Biomaterials Science

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

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

Part 1: 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

Bibliography

Chapter I.1.3. Bulk Properties of Materials

Introduction

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

bibliography

Chapter I.1.4. Finite Element Analysis in Biomechanics

Introduction

Overview of the Finite Element Method

Conclusion

Bibliography

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 Water in Biomaterials

Water: The Special Molecule

Water: Structure

Water: Significance for Biomaterials

Bibliography

Section I.2: Classes of Materials Used in Medicine

Chapter I.2.1. Introduction: The Diversity and Versatility of Biomaterials

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

Concluding Remarks

Bibliography

B. Silicones

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

Chapter I.2.4. Ceramics, Glasses, and Glass-Ceramics: Basic Principles

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

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

Short-Fiber Composites

Particulate Composites

Glossary of Terms

Bibliography

Chapter I.2.10. Non-Fouling Surfaces

Introduction

Background

Conclusions and Perspectives

Bibliography

Chapter I.2.11. Applications of “Smart Polymers” as Biomaterials

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

Chapter I.2.12. Physicochemical Surface Modification of Materials Used in Medicine

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 2: Biology and Medicine

Section II.1: Some Background Concepts

Chapter II.1.1. Introduction: Biology and Medicine – Key Concepts in the Use of Biomaterials in Surgery and 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

Cells: Function and Response to Injury

Tissues and the Extracellular Matrix

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, the Extracellular Matrix, and Cell–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

Chapter II.1.6. Effects of Mechanical Forces on Cells and Tissues (The Liquid–Cell Interface)

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 Responses to Biomaterials”

The Inflammatory Reaction to Biomaterials

Systemic and Remote Effects

Thromboembolic Complications

Tumorigenesis

Infection

Bibliography

Chapter II.2.2. Inflammation, Wound Healing, and the Foreign-Body Response

Overview

Acute Inflammation

Chronic Inflammation

Granulation Tissue

Foreign-Body Reaction

Fibrosis/Fibrous Encapsulation

Bibliography

Chapter II.2.3. Innate and Adaptive Immunity: The Immune Response to Foreign Materials

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

Chapter II.2.8. Biofilms, Biomaterials, and Device-Related Infections

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

Chapter II.3.2. The Concept and Assessment of Biocompatibility

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

Chapter II.3.3. In Vitro Assessment of Cell and Tissue Compatibility

Introduction

Background Concepts

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

Chapter II.3.4. In Vivo Assessment of Tissue Compatibility

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

Chapter II.3.5. Evaluation of Blood–Materials Interactions

Introduction

Background and Principles of Blood–Materials Interactions Assessment

Evaluation of BMI

Conclusions

Bibliography

Chapter II.3.6. Animal Surgery and Care of Animals

Introduction

Ethical And Regulatory Overview

Information Resources

Surgical Facility Design

Preoperative Preparation and Monitoring

Anesthesia

Analgesia

Species-Specific Recommendations

Summary

bibliography

Chapter II.3.7. Large Animal Models in Cardiac and Vascular Biomaterials Research and Assessment

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

Chapter II.3.8. Microscopy for Biomaterials Science

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: The Body Fights Back – Degradation of Materials in the Biological Environment

Chapter II.4.2. Chemical and Biochemical Degradation of Polymers Intended to be Biostable

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 Effects of the Biological Environment on 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: Case Study

Bibliography

Chapter II.5.3. Introduction to Cardiovascular Medical Devices

Bibliography

A. Substitute Heart Valves

Introduction

Heart Valve Function and Dysfunction

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 Stent Grafts

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

Orthopedic Biomaterials Market

Orthopedic Biomaterials

Orthopedic Biomaterials Design

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

Introduction

General Properties and Corneal Requirements

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 Retinal Prosthesis: 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 of Biomaterials 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 Process and Intended Use

Performance Evaluation

Regulatory Considerations

Newer Trends and Future Development

Alternatives to Suture

Bibliography

Chapter II.5.16. Drug Delivery Systems

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 and Nanocarriers

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 for Tissue Engineering: 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

Chapter II.6.5. Micromechanical Design Criteria for Tissue Engineering Biomaterials

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

Chapter II.6.8. Cartilage and Ligament Tissue Engineering: Biomaterials, Cellular Interactions, and Regenerative Strategies

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-Engineered Skin 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 Tissue Engineering

Challenges to Neural Tissue Healing and the Enabling Therapeutic Role of Biomaterials

Biomaterials-Based Cues for the 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 Engineering and Regenerative Medicine

Methods of Decellularization

ECM Configuration

Composition of Extracellular Matrix

Mechanisms by Which ECM Scaffolds Function as Inductive Templates for Tissue Reconstruction

Host Cell and Immune Responses to Implanted ECM Scaffolds

Potential Immune Activating Molecules within ECM Scaffolds

Innate Immune Response to ECM Scaffolds

T-Cell-Mediated Immune Response to ECM Scaffolds

Angiogenesis and New ECM Deposition

Response to Mechanical Stimuli

Conclusion

Bibliography

Part 3: Practical Aspects of Biomaterials

SECTION III.1: Implants, Devices, and Biomaterials: Special Considerations

Chapter III.1.1 Introduction: Implants, Devices, and Biomaterials: Special Considerations

Bibliography

Chapter III.1.2. Sterilization of Implants and Devices

Introduction

Sterilization Technologies

Material Compatibility

Optimizing Chances for Finding Material Compatibility Solutions

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 Science

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 Failure Mode 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: Voluntary Standards, Regulatory Compliance, and Other 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

Chapter III.2.3. Voluntary Consensus Standards

What are Standards?

Who uses Standards?

Who writes Standards?

Biocompatibility Standards

Tissue-Engineered Medical Products

Nanotechnology

Workshop and Symposia

Internationalization of Standards

Chapter III.2.4. Regulatory Overview for Medical Products Using Biomaterials

Introduction

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

Claims Databases

Chapter III.2.6. Corporate Considerations on Biomaterials and Medical Devices: Case Studies in Regulation and Reimbursement

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 Aspects of 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

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

Appendix A: Properties of Biological Fluids

Appendix B: Properties of Soft Materials

Bibliography

Appendix C

Appendix D: The Biomaterials Literature

Biomaterials Journals (or Journals with Significant Biomaterials Content)

Biomaterials Books

Index