Download Biomedical Engineering Hndbk [Vol 3 of 3 - Tissue Engineering, Artificial Organs] 3rd ed - J. Bronzino (CRC, 2006) WW PDF

TitleBiomedical Engineering Hndbk [Vol 3 of 3 - Tissue Engineering, Artificial Organs] 3rd ed - J. Bronzino (CRC, 2006) WW
File Size51.8 MB
Total Pages779
Table of Contents
	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
	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
	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
	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
	Table of Contents
	SECTION II: Transport Phenomena and Biomimetic Systems
	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
	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
	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 Formulations 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
	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 Constitutive Equations Conservation (Field) Equations Turbulence and Instabilities
			7.2.2 Flow in Tubes Steady Poiseuille Flow Entrance Flow 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
	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
	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
	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 Blood Bone Marrow Microenvironment
			10.2.3 Communication Cellular Communication Within Tissues Soluble Growth Factors Direct Cell-to-Cell Contact Extracellular Matrix and Cell–Tissue Interactions 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 Physical and Transport Parameters
	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
	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
	Table of Contents
	Chapter 13: Vaccine Production
		13.1 Antigen Cultivation
			13.1.1 Microbial Cultivation Bacterial Growth Antigen Production Cultivation Technology
			13.1.2 Virus Cultivation In Vivo Virus Cultivation Ex Vivo Virus Cultivation
		13.2 Downstream Processing
			13.2.1 Purification Principles Recovery Isolation Final Purification Inactivation
			13.2.2 Purification Examples Bacterial Vaccines Viral Vaccines 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
		Further Information
	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
		Further Information
	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
		Further Information
	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
	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
	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
	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 ATP Synthase — A True Nanorotary Motor The Kinesin, Myosin, Dynein, and Flagella Molecular Motors
			19.2.2 DNA-Based Molecular Machines The DNA Tweezers
			19.2.3 Inorganic (Chemical) Molecular Machines The Rotaxanes The Catenanes Other Inorganic Molecular Machines
			19.2.4 Other Protein-Based Motors Under Development Viral Protein Linear Motors Synthetic Contractile Polymers
		19.3 Nanorobotics Design and Control
			19.3.1 Design of Nanorobotic Systems The Roadmap Design Philosophy and Architecture for the Bio-Nanorobotic Systems Computational and Experimental Tools for Studying Bio-Nanorobotic Systems Nanomanipulation — Virtual Reality-Based Design Techniques
			19.3.2 Control of Nanorobotic Systems Internal Control Mechanism — Active and Passive External Control Mechanism
		19.4 Conclusions
	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
	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
	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
	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
	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
	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
	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 Stealth Materials 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 Nanoparticles in Imaging Nanosensor Probes Quantum Dots in Imaging
			26.3.2 Diagnostic Biosensors Molecular Biointerfaces for Gene and Protein Biorecognition Pathogen Recognition
			26.3.3 Summary
		26.4 On the Horizons of Nanomedicine
		26.5 Conclusions
	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 Nanoparticles and Nanowires
		27.2 Biomedical Applications
			27.2.1 Prevention
			27.2.2 Diagnostics
			27.2.3 Treatment
		27.3 Conclusion
	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
	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
	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
	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
	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
	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 Shear Stress Stretch 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 Direct Mechanosensing Indirect Mechanosensing
			33.4.4 Applications of Externally Applied Mechanical Forces in Tissue Engineering
		33.5 Concluding Remarks
	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
	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
	Table of Contents
	Chapter 36: Inflammatory and Immune Responses to Tissue Engineered Devices
		36.1 Introduction
		36.2 Inflammatory Responses
		36.3 Immune Responses
	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 Agarose Alginate Hyaluronic Acid Chitosan
			37.2.2 Polypeptides Collagen Gelatin Silk
		37.3 Synthetic Polymers for Scaffold Fabrication
			37.3.1 Polyesters Poly(glycolic) Acid Poly(L-lactic) Acid Poly(D,L-lactic acid-co-glycolic acid) Poly(ε-caprolactone) Poly(propylene fumarate) Polyorthoester
			37.3.2 Other Synthetic Polymers Polyanhydride Polyphosphazene Polycarbonate Poly(ethylene glycol)/Poly(ethylene oxide) 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
	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 TCP (Ca3(PO4)2) Hydroxyapatite (Ca10(PO4)6(OH)2)
			38.2.4 Strength
			38.2.5 Porosity Microporosity 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 Growth Factor Release from Ca-P Ceramics Growth Factor Loading in Ca-P Ceramics Osteoinductive Capacity of Growth Factor Loaded Ca-P Ceramics
		38.6 Conclusion and Future Perspective
	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
	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
	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
	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 Monolithic Systems
			42.4.2 The Delivery of Drugs via Cell Carriers Cell Carriers Loaded with Drug-Delivery systems Cell Carriers Loaded with Drugs
		42.5 Outlook
	Table of Contents
	Chapter 43: Gene Therapy
		43.1 Introduction
		43.2 Nucleotides for Delivery
			43.2.1 DNA (deoxyribonucleic acid) Plasmids 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
	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 Vascular Grafts 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
	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
	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 Devices 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
	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
	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 Microtexturing Micropatterning
			48.4.2 Biochemical Modifications: Creating an “Active” Nerve Conduit Chemical Patterning Matrices Within Polymer Conduits Neurotrophins
			48.4.3 Cellular Modifications Cell Encapsulation Cell Implantation
		48.5 Conclusions
Document Text Contents
Page 1

© 2006 by Taylor & Francis Group, LLC

The Biomedical Engineering Handbook
Third Edition

Tissue Engineering
and Artificial Organs

Page 2

© 2006 by Taylor & Francis Group, LLC

The Electrical Engineering Handbook Series

Series Editor

Richard C. Dorf
University of California, Davis

Titles Included in the Series

The Handbook of Ad Hoc Wireless Networks, Mohammad Ilyas
The Avionics Handbook, Cary R. Spitzer
The Biomedical Engineering Handbook, Third Edition, Joseph D. Bronzino
The Circuits and Filters Handbook, Second Edition, Wai-Kai Chen
The Communications Handbook, Second Edition, Jerry Gibson
The Computer Engineering Handbook, Vojin G. Oklobdzija
The Control Handbook, William S. Levine
The CRC Handbook of Engineering Tables, Richard C. Dorf
The Digital Signal Processing Handbook, Vijay K. Madisetti and Douglas Williams
The Electrical Engineering Handbook, Third Edition, Richard C. Dorf
The Electric Power Engineering Handbook, Leo L. Grigsby
The Electronics Handbook, Second Edition, Jerry C. Whitaker
The Engineering Handbook, Third Edition, Richard C. Dorf
The Handbook of Formulas and Tables for Signal Processing, Alexander D. Poularikas
The Handbook of Nanoscience, Engineering, and Technology, William A. Goddard, III,

Donald W. Brenner, Sergey E. Lyshevski, and Gerald J. Iafrate
The Handbook of Optical Communication Networks, Mohammad Ilyas and

Hussein T. Mouftah
The Industrial Electronics Handbook, J. David Irwin
The Measurement, Instrumentation, and Sensors Handbook, John G. Webster
The Mechanical Systems Design Handbook, Osita D.I. Nwokah and Yidirim Hurmuzlu
The Mechatronics Handbook, Robert H. Bishop
The Mobile Communications Handbook, Second Edition, Jerry D. Gibson
The Ocean Engineering Handbook, Ferial El-Hawary
The RF and Microwave Handbook, Mike Golio
The Technology Management Handbook, Richard C. Dorf
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The VLSI Handbook, Wai-Kai Chen

Page 389

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22-4 Tissue Engineering and Artificial Organs



Ligand exchange

Quantum dot water solubilization

Hydrophobic interactions

aqueous solution. Ligands are drawn disproportionately large for detail. (a) TOPO ligands may be exchanged for
hetero-bifunctional ligands for dispersion in aqueous solution. This scheme can be used to generate a hydrophilic
QD with carboxylic acids or a shell of silica on the QD surface. (b) The hydrophobic ligands may be retained
on the QD surface and rendered water soluble through micelle-like interactions with an amphiphilic polymer like
octylamine-modified polyacrylic acid.

22.4 Biological Applications

Fluorescence is a sensitive and routine means for monitoring biological events using fluorescent dyes and
fluorescent proteins. Since 1998, QDs have also been used as biological labels in a variety of bioassays,
some of which would not have been possible with conventional fluorophores. In vitro bioanalytic assays
were developed by using QD-tagged antibodies, FRET-QD biosensors, as well as by using QD-encoded
microbeads. In addition to solution-based assays, the spectroscopic advantages of QDs have also allowed

(See color insert.) Diagram of two general strategies for phase transfer of TOPO-coated QDs into

Page 390

© 2006 by Taylor & Francis Group, LLC

Semiconductor Quantum Dots for Molecular and Cellular Imaging 22-5

sensitive optical imaging in living cells and animal models. Many reports have concentrated on simply
replacing organic dyes with QDs, without utilizing their unique properties. This analysis will focus on
the publications that have exploited their resistance to photobleaching and potential for multiplexed

22.4.1 Bioanalytic Assays

Organic fluorophores are commonly used as reporters in a large number of in vitro bioassays, such as
quantitative immunoassays and fluorescence quenching assays for macromolecular interactions. High
sensitivity has been realized with the use of organic dyes, but the spectral properties of QDs could lead
to further improvements. Research in the application of QDs for in vitro bioanalysis has been advanced
primarily by Mattoussi and his coworkers at the U.S. Naval Research Laboratory [9,10], and can be divided
into two areas: immunoassays and biosensors.

Immunoassays typically involve the specific binding of a labeled antibody to an analyte, followed by
physical removal of unbound antibody to allow the quantification of the bound label. QDs have been
conjugated to antibodies for use in an assortment of these fluoroimmunoassays for detection of proteins
and small molecules [10]. The results of these studies proved that QDs may be used as “generalized”
reporters in immunoassays, but did not demonstrate an advantage over organic fluorophores, in that
their sensitivity was comparable to that of commercial assays (protein concentrations down to 2 ng/ml,
or 100 pM) [11]. The main advantages of QDs for immunoassays are their narrow, symmetric emission
profiles and the excitability of many different QDs with a single light source, allowing the detection of
multiple analytes simultaneously. Taking advantage of these spectral properties, Goldman et al. [10] sim-
ultaneously detected four toxins using four different QDs, emitting between 510 and 610, in a sandwich
immunoassay configuration. Although there was spectral overlap of the emission peaks, deconvolution
of the spectra revealed fluorescence contributions from all four toxins. This assay was far from quantit-
ative, however, and it is apparent that fine-tuning of antibody cross-reactivity will be required to make
multiplexed immunoassays useful.

Whereas immunoassays require the physical separation of unbound QD conjugates prior to analysis,
biosensors can be developed to detect biomolecular targets on a real-time or continuous basis. QDs
are ideal for biosensor applications due to their resistance to photobleaching, allowing for continuous
monitoring of a signal. Fluorescence resonance energy transfer (FRET) has been the major proposed
mechanism to render QDs switchable from a quenched “off” state to a fluorescent “on” state. FRET is
the nonradiative energy transfer from an excited donor fluorophore to an acceptor. The acceptor can be
any molecule (another nanoparticle, a nonemissive organic dye, or fluorophore) that absorbs radiation
at the wavelength of donor emission. QDs are promising donors for FRET-based applications due to
their continuously tunable emissions that can be matched to any desired acceptor, and their broadband
absorption, allowing excitation at a short wavelength that does not directly excite the acceptor.

It has been confirmed that QDs can be FRET donors, quenchable with efficiencies up to 99%, using
organic fluorophores, nonemissive dyes, gold nanoparticles, or other QDs as acceptors. Medintz et al. [9]
used QDs conjugated to maltose binding proteins as an in situ biosensor for carbohydrate detection.
Adding a maltose derivative covalently bound to a FRET acceptor dye caused QD quenching, and fluor-
escence was restored upon addition of native maltose, which displaced the sugar-dye compound. A key
element of this work was that the physical orientation and stoichiometry of the maltose receptors on
the QDs were controlled so that the restoration of QD fluorescence upon maltose addition could be
directly related to maltose concentration. Although the FRET quenching efficiency was low, this work
demonstrates the potential of QD-based in situ biosensing.

22.4.2 QD-Encoding

Rather than using single QDs for biological detection schemes, it has been proposed that different colors
of QDs can be combined into a larger structure, such as a microbead, to yield an “optical barcode” [5].

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Nerve Regeneration 48-21

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