and PMMA Microdevices

  14.6.2 Porous Silicon Microdevices

  14.6.3 CACO-2 In Vitro Studies

  14.6.4 Cell Culture Conditions

  14.6.5 Assessing Confluency and Tight Junction Formation

  14.6.6 Adhesion ofLectin-Modified Microdevices

  14.6.7 Bioavailibility Studies

  Acknowledgements

  References

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

15.1 Introduction

  15.1.I Concept of Controlled Drug Delivery

  15.1.2 Nanopore Technology

  15.1.3 Comparison of Nanopore Technology with Existing Drug Delivery Technologies

15.2 Fabrication of Nanoporous Membranes

15.3 Implant Assembly and Loading

15.4 Nanoporous Implant Diffusion Studies

  15.4.1 Interferon Release Data

  15.4.2 Bovine Serum Albumin Release Data

  15.4.3 Results Interpretation

  15.4.4 Modeling and Data Fitting

15.5 Biocompatibility of Nanoporous Implants

  15.5.1 In Vivo Biocompatibility Evaluation

  15.5.2 Long-Term Lysozyme Diffusion Studies

  15.5.3 In Vivo/In Vitro Correlation

  15.5.4 Post-Implant Diffusion Data

15.6 Conclusions

  References

III.Molecular Surface Engineering for the Biological Interface

16.Micro and Nanoscale Smart Polymer Technologies in Biomedicine

Samarth Kulkarni, Noah Malmstadt, Allan S.Hoffman, and Patrick S.Stayton

16.1 Smart Polymers

  16.1.1 Mechanism of Aggregation

16.2 Smart Meso-Scale Particle Systems

  16.2.1 Introduction

  16.2.2 Preparation of PNIPAAm-Streptavidin Particle System

  16.2.3 Mechanism of Aggregation

  16.2.4 Properties of PNIPAAm-Streptavidin Particle System

  16.2.5 Protein Switching in Solution using AggregationSwitch

  16.2.6 Potential uses of Smart P01ymer Particles in Diagnostics and Therapy

16.3 Smart Bead Based Microfiuidic Chromatography

  16.3.1 Introduction

  16.3.2 Preparation of Smart Beads

  16.3.3 Microfluidic Devices for Bioanalysis

  16.3.4 Microfluidic Affinity Chromatography Using Smart Beads

  16.3.5 Microfluidic Immunoassay Using Smart Beads

  16.3.6 Smart Polymer Based MicrotechnologyFuture Outlook

  Acknowledgements

  References

17.Supported Lipid Bilayers asMimics for Cell Surfaces

Jay T.Groves

17.1 IntrOduction

17.2 Physical Characteristics

17.3 Fabrication Methodologies

17.4 Applications

  17.4.1 Membrane Arrays

  17.4.2 Membrane-Coated Beads.

  17.4.3 Electrical Manipulation

  17.4.4 Live Cell Interactions

17.5 Conclusion

  References

18.Engineering Cell Adhesion 

Kiran Bhadriraju, Wendy Liu, Darren Gray, and Christopher S.Chen

18.1 Introduction

18.2 Regulating Cell Function via the Adhesive Microenvironment

18.3 Controlling Cell Interactions with the Surrounding Environment

  18.3.1 Creating Defined Surface Chemistries

  18.3.2 The Development of Surface Patterning

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

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

18.4 Future Work

  18.4.1 Developing New Materials

  18.4.2 Better Cell Positioning Technologies

  18.4.3 Patterning in 3D Environments

  18.4.4 Patterning Substrate Mechanics

18.5 Conclusions

  References

19.Cell Biology on a Chip

Albert Folch and Anna Tourovskaia

19.1 Introduction

19.2 The Lab-on-a-chip Revolution

19.3 Increasing Experimentation Throughput

  19.3.1 From Serial Pipetting to Highly Parallel Micromixers

  19.3.2 From Incubators to "Chip-Cubators"

  19.3.3 From High Cell Numbers in Large Volumes (and Large Areas) to Low Cell Numbers in Small Volumes (and Small Areas)

  19.3.4 From Milliliters to Microliters or Nanoliters

  19.3.5 From Manual/Robotic Pipetting to Microfluidic Pumps and Valves

  19.3.6 Single-Cell Probing and Manipulation

19.4 Increasing the Complexity of the Cellular Microenvironment

  19.4.1 From Random Cultures to Microengineered Substrates

  19.4.2 From "Classical" to "Novel" Substrates

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

  19.4.4 From a Homogeneous Bath to Microfluidic Delivery of Biochemical Factors

19.5 Conclusion

  References

About the Editors

Index