Table of Contents
2123fm.pdf
Tissue Engineering and Artificial Organs, Third Edition
Introduction and Preface
Evolution of the Modern Health Care System
Biomedical Engineering: A Definition
Activities of Biomedical Engineers
Editor-in-Chief
Contributors
Contents
2123ch1.pdf
Table of Contents
SECTION I: Molecular Biology
Chapter 1: Historical Perspective and Basics of Molecular Biology
1.1 Introduction
1.2 Molecular Biology: A Historical Perspective
1.3 The Central Dogma of Modern Molecular Biology
1.3.1 DNA Base Composition, Connectivity, and Structure
1.3.2 Base Sequence, Information, and Genes
1.3.3 Codon Information to a Protein
1.3.4 DNA Replication
1.3.5 mRNA Dynamics
1.3.6 Variations and Refinements of the Central Dogma
1.4 Molecular Biology Leads to a Refined Classification of Cells
1.5 Mutations
1.6 Nucleic Acid Processing Mechanisms and Inspired Technologies with Medical and Other Impacts
1.6.1 Nucleic Acid Modification Enzymes
1.6.2 Copying DNA in the Laboratory
1.6.3 Basic Bacterial Transformation Techniques
1.6.4 Transfecting Eucaryotic Cells
1.7 Computerized Storage and Use of DNA Sequence Information
1.8 Probing Gene Expression
1.8.1 DNA Microarrays Profile Many Gene Expression Events
References and Recommended Further Reading
Backgrounds on Some Molecular Biology Pioneers
Data Bases and Other Supplementary Materials on Basic Molecular Biology
More Information and Archives Regarding DNA Arrays
2123ch2.pdf
Table of Contents
Chapter 2: Systems and Technology Involving Bacteria
2.1 Introduction
2.2 Elements for Expression
2.3 A Cell-to-Cell Communications Operon
2.4 Marker Proteins
2.5 Growth of Bacterial Cultures
2.6 Regulons
2.7 Engineering the System
References
2123ch3.pdf
Table of Contents
Chapter 3: Recombinant DNA Technology Using Mammalian Cells
3.1 Expression in Mammalian Cells
3.1.1 Introduction
3.1.2 Vector Design
3.1.3 Inducible Systems
3.1.4 Cell Lines
3.1.5 Transfection Methods
3.1.6 Transient vs. Stable Transfection
3.1.7 Selectable Markers
3.1.8 Single Cell Cloning Methods
References
2123ch4.pdf
Table of Contents
SECTION II: Transport Phenomena and Biomimetic Systems
References
Chapter 4: Biomimetic Systems
4.1 Concepts of Biomimicry
4.1.1 Morphology and Properties Development
4.1.2 Molecular Engineering of Thin Films and Nanocapsules
4.1.3 Biotechnology, Bioreaction Engineering, and Systems Development
4.2 Biomimicry and Tissue Engineering
4.2.1 Integrated Systems
4.2.2 Blood Brain Barrier
4.2.3 Vascular System
4.2.4 Implants
4.3 Biomimetic Membranes for Ion Transport
4.3.1 Active Transport Biomimetics
4.3.2 Mechanism for Facilitated Diffusion in Fixed-Carrier Membranes
4.3.3 Jumping Mechanism in Immobilized Liquid Membranes
4.4 Assessing Mass Transfer Resistances in Biomimetic Reactors
4.4.1 Uncoupling Resistances
4.4.2 Use in Physiologically Based Pharmacokinetics Models and Cell Culture Analog Systems
4.5 Electroenzymatic Membrane Reactors as Electron Transfer Chain Biomimetics
4.5.1 Mimicry of In Vivo Coenzyme Regeneration Processes
4.5.2 Electroenzymatic Production of Lactate from Pyruvate
References
2123ch5.pdf
Table of Contents
Chapter 5: Diffusional Processes and Engineering Design
5.1 Applications of Allometry
5.2 Flow Limited Processes
5.3 Extracorporeal Systems
5.3.1 Membrane Separators
5.3.2 Chromatographic Columns
5.3.3 Flow Reactors
5.4 Useful Correlations
5.4.1 Convective Mass Transfer
5.4.2 Convective Dispersion and the One-Dimensional Convective Diffusion Equation
References
2123ch6.pdf
Table of Contents
Chapter 6: Microvascular Heat Transfer
6.1 Introduction and Conceptual Challenges
6.2 Basic Concepts
6.3 Heat Transfer to Blood Vessels
6.3.1 Vascular Models
6.3.2 Equilibration Lengths
6.3.3 Countercurrent Heat Exchange
6.3.4 Heat Transfer Inside of a Blood Vessel
6.4 Models of Perfused Tissues
6.4.1 Continuum Models
6.4.1.1 Formulations
6.4.1.2 Combination
6.4.2 Multi-Equation Models
6.4.3 Vascular Reconstruction Models
6.5 Parameter Values
6.5.1 Thermal Properties
6.5.2 Thermoregulation
6.5.3 Clinical Heat Generation
6.6 Solutions of Models
Defining Terms
References
2123ch7.pdf
Table of Contents
Chapter 7: Perfusion Effects and Hydrodynamics
7.1 Introduction
7.2 Elements of Theoretical Hydrodynamics
7.2.1 Elements of Continuum Mechanics
7.2.1.1 Constitutive Equations
7.2.1.2 Conservation (Field) Equations
7.2.1.3 Turbulence and Instabilities
7.2.2 Flow in Tubes
7.2.2.1 Steady Poiseuille Flow
7.2.2.2 Entrance Flow
7.2.2.3 Mechanical Energy Equation
7.3 Pulsatile Flow
7.3.1 Hemodynamics in Rigid Tubes: Womersley’s Theory
7.3.2 Hemodynamics in Elastic Tubes
7.3.3 Turbulence in Pulsatile Flow
7.4 Models and Computational Techniques
7.4.1 Approximations to the Navier–Stokes Equations
7.4.2 Computational Fluid Dynamics
References
2123ch8.pdf
Table of Contents
Chapter 8: Animal Surrogate Systems
8.1 Background
8.1.1 Limitations of Animal Studies
8.1.2 Alternatives to Animal Studies
8.2 The Cell Culture Analog Concept
8.3 Prototype CCA
8.4 Use of Engineered Tissues or Cells for Toxicity/Pharmacology
8.5 Future Prospects
Defining Terms
References
2123ch9.pdf
Table of Contents
Chapter 9: Arterial Wall Mass Transport: The Possible Role of Blood Phase Resistance in the Localization of Arterial Disease
9.1 Steady-State Transport Modeling
9.1.1 Reactive Surface
9.1.2 Permeable Surface
9.1.3 Reactive Wall
9.2 Damkhöler Numbers for Important Solutes
9.2.1 Adenosine Triphosphate
9.2.2 Albumin and LDL
9.2.3 Oxygen
9.3 Sherwood Numbers in the Circulation
9.3.1 Straight Vessels
9.4 Nonuniform Geometries Associated with Atherogenesis
9.4.1 Sudden Expansion
9.4.2 Stenosis
9.4.3 Bifurcation
9.4.4 Curvature
9.5 Discussion
9.6 Possible Role of Blood Phase Transport in Atherogenesis
9.6.1 Direct Mechanical Effects on Endothelial Cells
9.6.2 Hypoxic Effect on Endothelial Cells
9.6.3 Hypoxia Induces VEGF
References
2123ch10.pdf
Table of Contents
Chapter 10: Control of the Microenvironment
10.1 Introduction
10.2 Tissue Microenvironments
10.2.1 Specifying Performance Criteria
10.2.2 Estimating Tissue Function
10.2.2.1 Blood
10.2.2.2 Bone Marrow Microenvironment
10.2.3 Communication
10.2.3.1 Cellular Communication Within Tissues
10.2.3.2 Soluble Growth Factors
10.2.3.3 Direct Cell-to-Cell Contact
10.2.3.4 Extracellular Matrix and Cell–Tissue Interactions
10.2.3.5 Communication with the Whole Body Environment
10.2.4 Cellularity
10.2.5 Dynamics
10.2.6 Geometry
10.2.7 System Interactions: Reaction and Transport Processes
10.3 Reacting Systems and Bioreactors
10.3.1 Reactor Types
10.3.2 Design of Microreactors
10.3.3 Scale-up and Operational Maps
10.4 Illustrative Example: Control of Hormone Diseases via Tissue Therapy
10.4.1 Transport Considerations
10.4.2 Selection of Diabetes as Representative Case Study
10.4.3 Encapsulation Motif: Specifications, Design, and Evaluation
10.4.3.1 Physical and Transport Parameters
References
2123ch11.pdf
Table of Contents
Chapter 11: Interstitial Transport in the Brain: Principles for Local Drug Delivery
11.1 Introduction
11.2 Implantable Controlled Delivery Systems for Chemotherapy
11.3 Drug Transport After Release from the Implant
11.4 Application of Diffusion–Elimination Models to Intracranial BCNU Delivery Systems
11.5 Limitations and Extensions of the Diffusion–Elimination Model
11.5.1 Failure of the Model in Certain Situations
11.5.2 Effect of Drug Release Rate
11.5.3 Determinants of Tissue Penetration
11.5.4 Effect of Fluid Convection
11.5.5 Effect of Metabolism
11.6 New Approaches to Drug Delivery Suggested by Modeling
11.7 Conclusion
References
2123ch12.pdf
Table of Contents
SECTION III: Biotechnology
Chapter 12: Tools for Genome Analysis
12.1 General Principles
12.2 Enabling Technologies
12.2.1 Cloning
12.2.2 Electrophoresis
12.2.3 Enzymatic DNA Sequencing
12.2.4 Polymerase Chain Reaction (PCR)
12.2.5 Chemical Synthesis of Oligodeoxynucleotides
12.3 Tools for Genome Analysis
12.3.1 Physical Mapping
12.3.2 DNA Sequencing
12.3.3 Genetic Mapping
12.3.4 Computation
12.4 Conclusions
Acknowledgments
References
2123ch13.pdf
Table of Contents
Chapter 13: Vaccine Production
13.1 Antigen Cultivation
13.1.1 Microbial Cultivation
13.1.1.1 Bacterial Growth
13.1.1.2 Antigen Production
13.1.1.3 Cultivation Technology
13.1.2 Virus Cultivation
13.1.2.1 In Vivo Virus Cultivation
13.1.2.2 Ex Vivo Virus Cultivation
13.2 Downstream Processing
13.2.1 Purification Principles
13.2.1.1 Recovery
13.2.1.2 Isolation
13.2.1.3 Final Purification
13.2.1.4 Inactivation
13.2.2 Purification Examples
13.2.2.1 Bacterial Vaccines
13.2.2.2 Viral Vaccines
13.2.2.3 Antibody Preparations
13.3 Formulation and Delivery
13.3.1 Live Organisms
13.3.2 Subunit Antigens
13.4 Future Trends
13.4.1 Vaccine Cultivation
13.4.2 Downstream Processing
13.4.3 Vaccine Adjuvants and Formulation
13.5 Conclusions
Defining Terms
References
Further Information
2123ch14.pdf
Table of Contents
Chapter 14: Protein Engineering
14.1 Protein Engineering Goals
14.2 Preliminary Requirements
14.3 Rational Mutagenesis
14.3.1 Site-Directed Mutagenesis
14.3.2 Other Methods
14.3.3 An Example: Insulin
14.4 Combinatorial Methods
14.4.1 Library Construction
14.4.2 Screening and Selection Methods
14.4.3 Some Examples
14.5 Assessment of Improvements and Cycle Repetition
14.6 Conclusions
References
Further Information
2123ch15.pdf
Table of Contents
Chapter 15: Metabolic Engineering
15.1 Metabolic Engineering Goals
15.2 Metabolic Networks and Flux Measurements
15.2.1 Network Construction
15.2.2 Flux Measurements
15.3 Modeling of Metabolic Networks
15.3.1 Metabolic Flux Analysis
15.3.2 Metabolic Control Analysis
15.3.3 Kinetic Models
15.3.4 Examples
15.4 Metabolic Pathway Engineering
15.4.1 Recombinant DNA
15.4.2 Viral Gene Delivery
15.4.3 Genetic Interference
15.4.4 Examples
15.5 Summary
References
Further Information
2123ch16.pdf
Table of Contents
Chapter 16: Monoclonal Antibodies and Their Engineered Fragments
16.1 Structure and Function of Antibodies
16.2 Monoclonal Antibody Cloning Techniques
16.2.1 Hybridoma Technology
16.2.2 Repertoire Cloning Technology
16.2.3 Phage Display Technology
16.2.4 Bypassing Immunization
16.3 Monoclonal Antibody Expression Systems
16.3.1 Bacterial Expression
16.3.2 Expression in Lymphoid and Nonlymphoid Systems (Transfectoma Technology)
16.3.3 Expression in Yeast
16.3.4 Expression in Baculovirus
16.3.5 Expression in Plants
16.4 Genetically Engineered Antibodies and Their Fragments
16.5 Applications of Monoclonal Antibodies and Fragments
16.6 Summary
References
2123ch17.pdf
Table of Contents
Chapter 17: Biomolecular Engineering in Oligonucleotide Applications
17.1 Introduction
17.2 Antisense Principle
17.3 Design Parameters
17.3.1 Stability to Extracellular and Intracellular Nucleases
17.3.2 Cellular Delivery and Uptake
17.3.3 Intermolecular Hybridization Affinity
17.4 Other Applications
17.4.1 Aptamers
17.4.2 RNA Interference
17.5 Summary
Abbreviations
References
2123ch18.pdf
Table of Contents
Chapter 18: Gene Therapy
18.1 Background
18.2 Recombinant Retroviruses
18.3 Recombinant Adenoviruses
18.4 Recombinant Adeno-Associated Viruses
18.5 Direct Injection of Naked DNA
18.6 Particle-Mediated Gene Transfer
18.7 Liposome-Mediated Gene Delivery
18.8 Other Gene Transfer Methods
18.9 Summary and Conclusion
Defining Terms
References
2123ch19.pdf
Table of Contents
Chapter 19: Bio-Nanorobotics: State of the Art and Future Challenges
19.1 Introduction
19.2 Nature’s Nanorobotic Devices
19.2.1 Protein-Based Molecular Machines
19.2.1.1 ATP Synthase — A True Nanorotary Motor
19.2.1.2 The Kinesin, Myosin, Dynein, and Flagella Molecular Motors
19.2.2 DNA-Based Molecular Machines
19.2.2.1 The DNA Tweezers
19.2.3 Inorganic (Chemical) Molecular Machines
19.2.3.1 The Rotaxanes
19.2.3.2 The Catenanes
19.2.3.3 Other Inorganic Molecular Machines
19.2.4 Other Protein-Based Motors Under Development
19.2.4.1 Viral Protein Linear Motors
19.2.4.2 Synthetic Contractile Polymers
19.3 Nanorobotics Design and Control
19.3.1 Design of Nanorobotic Systems
19.3.1.1 The Roadmap
19.3.1.2 Design Philosophy and Architecture for the Bio-Nanorobotic Systems
19.3.1.3 Computational and Experimental Tools for Studying Bio-Nanorobotic Systems
19.3.1.4 Nanomanipulation — Virtual Reality-Based Design Techniques
19.3.2 Control of Nanorobotic Systems
19.3.2.1 Internal Control Mechanism — Active and Passive
19.3.2.2 External Control Mechanism
19.4 Conclusions
References
2123ch20.pdf
Table of Contents
SECTION IV: Bionanotechnology
Chapter 20: DNA as a Scaffold for Nano-Structure Assembly
20.1 Introduction
20.2 DNA as a Scaffold for Building Structures
20.3 Coating DNA with Metals or Plastics
20.4 Sodium–Silver Ion Exchange
20.5 Palladium–Amine Covalent Binding
20.6 Patterning Materials on DNA
20.7 Coated DNA Structures in Practice — A PCR Free, Biological Detection, and Identification Systems
20.8 Components
20.9 Sample Preparation
20.10 Future Capabilities
20.11 Conclusion
References
2123ch21.pdf
Table of Contents
Chapter 21: Directed Evolution of Proteins for Device Applications
21.1 Protein-Based Devices
21.2 Bacteriorhodopsin
21.3 Protein Optimization via Mutagenesis
21.4 Directed Evolution
21.5 Conclusions
References
2123ch22.pdf
Table of Contents
Chapter 22: Semiconductor Quantum Dots for Molecular and Cellular Imaging
22.1 Introduction
22.2 Quantum Dots vs. Organic Fluorophores
22.3 Synthesis and Bioconjugation
22.3.1 Synthesis and Capping
22.3.2 Water Solubilization and Bioconjugation
22.4 Biological Applications
22.4.1 Bioanalytic Assays
22.4.2 QD-Encoding
22.4.3 Imaging of Cells and Tissues
22.4.4 In Vivo Animal Imaging
22.5 Future Directions
Acknowledgments
References
2123ch23.pdf
Table of Contents
Chapter 23: Bionanotechnology for Bioanalysis
23.1 Overview
23.2 Nanoparticle Surface Modification
23.3 Nanoparticles for Cellular Imaging
23.4 Nanoparticles for Microarray Technology
23.5 Future Perspectives
Acknowledgments
References
2123ch24.pdf
Table of Contents
Chapter 24: Nano-Hydroxyapatite for Biomedical Applications
24.1 Introduction
24.2 Basic Science of Nano-Hydroxyapatite
24.3 Nano-HA Chemistry
24.4 Nano-HA Mechanics
24.5 Nano-HA Biology In Vitro and In Vivo
24.6 HA Products and Their Applications
24.6.1 Porous Nano-HA Granules or Blocks
24.6.2 Nano-HA Cement
24.6.3 Nano-HA Coating
Acknowledgment
References
2123ch25.pdf
Table of Contents
Chapter 25: Nanotechnology Provides New Tools for Biomedical Optics
25.1 Introduction
25.2 Quantum Dots as Fluorescent Biological Labels
25.3 Gold Nanoparticle Bioconjugate-Based Colorimetric Assays
25.4 Photothermal Therapies
25.5 Silver Plasmon Resonant Particles for Bioassay Applications
References
2123ch26.pdf
Table of Contents
Chapter 26: Nanomaterials Perspectives and Possibilities in Nanomedicine
26.1 Particle-Based Therapeutic Systems
26.1.1 Practical Considerations for Nanoscale Vectors
26.1.2 Example Delivery Nanosystems
26.1.3 Summary
26.2 Tissue Engineering
26.2.1 Surface Molecular Engineering for Controlled Protein Interaction
26.2.1.1 Stealth Materials
26.2.1.2 Biomimetic Materials
26.2.2 Nanostructured Surfaces
26.2.3 Self-Assembled Systems
26.2.4 Summary
26.3 Diagnostic Imaging and Monitoring
26.3.1 Biophotonics
26.3.1.1 Nanoparticles in Imaging
26.3.1.2 Nanosensor Probes
26.3.1.3 Quantum Dots in Imaging
26.3.2 Diagnostic Biosensors
26.3.2.1 Molecular Biointerfaces for Gene and Protein Biorecognition
26.3.2.2 Pathogen Recognition
26.3.3 Summary
26.4 On the Horizons of Nanomedicine
26.5 Conclusions
References
2123ch27.pdf
Table of Contents
Chapter 27: Biomedical Nanoengineering for Nanomedicine
27.1 Nanomaterials and Nanodevices
27.1.1 Fullerenes and Carbon Nanotubes
27.1.2 Dendrimer
27.1.2.1 Nanoparticles and Nanowires
27.2 Biomedical Applications
27.2.1 Prevention
27.2.2 Diagnostics
27.2.3 Treatment
27.3 Conclusion
References
2123ch28.pdf
Table of Contents
Chapter 28: Physiogenomics: Integrating Systems Engineering and Nanotechnology for Personalized Medicine
28.1 Physiogenomics and Nanotechnology
28.1.1 Introduction
28.1.2 Fundamentals of Physiogenomics
28.1.3 Physiotype Models
28.2 Physiogenomic Marker Discovery
28.2.1 Association Screening
28.2.2 Physiogenomic Control and Negative Results
28.3 Physiogenomic Modeling
28.3.1 Model Building
28.3.2 Overall Rationale
28.3.3 Model Parameterization
28.3.4 Model Validation
28.3.5 Multiple Comparison Corrections
28.3.6 Summary of Association Results
28.4 Future Research and Prospects
28.4.1 Future Research
28.4.2 Prospects and Conclusions
References
2123ch29.pdf
Table of Contents
Chapter 29: Bionanotechnology Patenting: Challenges and Opportunities
29.1 Defining Bionanotechnology R&D
29.2 Significance of Patents to Bionanotechnology Commercialization
29.3 The U.S. Patent System and the Criteria for Patenting
29.4 Key Considerations and Strategies for Inventors
29.5 The Bionanotechnology Start-Up and Patents
29.6 Searching Bionanotechnology-Related Patents
29.7 Challenges Facing the U.S. Patent and Trademark Office
References
2123ch30.pdf
Table of Contents
SECTION V: Tissue Engineering
Chapter 30: Fundamentals of Stem Cell Tissue Engineering
30.1 Introduction
30.2 Mesenchymal Stem Cells
30.3 Fundamental Principles
30.3.1 In Vitro Assays for the Osteogenic and Chondrogenic Lineages
30.4 MSCs and Hematopoietic Support
30.4.1 Muscle, Tendon, and Fat
30.4.2 A New Fundamental Role for MSCs
30.4.3 The Use of MSCs Today and Tomorrow
30.5 Cell Targeting
Acknowledgments
References
2123ch31.pdf
Table of Contents
Chapter 31: Growth Factors and Morphogens: Signals for Tissue Engineering
31.1 Introduction
31.2 Tissue Engineering and Morphogenesis
31.3 The Bone Morphogenetic Proteins
31.4 Growth Factors
31.5 BMPs Bind to Extracellular Matrix
31.6 Clinical Applications
31.7 Challenges and Opportunities
Acknowledgments
References
2123ch32.pdf
Table of Contents
Chapter 32: Extracellular Matrix: Structure, Function, and Applications to Tissue Engineering
32.1 Introduction
32.2 ECM and Functional Integration of Implanted Materials
32.3 Basement Membranes and Focal Adhesions
32.4 Focal Adhesions as Signaling Complexes
32.5 ECM and Skeletal Tissues
32.6 Sources of ECM for Tissue Engineering Applications
32.7 Properties of ECM
32.8 Mining the ECM for Functional Motifs
32.8.1 Collagen
32.8.2 Fibronectin
32.8.3 Laminin
32.8.4 Tenascin, Thrombospondin, and Osteonectin/SPARC/BM-40
32.8.5 Proteoglycans and Glycosaminoglycans
32.8.6 Osteopontin
32.9 Summary of Functions of ECM Molecules
32.10 Polymeric Materials and their Surface Modification
32.11 Formation of Gradient Structures
32.12 Delivery of Growth Factors
32.13 Summary and Conclusions
Acknowledgments
References
2123ch33.pdf
Table of Contents
Chapter 33: Mechanical Forces on Cells
33.1 Introduction
33.2 The Role of Cytoskeletal Tension in Anchorage-Dependent Cells
33.3 The Role of ECM Scaffolds in Regulating Cellular Tension
33.3.1 Effects of the Compliance of ECM Scaffolds
33.3.2 Effects of the Spatial Distribution of ECM Ligands
33.3.3 Physicality of ECM Scaffolds in Tissue Engineering
33.4 The Role of Externally Applied Mechanical Forces in Cell Function
33.4.1 Devices and Methodology Used for Mechanical Stimulation of Cells In Vitro
33.4.1.1 Shear Stress
33.4.1.2 Stretch
33.4.1.3 Pressure/Compression
33.4.2 Responses of Cells to Mechanical Stimulation In Vitro
33.4.3 Mechanosensing of Cultured Cells to Externally Applied Mechanical Forces
33.4.3.1 Direct Mechanosensing
33.4.3.2 Indirect Mechanosensing
33.4.4 Applications of Externally Applied Mechanical Forces in Tissue Engineering
33.5 Concluding Remarks
Acknowledgments
References
2123ch34.pdf
Table of Contents
Chapter 34: Cell Adhesion
34.1 Introduction
34.2 Adhesion Receptors in Tissue Structures
34.2.1 Integrins
34.2.2 Cadherins
34.2.3 Immunoglobulins
34.3 Cell Adhesion to Biomaterials
34.3.1 The Role of Interfacial Chemistry in Cell Adhesion
34.3.2 The Role of Interfacial Biochemistry in Cell Adhesion
34.3.3 Biomimetic Approaches to Regulate Cell Adhesion
34.3.4 The Role of Interfacial Topography in Cell Adhesion
34.4 Measurement of Cell Adhesion to Biomaterials
34.4.1 Micropipette Aspiration
34.4.2 Centrifugation
34.4.3 Laminar Flow Chambers
34.4.4 Rotating Disc
34.4.5 Interpretation of Adhesion Data
34.5 Effect of Biomaterial on Physiological Behavior
34.6 Summary
References
2123ch35.pdf
Table of Contents
Chapter 35: Cell Migration
35.1 Introduction
35.2 Characteristics of Mammalian Cell Migration
35.2.1 Cell Movement Cycle
35.2.2 Persistent Random Walk
35.2.3 Cell–Cell Contacts
35.3 Regulation of Cell Movement
35.3.1 Soluble Factors Modulate Cell Movement
35.3.2 ECM Proteins and Cell–Substrate Interactions Regulate Cell Movement
35.3.3 Electrical Fields Direct Cell Movement
35.4 Cell Migration Assays
35.4.1 Cell-Population Assays
35.4.2 Individual-Cell Assays
35.5 Mathematical Models for Cell Migration and Tissue Growth
References
2123ch36.pdf
Table of Contents
Chapter 36: Inflammatory and Immune Responses to Tissue Engineered Devices
36.1 Introduction
36.2 Inflammatory Responses
36.3 Immune Responses
References
2123ch37.pdf
Table of Contents
Chapter 37: Polymeric Scaffolds for Tissue Engineering Applications
37.1 Introduction
37.2 Natural Polymers for Scaffold Fabrication
37.2.1 Polysaccharides
37.2.1.1 Agarose
37.2.1.2 Alginate
37.2.1.3 Hyaluronic Acid
37.2.1.4 Chitosan
37.2.2 Polypeptides
37.2.2.1 Collagen
37.2.2.2 Gelatin
37.2.2.3 Silk
37.3 Synthetic Polymers for Scaffold Fabrication
37.3.1 Polyesters
37.3.1.1 Poly(glycolic) Acid
37.3.1.2 Poly(L-lactic) Acid
37.3.1.3 Poly(D,L-lactic acid-co-glycolic acid)
37.3.1.4 Poly(ε-caprolactone)
37.3.1.5 Poly(propylene fumarate)
37.3.1.6 Polyorthoester
37.3.2 Other Synthetic Polymers
37.3.2.1 Polyanhydride
37.3.2.2 Polyphosphazene
37.3.2.3 Polycarbonate
37.3.2.4 Poly(ethylene glycol)/Poly(ethylene oxide)
37.3.2.5 Polyurethane
37.4 Scaffold Design Properties
37.4.1 Fabrication
37.4.2 Micro-Structure
37.4.3 Macro-Structure
37.4.4 Biocompatibility
37.4.5 Biodegradability
37.4.6 Mechanical Strength
37.5 Summary
References
2123ch38.pdf
Table of Contents
Chapter 38: Calcium Phosphate Ceramics for Bone Tissue Engineering
38.1 Introduction
38.2 Chemico-Physical Properties of Calcium Phosphate Ceramics
38.2.1 Crystallinity
38.2.2 Sintering
38.2.3 Stoichiometry
38.2.3.1 TCP (Ca3(PO4)2)
38.2.3.2 Hydroxyapatite (Ca10(PO4)6(OH)2)
38.2.4 Strength
38.2.5 Porosity
38.2.5.1 Microporosity
38.2.5.2 Macroporosity
38.3 Ca-P Products
38.3.1 Natural Ca-P Ceramics
38.3.2 Injectable Ca-P Cements
38.4 In Vivo Interactions and Osteoinductivity
38.5 Calcium Phosphate Ceramics for Bone Tissue Engineering
38.5.1 Ca-P Ceramics and Osteogenic Cells
38.5.2 Ca-P Ceramics and Osteoinductive Growth Factors
38.5.2.1 Growth Factor Release from Ca-P Ceramics
38.5.2.2 Growth Factor Loading in Ca-P Ceramics
38.5.2.3 Osteoinductive Capacity of Growth Factor Loaded Ca-P Ceramics
38.6 Conclusion and Future Perspective
References
2123ch39.pdf
Table of Contents
Chapter 39: Biomimetic Materials
39.1 Extracellular Matrices: Nature’s Engineered Scaffolds
39.2 Bioadhesive Materials
39.3 Materials Engineered to Interact with Growth Factors
39.4 Protease-Degradable Materials
39.5 Artificial Proteins as Building Elements for Matrices
39.6 Conclusions and Outlook
References
2123ch40.pdf
Table of Contents
Chapter 40: Nanocomposite Scaffolds for Tissue Engineering
40.1 Introduction
40.2 Nanocomposite Materials
40.2.1 Nanomaterials Overview
40.2.2 Functionalized Alumoxane Nanocomposites
40.2.3 Polymer-Layered Silicate Nanocomposites
40.2.4 Hydroxyapatite Nanocomposites
40.2.5 Other Ceramic Nanocomposites
40.2.6 Carbon Nanotube Nanocomposites
40.3 Conclusions
Acknowledgments
References
2123ch41.pdf
Table of Contents
Chapter 41: Roles of Thermodynamic State and Molecular Mobility in Biopreservation
41.1 Water–Solute Interactions and Intracellular Transport
41.1.1 Intracellular Water and Molecular Mobility
41.1.2 Transmembrane Water Transport Effects
41.2 Molecular Mobility in Preservation
41.2.1 Molecular Mobility in Supercooling and Phase Change
41.2.2 Cryopreservation
41.2.3 Vitrification
41.2.4 Vitrification by Ultrafast Cooling
41.2.5 Vitrification by Desiccation
41.2.6 Lyophilization
41.3 Storage
41.4 Summary
Acknowledgments
References
2123ch42.pdf
Table of Contents
Chapter 42: Drug Delivery
42.1 Introduction
42.1.1 Significance
42.1.2 Goals of Drug Delivery
42.2 Mechanisms of Drug Delivery
42.2.1 Diffusion
42.2.2 Erosion
42.2.3 Swelling
42.2.4 Competing Mechanisms and Overall Kinetics
42.3 Protein Drug Properties
42.4 Drug Delivery in Tissue Engineering
42.4.1 The Use of Classical Drug-Delivery Systems
42.4.1.1 Monolithic Systems
42.4.2 The Delivery of Drugs via Cell Carriers
42.4.2.1 Cell Carriers Loaded with Drug-Delivery systems
42.4.2.2 Cell Carriers Loaded with Drugs
42.5 Outlook
References
2123ch43.pdf
Table of Contents
Chapter 43: Gene Therapy
43.1 Introduction
43.2 Nucleotides for Delivery
43.2.1 DNA (deoxyribonucleic acid)
43.2.1.1 Plasmids
43.2.1.2 Nucleotide Decoys
43.2.2 RNA
43.3 Gene Delivery
43.3.1 Biological Delivery Methods
43.3.2 Chemical Delivery Methods
43.3.3 Physical Delivery Methods
43.4 Intracellular Pathways
43.5 Cell and Tissue Targeting
43.6 Applications
43.6.1 In Vitro
43.6.2 Ex Vivo
43.6.3 In Vivo
43.7 Clinical Applications
43.8 Summary
References
2123ch44.pdf
Table of Contents
Chapter 44: Tissue Engineering Bioreactors
44.1 Introduction
44.2 Most Common Bioreactors in Tissue Engineering
44.2.1 Spinner Flask
44.2.2 Rotating-Wall Vessels
44.2.3 Perfusion Chambers and Flow Perfusion Systems
44.3 Cell Seeding in Bioreactors
44.4 Bioreactor Applications in Functional Tissues
44.4.1 Tissues of the Cardiovascular System
44.4.1.1 Vascular Grafts
44.4.1.2 Heart Valves
44.4.2 Bone
44.4.3 Cartilage
44.4.4 Anterior Cruciate Ligament and Tendons
44.4.5 Other Tissues
44.5 Design Considerations
44.6 Challenges in Bioreactor Technologies
Acknowledgment
References
2123ch45.pdf
Table of Contents
Chapter 45: Animal Models for Evaluation of Tissue-Engineered Orthopedic Implants
45.1 Introduction
45.2 Animal Model Selection
45.3 Commonly Used Animals
45.4 Specific Animal Models
45.4.1 Biocompatibility
45.4.2 Biodegradation
45.4.3 Osteogenesis
45.4.4 Chondrogenesis
45.5 Experimental Studies
45.5.1 Experimental Design
45.5.2 Evaluation Methods
References
2123ch46.pdf
Table of Contents
Chapter 46: The Regulation of Engineered Tissues: Emerging Approaches
46.1 Introduction
46.2 FDA Regulation
46.2.1 Classification of Medical Products
46.2.2 Special Product Designations
46.2.3 Human Cellular and Tissue-Based Products
46.2.4 Marketing Review and Approval Pathways
46.2.4.1 Devices
46.2.4.2 Biologics
46.3 Regulation of Pharmaceutical/Medical Human Tissue Products in Europe
46.4 Regulation of Pharmaceutical/Medical Human Tissue Products in Japan
46.5 Other Considerations Relevant to Engineered Tissues
46.5.1 FDA Regulation and Product Liability
46.5.2 Ownership of Human Tissues
46.6 Conclusion
References
2123ch47.pdf
Table of Contents
Chapter 47: Bioengineering of Human Skin Substitutes
47.1 Introduction
47.2 Objectives of Skin Substitutes
47.3 Composition of Skin Substitutes
47.3.1 Acellular Skin Substitutes
47.3.2 Allogeneic Cellular Skin Substitutes
47.3.3 Autologous Cellular Skin Substitutes
47.4 Clinical Considerations
47.5 Assessment
47.6 Regulatory Issues
47.7 Future Directions
47.7.1 Pigmentation
47.7.2 In Vitro Angiogenesis
47.7.3 Cutaneous Gene Therapy
47.8 Conclusions
References
2123ch48.pdf
Table of Contents
Chapter 48: Nerve Regeneration: Tissue Engineering Strategies
48.1 Introduction
48.2 Neural Regeneration
48.2.1 Peripheral Nervous System
48.2.2 Central Nervous System
48.3 Guidance Strategies for Regeneration
48.3.1 Autografts
48.3.2 Allografts and Acellular Nerve Matrices
48.3.3 Entubulization Using Nerve Conduits
48.4 Enhancing Neural Regeneration Using Entubulization Strategies
48.4.1 Physical Modifications
48.4.1.1 Microtexturing
48.4.1.2 Micropatterning
48.4.2 Biochemical Modifications: Creating an “Active” Nerve Conduit
48.4.2.1 Chemical Patterning
48.4.2.2 Matrices Within Polymer Conduits
48.4.2.3 Neurotrophins
48.4.3 Cellular Modifications
48.4.3.1 Cell Encapsulation
48.4.3.2 Cell Implantation
48.5 Conclusions
Acknowledgments
References
