Biomaterials Science: An introduction to materials in medicine

Front Cover
Biomaterials Science: An Introduction to Materials in Medicine
Copyright
Contents
Contributors
Preface
How to Use this Book
Introduction
	Biomaterials Science: An Evolving, Multidisciplinary Endeavor
		BIOMATERIALS AND BIOMATERIALS SCIENCE
		KEY DEFINITIONS
		THE EVOLUTION OF THE BIOMATERIALS FIELD
		EXAMPLES OF TODAY’S BIOMATERIALS APPLICATIONS
		CHARACTERISTICS OF BIOMATERIALS SCIENCE
		SUBJECTS INTEGRAL TO BIOMATERIALS SCIENCE
		BIOMATERIALS LITERATURE
		BIOMATERIALS SOCIETIES
		SUMMARY
		BIBLIOGRAPHY
A HISTORY OF BIOMATERIALS
	BIOMATERIALS BEFORE WORLD WAR II
	WORLD WAR II TO THE MODERN ERA: THE SURGEON/PHYSICIAN HERO
	DESIGNED BIOMATERIALS
	THE CONTEMPORARY ERA (MODERN BIOLOGY AND MODERN MATERIALS)
	CONCLUSIONS
	BIBLIOGRAPHY
PART I - Materials Science
and Engineering
	SECTION I.1 - Properties of Materials
		CHAPTER I.1.1 INTRODUCTION: PROPERTIES OF MATERIALS: THE PALETTE OF THE BIOMATERIALS ENGINEER
		CHAPTER I.1.2 THE NATURE OF MATTER AND MATERIALS
			INTRODUCTION
			ATOMS AND MOLECULES
			MOLECULAR ASSEMBLIES
			SURFACES
			CONCLUSION
		CHAPTER I.1.3 BULK PROPERTIES OF MATERIALS
			INTRODUCTION
			BIBLIOGRAPHY
			LOAD, NOMINAL STRESS, EXTENSION, AND NOMINAL STRAIN
			TRUE STRESS AND TRUE STRAIN
			SHEAR STRESS AND SHEAR STRAIN
			BULK MECHANICAL PROPERTIES DETERMINED FROM STRESS–STRAIN PLOTS
			OTHER BULK PROPERTIES
			WORKED EXAMPLE
		CHAPTER I.1.4 FINITE ELEMENTANALYSIS IN BIOMECHANICS
			INTRODUCTION
			BIBLIOGRAPHY
			OVERVIEW OF THE FINITE ELEMENTMETHOD
			BIOMECHANICS EXAMPLES
			CONCLUSION
		CHAPTER I.1.5 SURFACE PROPERTIES AND SURFACE CHARACTERIZATION OF BIOMATERIALS
			INTRODUCTION
			SURFACE ANALYSIS TECHNIQUES: PRINCIPLES AND METHODS
			STUDIES WITH SURFACE METHODS
			CONCLUSIONS
			ACKNOWLEDGMENT
			BIBLIOGRAPHY
		CHAPTER I.1.6 ROLE OF WATERIN BIOMATERIALS
			WATER: THE SPECIAL MOLECULE
			WATER: STRUCTURE
			WATER: SIGNIFICANCE FOR BIOMATERIALS
			BIBLIOGRAPHY
	SECTION I.2 - Classes of Materials Used in Medicine
		Chapter I.2.2 Polymers: Basic Principles
		INTRODUCTION
		THE POLYMER MOLECULE
		MOLECULAR WEIGHT
		CONNECTING PHYSICAL BEHAVIOR WITH CHEMICAL CHARACTERISTICS
		POLYMER SYNTHESIS
		CASE STUDIES
		THE PRESENT AND THE FUTURE
		BIBLIOGRAPHY
		A. Polyurethanes
		INTRODUCTION
		ANATOMY OF A POLYURETHANE MOLECULE
		THE PHYSICAL PROPERTIES OF POLYURETHANES
		POLYURETHANE SYNTHESIS
		B. Silicones
		CONCLUDING REMARKS
		BIBLIOGRAPHY
		CHEMICAL STRUCTURE AND NOMENCLATURE
		CONCLUSION
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		C. FLUORINATED BIOMATERIALS
		INTRODUCTION
		INTERESTING FLUOROPOLYMER CHEMICAL AND PHYSICAL PROPERTIES DERIVED FROM THEIR POLYMER CHEMISTRY, MOLECULAR STRUCTURE, AND BONDING
		DISTINGUISHING THE DIFFERENT FLUOROPOLYMERS
		BIOMEDICAL APPLICATIONS
		SUMMARY
		GLOSSARY
		BIBLIOGRAPHY
		D. Acrylics
		INTRODUCTION
		MONO- AND MULTI-METHACRYLATE MONOMERS
		SUMMARY
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER I.2.3 METALS: BASIC
PRINCIPLES
		INTRODUCTION
		STEPS IN THE FABRICATION OF METALLIC BIOMATERIALS
		MICROSTRUCTURES AND PROPERTIES OF IMPLANT METALS
		CONCLUDING REMARKS
		BIBLIOGRAPHY
		A. Titanium and Nitinol (NiTi)
		FABRICATION
		CORROSION RESISTANCE
		BIOCOMPATIBILITY AND SURFACE MODIFICATION
		MECHANICAL PROPERTIES
		NITI ALLOY
		SURFACE MODIFICATIONS OF NITI
		APPLICATIONS
		BIBLIOGRAPHY
		B. Stainless Steels
		INTRODUCTION
		METALLURGICAL AND CHEMICAL CONSIDERATIONS
		MECHANICAL PROPERTIES
		CORROSION BEHAVIOR
		SUMMARY
		BIBLIOGRAPHY
		TYPES OF BIOCERAMICS: TISSUE ATTACHMENT
		CHARACTERISTICS AND PROCESSING OF BIOCERAMICS
		NEARLY INERT CRYSTALLINE CERAMICS
		POROUS CERAMICS
		BIOACTIVE GLASSES AND GLASS-CERAMICS
		BIOACTIVITY REACTION STAGES
		CALCIUM PHOSPHATE CERAMICS
		CALCIUM PHOSPHATE COATINGS
		CALCIUM PHOSPHATE IMPLANTS: MECHANICAL PROPERTIES AND POROSITY
		RESORBABLE CALCIUM PHOSPHATES
		CALCIUM PHOSPHATE BONE CEMENTS
		CLINICAL APPLICATIONS OF HA
		REFERENCES
		A. NATURAL AND SYNTHETIC
HYDROXYAPATITES
		INTRODUCTION
		APPLICATIONS OF HAP CERAMICS
		SYNTHESIS OF HAP CERAMICS
		STRUCTURE CHARACTERIZATION OF HAP CERAMICS
		STABILITY, BIOCOMPATIBILITY, AND OSTEOINTEGRATION OF HAP CERAMICS
		REFERENCES
		B. Alumina
		INTRODUCTION
		PRODUCTION OF ALUMINA
		STRUCTURE OF ALUMINA
		PROPERTIES OF ALUMINA
		ALUMINA AS A BIOMATERIAL
		ALUMINA IN JOINT REPLACEMENTS
		ALUMINA IN BONE SPACERS
		ALUMINA IN DENTAL APPLICATIONS
		OTHER APPLICATIONS OF ALUMINA
		ALUMINA MATRIX COMPOSITES
		CONCLUSION
		BIBLIOGRAPHY
		CHAPTER I.2.5 HYDROGELS
		INTRODUCTION
		CLASSIFICATION AND BASIC STRUCTURES OF HYDROGELS
		SYNTHESIS OF HYDROGELS
		SWELLING BEHAVIOR OF HYDROGELS
		DETERMINATION OF STRUCTURAL CHARACTERISTICS
		BIOMEDICAL HYDROGELS
		“SMART” OR “INTELLIGENT,” STIMULI-RESPONSIVE HYDROGELS AND THEIR APPLICATIONS
		BIOMEDICAL APPLICATIONS OF HYDROGELS
		BIBLIOGRAPHY
		CHAPTER I.2.6 DEGRADABLE
AND RESORBABLE BIOMATERIALS
		INTRODUCTION
		DEFINITIONS RELATING TO THE PROCESSES OF DEGRADATION VERSUS BIODEGRADATION, AND EROSION VERSUS BIOEROSION
		OVERVIEW OF CURRENTLY AVAILABLE DEGRADABLE POLYMERS
		APPLICATIONS OF SYNTHETIC, DEGRADABLE POLYMERS AS BIOMATERIALS
		GLOSSARY OF KEY TERMS
		BIBLIOGRAPHY
		CHAPTER I.2.7 ENGINEERED NATURAL MATERIALS
		INTRODUCTION TO COMMONLY USED NATURAL MATERIALS
		HA IN MEDICINE: THE OLD AND THE NEW
		RECREATING THE EXTRACELLULAR MATRIX
		MEETING THE TRANSLATIONAL CHALLENGE
		GLOSSARY OF ACRONYMS
		DISCLOSURE STATEMENT
		BIBLIOGRAPHY
		CHAPTER I.2.8 PYROLYTIC CARBON FOR LONG-TERM MEDICAL IMPLANTS
		INTRODUCTION
		ELEMENTAL CARBON
		PYROLYTIC CARBON (PYC)
		STEPS IN THE FABRICATION OF PYROLYTIC CARBON COMPONENTS
		BIOCOMPATIBILITY OF PYROLYTIC CARBON
		CLINICAL APPLICATIONS
		CONCLUSION
		BIBLIOGRAPHY
		CHAPTER I.2.9 COMPOSITES
		INTRODUCTION
		REINFORCING SYSTEMS
		MATRIX SYSTEMS
		FABRICATION OF COMPOSITES
		ABSORBABLE MATRIX COMPOSITES
		NON-ABSORBABLE MATRIX COMPOSITES
		SUMMARY
		APPENDIX 1: MECHANICAL AND PHYSICAL PROPERTIES OF COMPOSITES
		CONTINUOUS FIBER COMPOSITES
		SHORT-FIBER COMPOSITES
		PARTICULATE COMPOSITES
		GLOSSARY OF TERMS
		BIBLIOGRAPHY
		CHAPTER I.2.10 NON-FOULING
SURFACES
		INTRODUCTION
		BACKGROUND
		CONCLUSIONS AND PERSPECTIVES
		BIBLIOGRAPHY
		INTRODUCTION
		SMART POLYMERS IN SOLUTION
		SMART POLYMER–PROTEIN BIOCONJUGATES IN SOLUTION
		SMART POLYMERS AND THEIR BIOMOLECULE CONJUGATES ON SURFACES
		SITE-SPECIFIC SMART POLYMER BIOCONJUGATES
		SMART POLYMER HYDROGELS
		CONCLUSIONS
		BIBLIOGRAPHY
		INTRODUCTION
		GENERAL PRINCIPLES
		METHODS FOR MODIFYING THE SURFACES OF MATERIALS
		LAYER-BY-LAYER DEPOSITION AND MULTILAYER POLYELECTROLYTE DEPOSITION
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER I.2.13 SURFACE PATTERNING
		INTRODUCTION
		COMMON CONCERNS IN BIOMOLECULAR SURFACE PATTERNING
		PATTERNING TECHNIQUES
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER I.2.14 MEDICAL FIBERS AND BIOTEXTILES
		FIBER FORMING POLYMERS
		MEDICAL FIBERS
		TEXTILE STRUCTURES
		FINISHING
		BIOTEXTILE PRODUCTS
		FUTURE DIRECTIONS
		ACKNOWLEDGMENTS
		REFERENCES
		CHAPTER I.2.15 TEXTURED
AND POROUS MATERIALS
		INTRODUCTION
		STIMULATING TISSUE INGROWTH
		DISRUPTING FIBROSIS
		PROMOTING ANGIOGENESIS
		CONCLUSION
		BIBLIOGRAPHY
		CHAPTER I.2.16 ELECTROSPINNING
FUNDAMENTALS
AND APPLICATIONS
		MOTIVATION FOR USING ELECTROSPUN MEMBRANES
		HISTORICAL PERSPECTIVE
		CHARACTERIZATION METHODS
		BIOMEDICAL APPLICATIONS FOR ELECTROSPUN MATERIALS
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER I.2.17 SURFACE-IMMOBILIZED
BIOMOLECULES
		INTRODUCTION
		PATTERNED SURFACE COMPOSITIONS
		IMMOBILIZED BIOMOLECULES AND THEIR USES
		IMMOBILIZED CELL LIGANDS AND CELLS
		IMMOBILIZATION METHODS
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER I.2.18 BIOMIMETIC
MATERIALS
		INTRODUCTION: WHAT ARE BIOMIMETIC MATERIALS?
		A CLASSIFICATION OF BIOMIMETIC MATERIALS
		THE ORIGINS OF BIOMIMICRY
		SOME ATTRACTIONS OF BIOMIMICRY
		LIMITATIONS OF BIOMIMICRY
		THE FUTURE OF BIOMIMICRY IN BIOMATERIALS SCIENCE
		ACKNOWLEDGMENT
		WORKED EXAMPLE
		BIBLIOGRAPHY
		CHAPTER I.2.19 MICROPARTICLES
AND NANOPARTICLES
		INTRODUCTION
		MICROPARTICLES
		MICROPARTICLE PREPARATION
		SUBMICRON-SIZED PARTICLES
		NANOPARTICLES
		MATERIALS USED FOR NANOPARTICLE SYNTHESIS
		NANOPARTICLE PREPARATION
		SURFACE MODIFICATION OF MICRO/NANOPARTICLES
		CHARACTERIZATION OF MICRO/NANOPARTICLES
		APPLICATIONS OF MICRO/NANOPARTICLES
		CHALLENGES FACING NANOPARTICLES
		CONCLUDING REMARKS
		BIBLIOGRAPHY
PART II - Biology and Medicine
	SECTION II.1 - Some Background Concepts
		CHAPTER II.1.1 INTRODUCTION:BIOLOGYAND MEDICINE – KEYCONCEPTS IN THE USE OFBIOMATERIALS IN SURGERYAND MEDICAL DEVICES
		CHAPTER II.1.2 ADSORBED PROTEINS ON BIOMATERIALS
		INTRODUCTION
		EXAMPLES OF THE EFFECTS OF ADHESION PROTEINS ON CELLULAR INTERACTIONS WITH MATERIALS
		THE ADSORPTION BEHAVIOR OF PROTEINS AT SOLID–LIQUID INTERFACES
		MOLECULAR SPREADING EVENTS: CONFORMATIONAL AND BIOLOGICAL CHANGES IN ADSORBED PROTEINS
		THE IMPORTANCE OF ADSORBED PROTEINS IN BIOMATERIALS
		BIBLIOGRAPHY
		CHAPTER II.1.3 CELLS AND SURFACES
IN VITRO
		INTRODUCTION
		A BASIC OVERVIEW OF CELL CULTURE
		UNDERSTANDING CELL–SUBSTRATE INTERACTIONS
		CELL RESPONSE TO SUBSTRATE CHEMISTRY
		CELL RESPONSE TO SUBSTRATE TOPOGRAPHY
		CELL RESPONSE TO SUBSTRATE ELASTICITY
		CELL RESPONSE TO MECHANICAL DEFORMATION (STRAIN)
		COMPARISON AND EVALUATION OF SUBSTRATE CUES
		SUMMARY
		GLOSSARY OF TERMS
		BIBLIOGRAPHY
		Chapter II.1.4 Cell Function and Response to Injury
		NORMAL CELL HOUSEKEEPING
		THE PLASMA MEMBRANE: PROTECTION, NUTRIENT ACQUISITION, AND COMMUNICATION
		THE CYTOSKELETON: CELLULAR INTEGRITY AND MOVEMENT
		THE NUCLEUS: CENTRAL CONTROL
		ROUGH AND SMOOTH ENDOPLASMIC RETICULUM, AND GOLGI APPARATUS: BIOSYNTHETIC MACHINERY
		LYSOSOMES, PROTEASOMES AND PEROXISOMES: WASTE DISPOSAL
		MITOCHONDRIA: ENERGY GENERATION
		CELL SPECIALIZATION AND DIFFERENTIATION
		CELL REGENERATION AND PROLIFERATION
		CELL INJURY AND REGENERATION
		CAUSES OF CELL INJURY
		PATHOGENESIS OF CELL INJURY
		RESPONSES TO CELL INJURY
		REVERSIBLE VERSUS IRREVERSIBLE INJURY
		NECROSIS
		APOPTOSIS
		BIBLIOGRAPHY
		CHAPTER II.1.5 TISSUES, THEEXTRACELLULAR MATRIX, ANDCELL–BIOMATERIAL INTERACTIONS
		STRUCTURE AND FUNCTION OF NORMAL TISSUES
		BASIC TISSUES
		TISSUE RESPONSE TO INJURY: INFLAMMATION, REPAIR, AND REGENERATION
		TECHNIQUES FOR ANALYSIS OF CELLS AND TISSUES
		REGENERATIVE CAPACITY OF CELLS AND TISSUES
		CELL/TISSUE–BIOMATERIALS INTERACTIONS
		BIBLIOGRAPHY
		CELLULAR DETECTION OF MECHANICAL FORCES
		BLOOD VESSELS
		INTERSTITIAL FLUID
		BONE AND CARTILAGE
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER II.1.7 STEM CELLS: KEY
CONCEPTS
		INTRODUCTION
		STEM CELL POTENCY
		STEM CELL NICHES
		CONCLUSIONS
		BIBLIOGRAPHY
	SECTION II.2 - Host Reaction to Biomaterials and Their Evaluation
		CHAPTER II.2.1 INTRODUCTION: “BIOLOGICAL RESPONSESTO BIOMATERIALS”
		THE INFLAMMATORY REACTION TO BIOMATERIALS
		SYSTEMIC AND REMOTE EFFECTS
		THROMBOEMBOLIC COMPLICATIONS
		TUMORIGENESIS
		INFECTION
		BIBLIOGRAPHY
		OVERVIEW
		ACUTE INFLAMMATION
		CHRONIC INFLAMMATION
		GRANULATION TISSUE
		FOREIGN-BODY REACTION
		FIBROSIS/FIBROUS ENCAPSULATION
		BIBLIOGRAPHY
		OVERVIEW
		INNATE AND ADAPTIVE IMMUNITY
		COMPONENTS OF INNATE IMMUNITY
		RECOGNITION IN INNATE IMMUNITY
		EFFECTOR MECHANISMS OF INNATE IMMUNITY
		COMPLEMENT
		NEUTROPHILS AND MACROPHAGES: CELLS OF INNATE IMMUNITY
		ADAPTIVE IMMUNITY
		COMPONENTS OF ADAPTIVE IMMUNITY
		ANTIBODIES
		T LYMPHOCYTES
		TH CELLS
		TC CELLS
		RECOGNITION IN ADAPTIVE IMMUNITY
		B CELL AND ANTIBODY RECOGNITION
		T CELL RECOGNITION
		EFFECTOR PATHWAYS IN ADAPTIVE IMMUNITY
		OVERVIEW: IMMUNITY TO PATHOGENS
		PATHOLOGY ASSOCIATED WITH IMMUNE RESPONSES
		PATHOGENESIS OF ANTIBODY-MEDIATED DISEASE
		PATHOGENESIS OF T CELL-MEDIATED DISEASE
		IMMUNE RESPONSES TO TRANSPLANTED TISSUES, BIOMATERIALS, AND SYNTHETIC SUBSTANCES
		BIBLIOGRAPHY
		CHAPTER II.2.4 THE COMPLEMENT
SYSTEM
		INTRODUCTION
		CLASSICAL PATHWAY
		LECTIN PATHWAY
		ALTERNATIVE PATHWAY
		MEMBRANE ATTACK COMPLEX
		CONTROL MECHANISMS
		COMPLEMENT RECEPTORS
		CLINICAL CORRELATES
		SUMMARY AND FUTURE DIRECTIONS
		BIBLIOGRAPHY
		CHAPTER II.2.5 SYSTEMIC TOXICITY
AND HYPERSENSITIVITY
		KINETICS AND THE NATURE OF BIOMATERIALS COMPONENTS
		TOXICO-DYNAMIC CONSIDERATIONS
		METALLIC MATERIALS
		NON-METALLIC BIOMATERIALS
		ADVERSE EFFECTS OF DEFENSE MECHANISMS
		HYPERSENSITIVITY AND IMMUNOTOXICITY
		ALLERGY AND BIOMATERIALS
		TYPES OF ALLERGIES
		TYPE I HYPERSENSITIVITY
		TYPE IV HYPERSENSITIVITY
		ATOPY
		IMMUNOLOGIC TOXICITY OF BIOMATERIALS
		IMPLANT ALLERGY
		OTHER INTERACTIONS
		CONCLUDING REMARKS
		BIBLIOGRAPHY
		CHAPTER II.2.6 BLOOD COAGULATION
AND BLOOD–MATERIALS INTERACTIONS
		PLATELETS
		COAGULATION
		MECHANISMS OF COAGULATION
		CONTROL MECHANISMS
		CONCLUSIONS
		ACKNOWLEDGMENT
		BIBLIOGRAPHY
		CHAPTER II.2.7 TUMORS ASSOCIATED
WITH BIOMATERIALS
AND IMPLANTS
		GENERAL CONCEPTS
		ASSOCIATION OF IMPLANTS WITH HUMAN AND ANIMAL TUMORS
		PATHOBIOLOGY OF FOREIGN-BODY TUMORIGENESIS
		CONCLUSIONS
		BIBLIOGRAPHY
		INTRODUCTION
		BACTERIAL BIOFILMS
		BIOFILM MICROBIOLOGY AND INFECTIOUS DISEASE
		DEVICE-RELATED INFECTION
		CLINICAL EXAMPLES OF BIOFILM INFECTIONS
		PREVENTION AND TREATMENT
		CONCLUSIONS
		BIBLIOGRAPHY
	SECTION II.3 - Biological Testing of Biomaterials
		CHAPTER II.3.1 HOW WELL WILL IT WORK? INTRODUCTION TO TESTING BIOMATERIALS
		BIOCOMPATIBILITY TODAY
		TOXICOLOGY
		THE PRODUCTS OF EXTRINSIC ORGANISMS COLONIZING THE BIOMATERIAL
		MECHANICAL EFFECTS
		CELL–BIOMATERIALS INTERACTIONS
		SUMMARY OF IDEAS TO THIS POINT
		NEW DEVELOPMENTS ARE CHANGING THE PARADIGM OF BIOCOMPATIBILITY
		CONCLUSIONS
		BIBLIOGRAPHY
		INTRODUCTION
		BACKGROUND CONCEPTS
		USE OF MEDICAL DEVICE CHEMICAL COMPOSITION AND MATERIAL EXTRACTS FOR TOXICOLOGICAL RISK ASSESSMENT AND IN VITRO TESTING
		IN VITRO ASSAYS TO ASSESS CELL AND TISSUE COMPATIBILITY IN BIOMATERIAL/MEDICAL DEVICE EVALUATION FOR REGULATORY PURPOSES
		APPLICATION-SPECIFIC IN VITRO ASSAYS CONSIDERED IN PROOF-OF-CONCEPT TESTING
		FUTURE CHALLENGES IN IN VITRO ASSESSMENT OF CELL AND TISSUE COMPATIBILITY
		SUMMARY REMARKS
		BIBLIOGRAPHY
		INTRODUCTION
		SELECTION OF IN VIVO TESTS ACCORDING TO INTENDED USE
		BIOMATERIAL AND DEVICE PERSPECTIVES IN IN VIVO TESTING
		SPECIFIC BIOLOGICAL PROPERTIES ASSESSED BY IN VIVO TESTS
		SELECTION OF ANIMAL MODELS FOR IN VIVO TESTS
		FUTURE PERSPECTIVES ON IN VIVO MEDICAL DEVICE TESTING
		BIBLIOGRAPHY
		ISO STANDARDS
		ASTM INTERNATIONAL, 2008 ANNUAL BOOK OF ASTM STANDARDS, VOLUME 13.01
		BACKGROUND AND PRINCIPLES OF BLOOD–MATERIALS INTERACTIONS ASSESSMENT
		EVALUATION OF BMI
		CONCLUSIONS
		BIBLIOGRAPHY
		INTRODUCTION
		ETHICAL AND REGULATORY OVERVIEW
		INFORMATION RESOURCES
		SURGICAL FACILITY DESIGN
		PREOPERATIVE PREPARATION AND MONITORING
		ANESTHESIA
		ANALGESIA
		SPECIES-SPECIFIC RECOMMENDATIONS
		SUMMARY
		BIBLIOGRAPHY
		INTRODUCTION
		RECOMMENDATIONS FOR PRECLINICAL ASSESSMENT
		CURRENT RECOMMENDATIONS
		RESPONSIBLE USE OF ANIMALS
		ANIMAL MODELS AND SPECIES CONSIDERATION
		EXISTING MODELS
		EXISTING MODELS
		EXISTING MODELS
		TESTING HIERARCHIES
		CURRENT RECOMMENDATIONS AND FUTURE DIRECTIONS
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		MAGNIFICATION, RESOLUTION, AND CONTRAST
		CONFIGURATIONS
		LIGHT MICROSCOPY
		FLUORESCENCE MICROSCOPY
		DIGITAL IMAGING
		ELECTRON MICROSCOPY
		THE REVOLUTION IN OPTICAL MICROSCOPY
		CONCLUSIONS
		BIBLIOGRAPHY
	SECTION II.4 - Degradation of Materials in the Biological Environment
		CHAPTER II.4.1 INTRODUCTION: THEBODY FIGHTS BACK – DEGRADATIONOF MATERIALS IN THE BIOLOGICAL ENVIRONMENT
		CHAPTER II.4.2 CHEMICAL AND BIOCHEMICAL DEGRADATION OF POLYMERSINTENDED TO BEBIOSTABLE
		POLYMER DEGRADATION PROCESSES
		HYDROLYTIC BIODEGRADATION
		OXIDATIVE BIODEGRADATION
		CONCLUSION
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER II.4.3 THE BIODEGRADATION OF BIODEGRADABLE POLYMERIC BIOMATERIALS
		INTRODUCTION
		CHARACTERISTICS OF BIODEGRADABLE POLYMERS
		KINETICS OF BIODEGRADATION
		INFLUENCE OF BIODEGRADATION ON PROPERTIES OF BIODEGRADABLE POLYMERS AND THEIR APPLICATION
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER II.4.4 DEGRADATIVE EFFECTSOF THE BIOLOGICAL ENVIRONMENTON METALS AND CERAMICS
		METALLIC CORROSION
		INFLUENCE OF THE BIOLOGICAL ENVIRONMENT
		CORROSION AND CORROSION CONTROL IN THE BIOLOGICAL ENVIRONMENT
		CERAMIC DEGRADATION
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER II.4.5 PATHOLOGICAL
CALCIFICATION
OF BIOMATERIALS
		INTRODUCTION
		THE SPECTRUM OF PATHOLOGIC BIOMATERIALS AND MEDICAL DEVICE CALCIFICATION
		ASSESSMENT OF BIOMATERIALS CALCIFICATION
		MECHANISMS OF BIOMATERIALS CALCIFICATION
		PREVENTION OF CALCIFICATION
		CONCLUSIONS
		BIBLIOGRAPHY
	SECTION II.5 - Applications of Biomaterials
		CHAPTER II.5.1 INTRODUCTION:
APPLICATIONS
OF BIOMATERIALS
		BIBLIOGRAPHY
		CHAPTER II.5.2 NONTHROMBOGENIC MATERIALS AND STRATEGIES: CASESTUDY
		BIBLIOGRAPHY
		CHAPTER II.5.3 INTRODUCTION TOCARDIOVASCULAR MEDICAL DEVICES
		BIBLIOGRAPHY
		A. SUBSTITUTE HEART VALVES
		INTRODUCTION
		HEART VALVE REPLACEMENT AND REPAIR
		MECHANICAL AND TISSUE VALVE REPLACEMENT DEVICES: TYPES AND COMPLICATIONS
		TRANSCATHETER VALVE REPLACEMENT
		ENGINEERED HEART VALVES
		BIBLIOGRAPHY
		B. ENDOVASCULAR STENTS, VASCULAR GRAFTS, AND STENTGRAFTS
		INTRODUCTION
		ANGIOPLASTY AND STENTS
		VASCULAR GRAFTS
		STENT GRAFTS
		ENGINEERED VASCULAR GRAFTS
		REFERENCES
		C. OTHER CARDIOVASCULAR
DEVICES
		INTRODUCTION
		PACEMAKERS AND ICDS (FOR CARDIAC ARRHYTHMIAS)
		CARDIAC ASSIST AND REPLACEMENT DEVICES (FOR HEART FAILURE)
		MISCELLANEOUS CARDIOVASCULAR DEVICES
		CONCLUSION
		REFERENCES
		D. IMPLANTABLE CARDIAC
ASSIST
DEVICES AND IABPs
		CLINICAL NEED AND APPLICATIONS
		VENTRICULAR ASSIST DEVICE DESIGN AND BLOOD-CONTACTING MATERIALS
		CONCLUSIONS
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER II.5.4 ARTIFICIAL CELLS
		BASIC FEATURES OF ARTIFICIAL CELLS
		RESEARCH INTO THE APPLICATIONS OF ARTIFICIAL CELLS
		ARTIFICIAL CELLS IN HEMOPERFUSION
		NANOBIOTECHNOLOGY FOR PARTIAL ARTIFICIAL RED BLOOD CELLS
		NANOBIOTECHNOLOGY FOR COMPLETE ARTIFICIAL RED BLOOD CELLS
		CELLS, ISLETS, STEM CELLS, GENETICALLY ENGINEERED CELLS, AND MICROORGANISMS
		ARTIFICIAL CELLS CONTAINING STEM CELLS IN REGENERATIVE MEDICINE
		GENE AND ENZYME THERAPY
		DRUG DELIVERY
		OTHER AREAS OF ARTIFICIAL CELLS
		THE FUTURE OF ARTIFICIAL CELLS
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER II.5.5 EXTRACORPOREAL
ARTIFICIAL ORGANS
		INTRODUCTION
		BIBLIOGRAPHY
		CHAPTER II.5.6 ORTHOPEDIC
APPLICATIONS
		INTRODUCTION
		STRUCTURE AND PROPERTIES OF CALCIFIED TISSUES
		BIOMATERIALS DEVELOPMENT: A HISTORY OF TOTAL HIP ARTHROPLASTY
		NEW DEVELOPMENTS: TOTAL DISC ARTHROPLASTY
		CURRENT BIOMATERIALS IN TOTAL ARTHROPLASTY
		NEW ALLOYS AND SURFACE COATINGS
		ORTHOPEDIC BIOMATERIALS: CLINICAL CONCERNS
		BIBLIOGRAPHY
		CHAPTER II.5.7 DENTAL IMPLANTATION
		PATIENT PROFILES, DENTAL NEEDS, AND SURGICAL IMPLANTS: 1950S–2010S
		ANATOMICAL AND IMAGING CONSIDERATIONS
		BIOMATERIALS
		TISSUE INTEGRATION: BIOMATERIAL AND BIOMECHANICAL ASPECTS
		BIBLIOGRAPHY
		CHAPTER II.5.8 ADHESIVES AND
SEALANTS
		INTRODUCTION
		THE LOGIC OF ADHESION PROCEDURES
		ADHEREND SURFACE PRETREATMENTS TO ENHANCE BOND STRENGTH AND DURABILITY
		HARD TISSUE ADHESIVES: BONE AND TOOTH CEMENTS
		GLOSSARY OF TERMS
		BIBLIOGRAPHY
		CHAPTER II.5.9 OPHTHALMOLOGIC
APPLICATIONS: INTRODUCTION
		OVERVIEW OF EYE ANATOMY
		EYE-RELATED CONDITIONS AND STATISTICS
		BIBLIOGRAPHY
		A. BIOMATERIALS: CONTACT LENSES
		CONTACT LENS MATERIALS
		SURFACE MODIFICATIONS
		SPECIALTY LENSES
		CONTACT LENS SOLUTIONS
		BIBLIOGRAPHY
		B. INTRAOCULAR LENS IMPLANTS:
A SCIENTIFIC PERSPECTIVE
		INTRODUCTION TO INTRAOCULAR LENS IMPLANTS, THE OPTICS OF THE EYE AND CATARACTS
		WHY ARE IOLS SUCCESSFUL?
		EMERGING FUNCTIONAL VARIATIONS OF IOLS
		BIOMATERIALS FOR IOLS
		IOLS WITH VARIATIONS OF OPTICAL FUNCTION
		OVERALL SUMMARY AND FUTURE OF IOLS
		BIBLIOGRAPHY
		C. CORNEAL INLAYS AND ONLAYS
		HISTORY OF CORNEAL INLAYS AND ONLAYS
		SYNTHETIC BIOMATERIALS IN THE CORNEA
		OPTICAL REQUIREMENTS
		BIOLOGICAL REQUIREMENTS
		COMMERCIAL ATTEMPTS AT SYNTHETIC CORNEAL INLAYS AND ONLAYS
		PERMEABLE INTRACORNEAL LENSES
		IMPERMEABLE INTRACORNEAL LENSES
		SYNTHETIC MATERIALS FOR CORNEAL ONLAYS
		CORNEAL INLAYS AND ONLAYS TODAY
		THE FUTURE OF CORNEAL INLAYS AND ONLAYS
		BIBLIOGRAPHY
		D. OPHTHALMOLOGIC APPLICATIONS:
GLAUCOMA DRAINS AND IMPLANTS
		HISTORICAL PERSPECTIVE ON THE TREATMENT OF GLAUCOMA
		NEW DRAINAGE DEVICES AND MATERIALS UNDER DEVELOPMENT
		SUMMARY
		REFERENCES
		E. THE DEVELOPMENT OF A RETINALPROSTHESIS: A SIGNIFICANT BIOMATERIALS CHALLENGE
		INTRODUCTION
		OVERVIEW OF THE VISUAL SYSTEM
		RETINAL PROSTHESES
		OTHER MATERIALS CONCERNS
		DIRECTIONS FOR THE FUTURE
		SUMMARY
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER II.5.10 BIOELECTRODES
		INTRODUCTION
		ELECTRODE–ELECTROLYTE INTERFACE
		EQUIVALENT CIRCUIT MODELS
		FACTORS INFLUENCING MATERIAL SELECTION
		ELECTRODE MATERIALS
		APPLICATIONS
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER II.5.11 COCHLEAR
PROSTHESES
		INTRODUCTION
		OVERVIEW OF THE AUDITORY SYSTEM
		COCHLEAR PROSTHESES
		MATERIALS AND ELECTRODE ARRAYS
		FUTURE DIRECTIONS
		SUMMARY
		ACKNOWLEDGMENTS
		GLOSSARY OF TERMS
		BIBLIOGRAPHY
		CHAPTER II.5.12 THE ROLE OFBIOMATERIALS IN STIMULATING BIOELECTRODES
		INTRODUCTION
		NEUROSTIMULATION
		FUNDAMENTAL REQUIREMENTS OF A BIOELECTRODE
		PRINCIPLES OF CHARGE INJECTION
		ACTIVE CHEMICAL PROCESSES AND ELECTROCHEMICAL REVERSAL
		PASSIVE CHEMICAL PROCESSES AND MECHANICAL INTERACTION OF ELECTRODE AND TISSUE
		NEUROSTIMULATION APPLICATIONS
		FUTURE DIRECTIONS
		BIBLIOGRAPHY
		CHAPTER II.5.13 MEDICAL
BIOSENSORS
		INTRODUCTION
		BASICS OF BIOSENSING
		CHALLENGES IN BIOSENSING
		BIOFOULING PREVENTION METHODS
		EFFECTS OF BIOFOULING ON SAMPLE REMOVAL SYSTEMS
		POINT-OF-CARE MEASUREMENTS ENABLING DISTRIBUTED DIAGNOSIS AND HOME HEALTHCARE
		SUMMARY
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER II.5.14 BURN DRESSINGS
AND SKIN SUBSTITUTES
		SKIN: THE LARGEST ORGAN
		SKIN SUBSTITUTES
		COMPOSITE AUTOLOGOUS TISSUE AND SKIN TRANSFER
		COMBINED THERAPY WITH VACUUM ASSISTED CLOSURE (VAC)
		THE MARKETPLACE FOR BURN DRESSINGS AND SKIN SUBSTITUTES
		BIBLIOGRAPHY
		CHAPTER II.5.15 SUTURES
		GENESIS AND COMMON USES
		DESCRIPTION OF SURGICAL SUTURE
		MANUFACTURING PROCESSAND INTENDED USE
		PERFORMANCE EVALUATION
		REGULATORY CONSIDERATIONS
		NEWER TRENDS AND FUTURE DEVELOPMENT
		BIBLIOGRAPHY
		CHAPTER II.5.16 DRUG DELIVERYSYSTEMS
		A. INTRODUCTION
		INTRODUCTION: PRINCIPLES, ORIGINS, AND EVOLUTION OF CONTROLLED DRUG DELIVERY SYSTEMS (CDDS)
		BIBLIOGRAPHY
		B. INJECTED NANOCARRIERS
		B.1. INTRODUCTION
		BIBLIOGRAPHY
		B.2. PEGYLATION OF DRUGS ANDNANOCARRIERS
		BIBLIOGRAPHY
		B.3. TARGETING
		INTRODUCTION
		IMMUNOTARGETING
		CARBOHYDRATES
		NUTRIENT-BASED TARGETING
		PEPTIDE-BASED TARGETING
		SUMMARY
		BIBLIOGRAPHY
		B.4. POLYMER–DRUG CONJUGATES
		INTRODUCTION
		POLY(HPMA) AS A DRUG CARRIER
		POLY(GLUTAMIC ACID) (PG) AS A DRUG CARRIER
		CYCLODEXTRIN POLYMERS AS DRUG CARRIERS
		POLYACETALS AS DRUG CARRIERS
		BIBLIOGRAPHY
		B.5. LIPOSOMES
		BIBLIOGRAPHY
		B.6. POLYMERIC MICELLES
		INTRODUCTION
		BIBLIOGRAPHY
		B.7. Dendrimers
		BIBLIOGRAPHY
		B.8. NUCLEIC ACID DELIVERY
		INTRODUCTION
		GENE EXPRESSION
		GENE KNOCKDOWN
		LIGAND BINDING
		BIOMATERIALS AND NUCLEIC ACID DELIVERY
		VIRAL DELIVERY
		NON-VIRAL DELIVERY: INTRODUCTION
		LOCAL GENE DELIVERY
		EXTRACELLULAR REQUIREMENTS FOR EFFICIENT NUCLEIC ACID DELIVERY
		INTRACELLULAR REQUIREMENTS FOR EFFICIENT NUCLEIC ACID DELIVERY
		ESCAPING FROM THE ENDOSOME
		NUCLEAR ENTRY AND DELIVERY
		BIBLIOGRAPHY
		B.9. POLYMERIC AND ALBUMINATED
DRUG NANOPARTICLES
		BIBLIOGRAPHY
		C. INJECTED DEPOT DDS
		INJECTED DEPOT SYSTEMS
		BIBLIOGRAPHY
		D. IMPLANTS AND INSERTS
		INTRODUCTION
		IMPLANTS
		PUMP-BASED DDS
		INFUSION PUMPS
		INSERTS
		THE FUTURE
		BIBLIOGRAPHY
		E. SMART DDS
		ENVIRONMENTALLY-RESPONSIVE SYSTEMS
		REFERENCES
		F. TRANSDERMAL DDS
		INTRODUCTION
		PASSIVE TRANSDERMAL DELIVERY SYSTEMS (PASSIVE TDDS)
		ACTIVE TRANSDERMAL DELIVERY SYSTEMS (ACTIVE TDDS)
		GLOSSARY
		BIBLIOGRAPHY
		G. ORAL DRUG DELIVERY
		FEATURES OF THE GASTROINTESTINAL TRACT
		CONTROLLED RELEASE IN THE GI TRACT
		BIBLIOGRAPHY
		CHAPTER II.5.17 DIAGNOSTIC
APPLICATIONS
OF BIOMATERIALS
		OVERVIEW OF DIAGNOSTICS
		THE PRE-ANALYTICAL PHASE
		THE ANALYTICAL PHASE
		INTERPRETATION
		SUMMARY
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		CHAPTER II.5.18 MEDICAL APPLICATIONS OF SILICONES
		MEDICAL APPLICATIONS
		BIOCOMPATIBILITY
		BIODURABILITY
		CONCLUSION
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
	SECTION II.6 - Applications of Biomaterials in Functional Tissue Engineering
		CHAPTER II.6.1 INTRODUCTION: REBUILDING HUMANS USING BIOLOGY AND BIOMATERIALS
		BIBLIOGRAPHY
		CHAPTER II.6.2 OVERVIEW OF TISSUE ENGINEERING CONCEPTS AND APPLICATIONS
		GENERAL INTRODUCTION
		GOALS OF TISSUE ENGINEERING AND CLASSIFICATION
		COMPONENTS OF TISSUE ENGINEERING
		MATERIALS
		SCAFFOLD DESIGN
		DEVELOPMENT OF TISSUE ENGINEERING CONSTRUCTS
		MODELS FOR TISSUE ENGINEERING
		APPLICATIONS OF TISSUE ENGINEERING
		CURRENT CHALLENGES AND FUTURE DIRECTIONS
		FUTURE PERSPECTIVES
		BIBLIOGRAPHY
		CHAPTER II.6.3 TISSUE ENGINEERING SCAFFOLDS
		SCAFFOLD DESIGN
		SCAFFOLD MATERIALS
		APPLICATIONS OF SCAFFOLDS
		SCAFFOLD PROCESSING TECHNIQUES
		CHARACTERIZATION OF PROCESSED SCAFFOLDS
		CELL SEEDING AND CULTURE IN THREE-DIMENSIONAL SCAFFOLDS
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER II.6.4 CELL SOURCES FORTISSUEENGINEERING: MESENCHYMAL STEM CELLS
		INTRODUCTION
		MESENCHYMAL STEM CELLS
		MSC-NICHE
		OTHER SOURCES OF MSCS
		A NEW ERA OF MSC-BASED THERAPIES
		LONG-TERM GOALS
		SYNOPSIS
		ACKNOWLEDGMENTS
		BIBLIOGRAPHY
		INTRODUCTION
		MICROMECHANICAL CONTROL OF TISSUE FORM AND FUNCTION
		MICROSCALE DESIGN OF BIOMIMETIC SCAFFOLDS FOR TISSUE RECONSTRUCTION
		CELL AND ECM MECHANICS AS KEY REGULATORS OF TISSUE DEVELOPMENT
		BIOMATERIALS FOR STEM CELL DEVELOPMENT AND TISSUE REGENERATION
		MOLECULAR MECHANISMS OF CELLULAR MECHANOTRANSDUCTION
		IMPLICATIONS FOR FUTURE MATERIALS DESIGN FOR IN SITU TISSUE ENGINEERING
		CONCLUSION
		ACKNOWLEDGEMENTS
		BIBLIOGRAPHY
		CHAPTER II.6.6 BIOREACTORS
FOR TISSUE ENGINEERING
		INTRODUCTION
		BIOREACTOR DESIGN CONSIDERATIONS
		CARTILAGE TISSUE ENGINEERING WITH MECHANICAL LOADING
		TISSUE ENGINEERING OF ANATOMICALLY-SHAPED HUMAN BONE
		CARDIAC TISSUE ENGINEERING WITH MECHANICAL STRETCH
		CARDIAC TISSUE ENGINEERING WITH ELECTRICAL STIMULATION AND MEDIUM PERFUSION
		TISSUE ENGINEERING OF HEART VALVES WITH MECHANICAL STIMULATION AND PERFUSION
		TISSUE ENGINEERING OF BLOOD VESSELS WITH PULSATILE MEDIUM FLOW
		CHALLENGES IN BIOREACTOR DESIGN
		WORKED EXAMPLES
		ACKNOWLEDGMENT
		BIBLIOGRAPHY
		CHAPTER II.6.7 BONE TISSUE
ENGINEERING
		INTRODUCTION
		BONE BIOLOGY
		CELLS INVOLVED
		BONE TISSUE DEVELOPMENT
		BONE GRAFTS
		BONE GRAFT SUBSTITUTES
		POROSITY IN BONE GRAFT SUBSTITUTES
		DIMENSION IN BONE GRAFT SUBSTITUTES
		IN VITRO CULTURE TECHNIQUES FOR BONE GRAFT SUBSTITUTES
		CONCLUSION
		BIBLIOGRAPHY
		INTRODUCTION TO CARTILAGE AND LIGAMENT TISSUE ENGINEERING
		CARTILAGE TISSUE ENGINEERING
		LIGAMENT TISSUE ENGINEERING
		ACKNOWLEDGMENT
		BIBLIOGRAPHY
		CHAPTER II.6.9 BLOOD VESSEL TISSUE
ENGINEERING
		INTRODUCTION
		ENABLING TECHNOLOGIES
		TISSUE ENGINEERING APPROACHES
		CONCLUDING DISCUSSION
		BIBLIOGRAPHY
		CHAPTER II.6.10 HEART VALVE TISSUE
ENGINEERING
		DESIGN CRITERIA AND CHALLENGES IN TISSUE-ENGINEERED HEART VALVE (TEHV)
		TISSUE ENGINEERING APPROACHES TO HEART VALVES
		CHALLENGES FOR FUTURE TRANSLATION OF ENGINEERED TISSUE VALVES TO THE CLINIC
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER II.6.11 CARDIAC MUSCLE
TISSUE ENGINEERING
		INTRODUCTION
		CARDIOVASCULAR DISEASE AND THE NEED FOR ENGINEERED MYOCARDIUM
		CONSIDERATIONS FOR ENGINEERING CARDIAC MUSCLE
		SOME REPRESENTATIVE STUDIES IN CARDIAC TISSUE ENGINEERING
		CHALLENGES AND FUTURE APPLICATIONS
		WORKED EXAMPLE
		SOLUTION
		ACKNOWLEDGMENT
		BIBLIOGRAPHY
		CHAPTER II.6.12 TISSUE-ENGINEEREDSKIN SUBSTITUTES
		INTRODUCTION
		TYPES OF SKIN SUBSTITUTES
		COMMERCIAL PRODUCTION OF SKIN SUBSTITUTES
		THE TRANSCYTE® SYSTEM
		CONCLUSION
		BIBLIOGRAPHY
		CHAPTER II.6.13 ESOPHAGEAL AND GASTROINTESTINAL TISSUE ENGINEERING
		INTRODUCTION
		ANATOMY AND STRUCTURE
		TISSUE ENGINEERING OF GI TISSUES
		BIBLIOGRAPHY
		CHAPTER II.6.14 NEURONAL TISSUEENGINEERING
		CHALLENGES TO NEURAL TISSUEHEALING AND THE ENABLING THERAPEUTIC ROLE OF BIOMATERIALS
		BIOMATERIALS-BASED CUES FORTHE TREATMENT OF NEURAL INJURY/DISEASE
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER II.6.15 IMMUNOISOLATION
		INTRODUCTION
		PRINCIPLES OF IMMUNOISOLATION
		DEVICES FOR IMMUNOISOLATION
		ENCAPSULATED CELL THERAPY APPLICATIONS
		CONCLUDING PERSPECTIVES
		BIBLIOGRAPHY
		CHAPTER II.6.16 TISSUE ENGINEERING
WITH DECELLULARIZED TISSUES
		INTRODUCTION
		RATIONALE FOR THE DECELLULARIZATION OF TISSUES AND ORGANS AND THE USE OF DECELLULARIZED TISSUES AS SCAFFOLDS IN TISSUE ENGINEERI...
		METHODS OF DECELLULARIZATION
		ECM CONFIGURATION
		MECHANISMS BY WHICH ECM SCAFFOLDS FUNCTION AS INDUCTIVE TEMPLATES FOR TISSUE RECONSTRUCTION
		CONCLUSION
		BIBLIOGRAPHY
PART III - Practical Aspects of Biomaterials
	SECTION III.1 - Implants, Devices, and Biomaterials: Special Considerations
		CHAPTER III.1.1 INTRODUCTION:IMPLANTS, DEVICES, ANDBIOMATERIALS: SPECIALCONSIDERATIONS
		BIBLIOGRAPHY
		CHAPTER III.1.2 STERILIZATION
OF IMPLANTS AND DEVICES
		INTRODUCTION
		STERILIZATION TECHNOLOGIES
		MATERIAL COMPATIBILITY
		STERILITY AND PATIENT SAFETY
		PRODUCT AND PATIENT SAFETY ISSUES
		TERMINAL STERILIZATION VALIDATION PRINCIPLES
		SUMMARY AND FUTURE CHALLENGES
		BIBLIOGRAPHY
		CHAPTER III.1.3 CORRELATION, MATERIALS PROPERTIES, STATISTICS AND BIOMATERIALS SCIEN
		INTRODUCTION
		BIOCOMPATIBILITY AND MEDICAL DEVICE PERFORMANCE
		DATA, INFORMATION, AND STATISTICS
		CORRELATION
		ASPECTS OF THE BIOREACTION TO BIOMATERIALS
		THE CASE FOR CORRELATION: A BRIEF REVIEW OF THE LITERATURE
		ISSUES COMPLICATING SIMPLE CORRELATION
		MULTIVARIATE CORRELATION
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER III.1.4 DEVICE FAILUREMODE ANALYSIS
		ROLE OF BIOMATERIALS–TISSUE INTERACTIONS: EFFECT OF MATERIALS ON THE PATIENT AND THE EFFECT OF THE PATIENT ON THE MATERIALS
		TESTING OF BIOMATERIALS–DESIGN CONFIGURATIONS
		BIOLOGICAL TESTING OF IMPLANTS
		RAW MATERIALS, FABRICATION, AND STERILIZATION
		PACKAGING, SHIPPING, AND STORAGE
		CLINICAL HANDLING AND SURGICAL PROCEDURE
		THE RECIPIENT
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER III.1.5 IMPLANT RETRIEVAL AND EVALUATION
		INTRODUCTION
		GOALS
		COMPONENTS OF IMPLANT RETRIEVAL AND EVALUATION
		APPROACH TO ASSESSMENT OF HOST AND IMPLANT RESPONSES
		THE ROLE OF IMPLANT RETRIEVAL IN DEVICE DEVELOPMENT
		WHAT CLINICALLY USEFUL INFORMATION HAS BEEN LEARNED FROM IMPLANT RETRIEVAL AND ANALYSIS?
		CONCLUSIONS
		BIBLIOGRAPHY
		GENERAL REFERENCES
	SECTION III.2 - Voluntary Standards, Regulatory Compliance, and Non-Technical Issues
		CHAPTER III.2.1 INTRODUCTION:VOLUNTARYSTANDARDS, REGULATORY COMPLIANCE, ANDOTHER NON-TECHNICAL ISSUES
		BIBLIOGRAPHY
		CHAPTER III.2.2 COMMERCIALIZATION: WHAT IT TAKES TO GET A PRODUCT TO MARKET
		INTRODUCTION
		THE NEED YOU PROPOSE TO SOLVE
		MARKET SIZE AND GROWTH
		EFFECT ON VARIOUS CONSTITUENCIES
		CLINICAL TRIALS
		BUSINESS AND COMMERCIALIZATION ISSUES
		THE STAGES OF LIFE SCIENCE: FROM CONCEPT TO ADOPTION
		BIBLIOGRAPHY
		WHO USES STANDARDS?
		WHO WRITES STANDARDS?
		BIOCOMPATIBILITY STANDARDS
		TISSUE-ENGINEERED MEDICAL PRODUCTS
		NANOTECHNOLOGY
		WORKSHOP AND SYMPOSIA
		INTERNATIONALIZATION OF STANDARDS
		GLOBAL REGULATORY STRATEGY ACCORDING TO INTENDED USE
		DESIGN CONTROL AND RISK ANALYSIS
		BIOCOMPATIBILITY ASSESSMENT FOR BIOMATERIALS IN MEDICAL DEVICES
		MANUFACTURING CONTROLS AND POST-MARKET OVERSIGHT
		PREMARKET CLEARANCE (510(K)), PREMARKET APPROVAL (PMA) OR “CE MARK”
		CLINICAL AND ANIMAL TRIALS OF UNAPPROVED DEVICES
		STERILIZATION, SHELF-LIFE, AND AGING
		INNOVATIVE TECHNOLOGIES REQUIRE SPECIAL CONSIDERATIONS
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER III.2.5 PRINCIPLES OF REIMBURSEMENT FOR MEDICAL DEVICES
		SIGNIFICANCE OF REIMBURSEMENT
		BACKGROUND
		POINTS OF SERVICE
		THE “HOSPITAL BILL” AND THE “CLAIM”
		CLAIMS PROCESSING
		PAYMENT
		COVERAGE
		CHAPTER III.2.6 CORPORATE CONSIDERATIONS ON BIOMATERIALS AND MEDICAL DEVICES: CASE STUDIESIN REGULATION AND REIMBURSEMENT
		CLAIMS DATABASES
		REGULATORY STRATEGY
		MEDICARE REIMBURSEMENT
		DESIGN CONTROLS
		MANUFACTURING CONTROLS
		REGISTRATION, LISTING, AND INSPECTION
		INTELLECTUAL PROPERTY
		FURTHER READING
		BIBLIOGRAPHY
		CHAPTER III.2.7 ETHICAL ISSUES IN BIOMATERIALS AND MEDICAL DEVICES
		INTRODUCTION
		PROTECTION OF PATIENTS
		GOOD LABORATORY PRACTICE
		GOOD MANUFACTURING PRACTICE
		GOOD CLINICAL PRACTICE
		PROTECTION OF RESEARCH SUBJECTS
		CONFLICTS OF INTEREST
		CONCLUSION
		A PRACTICAL EXAMPLE: THE DESIGN OF A NOVEL HEART VALVE
		BIBLIOGRAPHY
		CHAPTER III.2.8 LEGAL ASPECTSOF BIOMATERIALS
		INTRODUCTION
		INTRAUTERINE DEVICES
		PEDICLE SCREWS
		SILICONE BREAST IMPLANTS
		IMPLANTABLE CARDIAC DEFIBRILLATORS
		ARTIFICIAL HEART VALVES
		HIP/KNEE PROSTHESIS IMPLANTS
		PREEMPTION
		SCIENCE IN THE COURTROOM
		BIOMATERIALS ACCESS INSURANCE ACT
		LIABILITY OF THE DESIGN ENGINEER
		DEVICE MARKETING AND PROMOTION
		DEFENSIVE MANUFACTURING AND MARKETING
		CONCLUSION
		BIBLIOGRAPHY
		CHAPTER III.2.9 CLINICAL TRIALS
FOR MEDICAL DEVICES
		INTRODUCTION
		THE FIRST SUCCESSFUL HEART VALVE PROSTHESIS
		CRITIQUE OF MEDICAL DEVICE RCTS
		MEDICAL DEVICE REGULATORY TRIALS
		IMPROVING OBSERVATIONAL STUDIES
		ADAPTIVE AND BAYESIAN TRIALS
		CLINICAL TRIALS FOR TRANSCATHETER VALVES
		SUMMARY
		BIBLIOGRAPHY
		CHAPTER III.2.10 ENTREPRENEURSHIP
IN BIOMATERIALS
		INTRODUCTION
		THE ENTREPRENEURIAL ECOSYSTEM AND THE START-UP PROCESS
		BUILDING A SUCCESSFUL START-UP
		CONCLUSIONS
		BIBLIOGRAPHY
		CHAPTER III.2.11 POSTMARKET CONSIDERATIONS IN BIOMATERIALS AND MEDICAL DEVICES
		THE FDA’s POSTMARKETING PROGRAMS
		PASSIVE EVENT SURVEILLANCE: SPONTANEOUS REPORTS
		BIOMATERIALS AND MEDWATCH
		ACTIVE EVENT SURVEILLANCE
		FDA TRACKING AND CLINICAL TRIAL REQUIREMENTS
		NEW FDA DEVICE SAFETY INITIATIVES
		SUMMARY: WHAT DOES POSTMARKETING SURVEILLANCE TEACH US?
		BIBLIOGRAPHY
Appendices
	APPENDIX
A - Properties of Biological Fluids
	APPENDIX
B - Properties of Soft Materials
		BIBLIOGRAPHY
	APPENDIX
C
	APPENDIX
D - The Biomaterials Literature
Index