Comprehensive Biomaterials - 1st Edition - ISBN: 9780080553023, 9780080552941

Comprehensive Biomaterials

1st Edition

Editors: Paul Ducheyne Paul Ducheyne Kevin Healy Dietmar E. Hutmacher David W. Grainger C. James Kirkpatrick
eBook ISBN: 9780080552941
Hardcover ISBN: 9780080553023
Imprint: Elsevier Science
Published Date: 24th August 2011
Page Count: 3672
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Comprehensive Biomaterials brings together the myriad facets of biomaterials into one, major series of six edited volumes that would cover the field of biomaterials in a major, extensive fashion: 

Volume 1: Metallic, Ceramic and Polymeric Biomaterials
Volume 2: Biologically Inspired and Biomolecular Materials
Volume 3: Methods of Analysis
Volume 4: Biocompatibility, Surface Engineering, and Delivery Of Drugs, Genes and Other Molecules
Volume 5: Tissue and Organ Engineering
Volume 6: Biomaterials and Clinical Use

Experts from around the world in hundreds of related biomaterials areas have contributed to this publication, resulting in a continuum of rich information appropriate for many audiences. The work addresses the current status of nearly all biomaterials in the field, their strengths and weaknesses, their future prospects, appropriate analytical methods and testing, device applications and performance, emerging candidate materials as competitors and disruptive technologies, and strategic insights for those entering and operational in diverse biomaterials applications, research and development, regulatory management, and commercial aspects. From the outset, the goal was to review materials in the context of medical devices and tissue properties, biocompatibility and surface analysis, tissue engineering and controlled release. It was also the intent both, to focus on material properties from the perspectives of therapeutic and diagnostic use, and to address questions relevant to state-of-the-art research endeavors.

Key Features

  • Reviews the current status of nearly all biomaterials in the field by analyzing their strengths and weaknesses, performance as well as future prospects
  • Presents appropriate analytical methods and testing procedures in addition to potential device applications
  • Provides strategic insights for those working on diverse application areas such as R&D, regulatory management, and commercial development


This work is of interest to any student, researcher or engineer working in biomaterials, medicinal research, cell biology, tissue engineering, tissue physiology, regenerative medicine, microfabrication, and biomedical devices and applications

Table of Contents



Editor-in-Chief Biography

Co-Editor Biographies



Permission Acknowledgments

1.101. Biomaterials

1.102. Metals for Use in Medicine


1.102.1. Introduction

1.102.2. General Requirements for Long-Term Implantation

1.102.3. Key Metallurgy Concepts

1.102.4. Chemical Composition and Structure

1.102.5. Mechanical Properties

1.102.6. Processing Effects

1.102.7. Future Developments

1.102.8. Summary

1.103. Electrochemical Behavior of Metals in the Biological Milieu



1.103.1. Introduction

1.103.2. Metals Currently Used in Medical Devices

1.103.3. Metallic Biocompatibility

1.103.4. The Biological Milieu

1.103.5. Basic Electrochemistry Concepts

1.103.6. Passive Oxide Films and Semiconducting Electrochemistry

1.103.7. Electrical Double Layer

1.103.8. Electrochemical Impedance Spectroscopy (EIS) of Metallic Biomaterials

1.103.9. Mechanically Assisted Corrosion

1.103.10. Effects of Prior Electrochemical History

1.103.11. Oxide Film Structure and Formation

1.103.12. Effects of Solution Redox System

1.103.13. Biological Consequences: Oxidation and Reduction

1.103.14. Summary

1.103.15. Appendix: Derivation of Mott–Schottky Equation

1.104. Shape Memory Alloys for Use in Medicine


1.104.1. Introduction

1.104.2. Fundamentals of Shape Memory Systems

1.104.3. Practical SMAs

1.104.4. Manufacturing, Processing, and Performance of Nitinol

1.104.5. Minimally Invasive Device Applications for Nitinol

1.104.6. Orthodontic Applications for Nitinol

1.104.7. Orthopedic Applications for Nitinol

1.104.8. Clinical Imaging of Nitinol Medical Devices

1.104.9. Long-Term Durability and Biocompatibility of Nitinol

1.104.10. Summary and Future Directions

1.105. Alumina


1.105.1. Introduction

1.105.2. Properties of Alumina

1.105.3. Clinical Application of Alumina Ceramics

1.106. Zirconia as a Biomaterial


1.106.1. Introduction

1.106.2. Crystallography and Phase Transformation of Zirconia

1.106.3. Different Types of Zirconia and Zirconia-Based Composites

1.106.4. The Use of Zirconia as a Biomaterial: Current State of the Art

1.106.5. Future Directions

1.106.6. Conclusion

1.106.7. Further Reading

1.107. Carbon and Diamond


1.107.1. Introduction

1.107.2. Pyrolytic Carbon

1.107.3. Diamond-Like Carbon

1.107.4. Microcrystalline, Nanocrystalline, and Ultrananocrystalline Diamond

1.107.5. Summary of Carbon and Diamond

1.108. Wear-Resistant Ceramic Films and Coatings


1.108.1. Introduction

1.108.2. State of the Art – Processing, Microstructure, Biocompatibility, and Mechanical Properties of Ceramic Coatings

1.108.3. Future Trends

1.109. Bioactive Ceramics


1.109.1. Bioactivity

1.109.2. Bone Formation at the Interface with Bioactive Materials

1.109.3. Testing Bioactivity In Vitro

1.109.4. Methods of Analysis of the Dissolution–Precipitation Reaction

1.109.5. Bioactive Glasses

1.109.6. Bioactive Glass Ceramics

1.109.7. Calcium Phosphate Ceramics

1.109.8. Silica-Calcium Phosphate Nanocomposite

1.109.9. Silica-Xerogel

1.109.10. Conclusion

1.110. Bioactive Glass-Ceramics


1.110.1. AW Glass-Ceramic

1.110.2. Apatite–Mica Glass-Ceramics

1.110.3. Apatite–Mullite Glass-Ceramics

1.112. Calcium Phosphate Coatings

1.112.1. Introduction

1.112.2. Calcium Phosphates

1.112.3. Titanium Implants

1.112.4. Plasma Spraying of CaP Coatings

1.112.5. Electrochemical Deposition of CaP Coatings

1.112.6. Biomimetic CaP Coatings

1.112.7. Conclusion and Perspectives

1.113. Bioactive Layer Formation on Metals and Polymers


1.113.1. Introduction

1.113.2. Bioactive Layers

1.113.3. Future Perspectives

1.113.4. Additional Reading

1.114. Bioactivity: Mechanisms



1.114.1. Introduction

1.114.2. Mechanisms of Bioactive Behavior

1.114.3. Mechanisms of Biodegradation of Bioactive Ceramics

1.114.4. Summary

1.115. Calcium Phosphates for Cell Transfection


1.115.1. Introduction

1.115.2. Applications of Bioceramic Cell Transfection

1.115.3. The Role of Bioceramic Characteristics for their Applications

1.115.4. Traditional Use of Calcium Phosphate for Cell Transfection

1.115.5. Hydroxylapatite Ceramics for Cell Transfection

1.115.6. Perspectives and Material Evolution

1.116. Bioactive Ceramics: Cements


1.116.1. Introduction

1.116.2. Calcium Sulfate

1.116.3. Portland Cement and MTA

1.116.4. Apatite Cement

1.116.5. Brushite Cement

1.116.6. Future Direction

1.117. Phosphate-Based Glasses


1.117.1. Phosphate Glasses: Physical Properties and Processing

1.117.2. Biological Properties of Phosphate Glasses

1.117.3. Therapeutic Actions of Phosphate Glasses

1.118. Calcium Phosphate Ceramics with Inorganic Additives


1.118.1. Introduction

1.118.2. Bone

1.118.3. Current Methods in Bone Regeneration

1.118.4. Improvement of Synthetic Bone Graft Substitutes

1.118.5. Trace Elements in Bone Metabolism and Processes Related to Bone Formation

1.118.6. Inorganic Additives in Calcium Phosphate Ceramics

1.118.7. Future Perspectives

1.119. Silicon-Containing Apatites


1.119.1. Introduction

1.119.2. Synthesis and Characterization of Silicon-Containing Apatites

1.119.3. In Vitro and In Vivo Studies

1.119.4. Mechanisms of Enhanced Biological Response

1.119.5. Other Silicon-Containing Calcium Phosphate Ceramics

1.119.6. Conclusions and Future Directions

1.120. Synthetic Bone Grafts: Clinical Use


1.120.1. Introduction

1.120.2. A Brief History of Bone Grafts

1.120.3. Synthetic Bone Graft Substitutes

1.120.4. Conclusion

1.121. Polymer Fundamentals: Polymer Synthesis

1.121.1. Introduction to Polymer Science

1.121.2. Polycondensation

1.121.3. Addition Polymerization

1.121.4. Polymer Reactions

1.121.5. Conclusion

1.122. Structural Biomedical Polymers (Nondegradable)

1.122.1. Historical Overview

1.122.2. Classifications of Medical Polymers and Their Applications

1.122.3. Designing Structural Implants with Polymers

1.122.4. Summary

1.123. Degradable Polymers


1.123.1. Introduction

1.123.2. Overview of PLGA Copolymers

1.123.3. Parameters Affecting Degradation Rate of PLGA

1.123.4. Biocompatibility of PLGA

1.123.5. Applications of PLGA Across Length Scales

1.123.6. Rationale for Development of PPEs

1.123.7. Structure–Function Relationships of PPEs

1.123.8. Toxicity and Biocompatibility of PPEs

1.123.9. Design of PPE Drug Carriers

1.123.10. Design of Thermoresponsive PPEs

1.123.11. Design of PPE and PPA Gene Carriers

1.123.12. Conclusion

1.124. Polymer Films Using LbL Self-Assembly


1.124.1. Introduction: Strategies for Surface Modification with Polymers

1.124.2. Fundamentals of Multilayer Formation: LbL Thin Films

1.124.3. Conclusions

1.126. Shape-Memory Polymers


1.126.1. Fundamental Principles of Shape-Memory Polymers and of the Quantification of Shape-Memory Properties

1.126.2. Synthesis and Properties of Selected Examples of SMP Intended for Biomedical Applications

1.126.3. Multifunctional SMPs by Integrating Hydrolytic Degradability or Controlled Drug Release Capability

1.126.4. Biomedical Applications of SMPs

1.127. Electrospinning and Polymer Nanofibers: Process Fundamentals


1.127.1. Introduction

1.127.2. Process Description

1.127.3. Mechanics: Electrostatics and Hydrodynamics

1.127.4. Products of Electrospinning

1.127.5. Summary and Conclusion

1.128. Fluorinated Biomaterials



1.128.1. Introduction

1.128.2. Fluorinated Polymer Chemical and Physical Properties

1.128.3. Fluoropolymers

1.128.4. Biomedical Applications of Fluorinated Biomaterials

1.128.5. Conclusion and Perspectives

1.129. Engineering the Biophysical Properties of Basement Membranes into Biomaterials: Fabrication and Effects on Cell Behavior



1.129.1. Introduction

1.129.2. Basement Membrane

1.129.3. Nanostructure Fabrication

1.129.4. Cellular Response to Topographic Cues with Dimensions from Nano- to Micron-Scales

1.130. Electroactive Polymeric Biomaterials



1.130.1. Introduction

1.130.2. Conjugated Polymer Electrode Coatings

1.130.3. Conjugated Polymers on Devices

1.130.4. Implantable Modification of Conjugated Polymers

1.130.5. Conjugated Polymer-Based Drug Delivery

1.130.6. Synthesis of Conducting Polymers In Vivo

1.130.7. Summary and Future Outlook

1.131. Superporous Hydrogels for Drug Delivery Systems


1.131.1. Introduction

1.131.2. Hydrogels in Drug Delivery

1.131.3. Superporous Hydrogels

1.131.4. SPH Synthesis

1.131.5. SPH Properties

1.131.6. SPH Generations

1.131.7. SPH Scale Up

1.131.8. SPH Stability

1.131.9. SPH Safety

1.131.10. SPH Platform Design for Drug Delivery

1.131.11. SPH in Drug Delivery and Other Areas

1.131.12. Conclusions

1.132. Dynamic Hydrogels


1.132.1. Introduction

1.132.2. Functional Modes/General Dynamic Mechanisms

1.132.3. Specific Stimuli and Response Mechanisms

1.132.4. Biomedical Applications

1.132.5. Future Directions

2.201. Bio-inspired Silica Nanomaterials for Biomedical Applications



2.201.1. Introduction

2.201.2. Biosilicification

2.201.3. Bio-inspired Silica Synthesis for Biomedical Applications

2.201.4. Perspectives and Challenges

2.201.5. Conclusion

2.202. Engineering Viruses For Gene Therapy


2.202.1. Introduction

2.202.2. Viral Engineering

2.202.3. Design of Artificial Viruses

2.202.4. Conclusions and Future Work

2.203. Protein-Engineered Biomaterials: Synthesis and Characterization


2.203.1. Introduction

2.203.2. Rational Design and Modular Building Blocks

2.203.3. Synthesis and Purification

2.203.4. Postsynthesis Materials Processing

2.203.5. Characterization

2.203.6. Biological Interactions and Immunogenicity

2.203.7. Future Directions and Conclusions

2.204. Peptoids: Synthesis, Characterization, and Nanostructures


2.204.1. Introduction

2.204.2. Synthesis

2.204.3. Peptoid Structure and Characterization

2.204.4. Combinatorial Discovery of Peptoid Ligands

2.204.5. Drug Discovery

2.204.6. Cellular Delivery/Uptake Vectors

2.204.7. Biomimetic Materials

2.204.8. Summary and Future Directions

2.205. Self-Assembling Biomaterials


2.205.1. Introduction

2.205.2. Planar Self-Assembling Systems

2.205.3. 3D Self-Assembling Systems

2.205.4. Modulating the Mechanics of Self-Assembling Systems

2.205.5. Advantages Provided by Self-Assembled Systems for Biomaterials Applications

2.205.6. Immune and Inflammatory Responses to Self-Assembling Materials

2.205.7. In vivo Applications of Self-Assembled Biomaterials

2.205.8. Concluding Remarks

2.206. Phages as Tools for Functional Nanomaterials Development


2.206.1. Introduction

2.206.2. Phages for Inorganic–Organic Hybrid Materials

2.206.3. Phage for Energy Materials

2.206.4. Phage for Sensing Materials

2.206.5. Phage for Biomedical Application

2.206.6. Summary and Future Perspectives

2.207. Extracellular Matrix: Inspired Biomaterials


2.207.1. Introduction

2.207.2. Overview of ECM Structure and Function

2.207.3. Types of ECM Mimicry

2.207.4. Future Directions

2.208. Artificial Extracellular Matrices to Functionalize Biomaterial Surfaces


2.208.1. Introduction

2.208.2. Components to Be Used for aECM

2.208.3. Biological Interaction Profiles of aECM and Their Components

2.208.4. Preparation and Structure of aECM

2.208.5. Biochemical Characterization of aECM

2.208.6. Immobilization of aECM

2.208.7. Cell Biological Effects of aECM

2.208.8. Results from Animal Experiments

2.208.9. Conclusions and Outlook

2.209. Materials as Artificial Stem Cell Microenvironments


2.209.1. Introduction

2.209.2. The Adult Stem Cell and Its Niche

2.209.3. Naturally Derived ECM Components for In Vitro Stem Cell Manipulation

2.209.4. Engineered Substrates as Artificial Stem Cell Niches

2.209.5. Topographically Patterned Substrates as Versatile Stem Cell Microenvironments

2.209.6. Biomaterials Approaches to Emulate Stem Cell Niches in 3D

2.209.7. Conclusions

2.210. Bone as a Material


2.210.1. Introduction

2.210.2. Bone Composition

2.210.3. Bone Formation

2.210.4. Bone Structure and Hierarchical Organization

2.210.5. Bone Mechanical Behavior

2.210.6. Bone as a Dynamic Adaptive Material

2.210.7. Bone as a Material During Disease and Drug Treatment

2.210.8. Conclusion

2.211. Polymers of Biological Origin


2.211.1. Introduction

2.211.2. Natural-Based Polymeric Systems

2.211.3. Processing of TE Scaffolds

2.211.4. Cell Encapsulation in Injectable Biodegradable Hydrogels for TE Applications

2.211.5. Final Remarks

2.212. Silk Biomaterials


2.212.1. Overview

2.212.2. Silk Film Biomaterials

2.212.3. Silk Sponge Scaffold Biomaterials

2.212.4. Silk Nanofiber Biomaterials

2.212.5. Silk Hydrogel Biomaterials

2.212.6. Silk Microsphere and Nanoparticle Biomaterials

2.212.7. Silk Optical Biomaterials

2.212.8. Other Silk Materials

2.212.9. Conclusions

2.213. Chitosan


2.213.1. Sources, Analysis, and Properties

2.213.2. Processing

2.213.3. Biomedical Applications

2.213.4. Future Prospects

2.214. Hyaluronic Acid



2.214.1. Introduction

2.214.2. Production of HA

2.214.3. Analysis and Industry Standards

2.214.4. Chemical Modification of HA

2.214.5. Medical Applications of HA

2.214.6. Future Perspectives and Conclusions

2.215. Collagen: Materials Analysis and Implant Uses



2.215.1. Origins of Collagen and Role in Animal Physiology

2.215.2. The Biochemical Fingerprint of Collagen

2.215.3. Sources of Collagen

2.215.4. Collagen: Purification and Analysis

2.215.5. Biomedical Applications of Collagen

2.215.6. Outlook and Future for Collagen Materials

2.216. Collagen–GAG Materials


2.216.1. Introduction

2.216.2. Fabrication of Collagen–GAG Materials

2.216.3. Characterization of Collagen–GAG Materials

2.216.4. In Vitro Applications

2.216.5. In Vivo Applications

2.216.6. Conclusions

2.217. Fibrin


2.217.1. Historical Perspective

2.217.2. Composition, Structure, and Properties

2.217.3. Fibrin Use as a Delivery System

2.217.4. Fibrin in Tissue Engineering Applications

2.217.5. Fibrin in Clinical Practice

2.217.6. Conclusion

2.218. Elastin Biopolymers


2.218.1. Recombinant Human Tropoelastin-Based Constructs

2.218.2. The Elastin-Like Recombinamers

2.218.3. Animal-Derived Solubilized Elastin

2.219. Biophysical Analysis of Amyloid Formation



2.219.1. Introduction

2.219.2. Monomer Folding

2.219.3. Aggregation Intermediates

2.219.4. Mature Amyloid Fibrils

2.219.5. Conclusion

2.220. Extracellular Matrix as Biomimetic Biomaterial: Biological Matrices for Tissue Regeneration


2.220.1. Extracellular Matrix

2.220.2. Materials Applied in TE

2.220.3. Induction of Graft Vascularization

2.220.4. Biological Vascularized Scaffold

2.220.5. Summary and Future Directions

2.221. Decellularized Scaffolds


2.221.1. Introduction

2.221.2. Decellularization Methodology

2.221.3. Origin of Decellularized Scaffolds and their Applications

2.221.4. Concluding Remarks

2.223. Bacterial Cellulose as Biomaterial


2.223.1. Introduction

2.223.2. Bacterial Cellulose: Growth

2.223.3. Modification of Nanostructure

2.223.4. Engineering of Morphology

2.223.5. Shaping in 3D Structure

2.223.6. Biocompatibility

2.223.7. Biomechanics

2.223.8. Cell Interactions and Migration

2.223.9. Biomedical Applications

2.223.10. Future Outlook

3.301. Surface Analysis and Biointerfaces: Vacuum and Ambient In Situ Techniques



3.301.1. Introduction

3.301.2. Ambient Analytical Methods

3.301.3. Ultrahigh Vacuum Surface Analytical Techniques

3.301.4. Next Challenges: Nanomaterial Surfaces

3.301.5. Conclusions

3.302. Atomic Force Microscopy


3.302.1. Introduction

3.302.2. Fundamentals of the AFM

3.302.3. Force–Distance Measurement and Force Mapping

3.302.4. Nanoindentation and Measurement of Near-Surface Nanomechanical Properties of Polymeric Biomaterials

3.302.5. Probing Molecular Interaction and Recognition Sites on Biosurfaces

3.302.6. Limitations and Perspectives

3.303. Proteomic and Advanced Biochemical Techniques to Study Protein Adsorption


3.303.1. Introduction

3.303.2. Unbiased Analysis of Adsorbed Proteins by Polyacrylamide Gel Electrophoresis

3.303.3. Analysis of Adsorbed Proteins by 2DPAGE

3.303.4. Quantification of Protein Amounts by Mass Spectrometry

3.303.5. Proteomics to Study Protein Denaturation on Surfaces

3.303.6. Challenges of the Proteomics Approach

3.303.7. Conclusions

3.304. Developments in High-Resolution CT: Studying Bioregeneration by Hard X-ray Synchrotron-Based Microtomography



3.304.1. Hard X-ray Microimaging

3.304.2. Comparative Animal Study of Bioceramic-Supported Bone Regeneration

3.304.3. Bone Regeneration After Sinus Floor Augmentation in Humans

3.304.4. Summary

3.305. Biomedical Thin Films: Mechanical Properties



3.305.1. Introduction

3.305.2. Coating Techniques

3.305.3. Thin Film Mechanical Testing: Methods

3.305.4. Concluding Remarks

3.306. Microindentation


3.306.1. Introduction

3.306.2. Overview of Nanoindentation Technique

3.306.3. Application of Nanoindentation to Biomaterials

3.306.4. Summary

3.307. Finite Element Analysis in Bone Research: A Computational Method Relating Structure to Mechanical Function


3.307.1. Introduction

3.307.2. Macroscale: Whole Bone

3.307.3. Mesoscale: Trabecular Bone

3.307.4. Microscale: Ultrastructural Features

3.307.5. Nanoscale: Mineral and Collagen

3.307.6. Conclusions and Future Directions

3.308. The Mechanics of Native and Engineered Cardiac Soft Tissues



3.308.1. Introduction

3.308.2. Heart Valve Tissues

3.308.3. Myocardium

3.308.4. Constitutive Models of Soft Tissues

3.308.5. Emulating Native Tissue Mechanical Behavior in Engineered Tissues

3.309. Fluid Mechanics: Transport and Diffusion Analyses as Applied in Biomaterials Studies


3.309.1. Introduction

3.309.2. Transport Phenomena: Diffusive, Convective, and Reactive Transport Mechanisms

3.309.3. Analysis of Transport Models in Porous Media

3.309.4. Conclusion

3.310. Computational Methods Related to Reaction Chemistry



3.310.1. Introduction

3.310.2. Computational Methods

3.310.3. Applications

3.311. Molecular Simulation Methods to Investigate Protein Adsorption Behavior at the Atomic Level



3.311.1. Introduction

3.311.2. Fundamental Aspects of Protein Adsorption Behavior

3.311.3. Molecular Simulation Methods and Their Relevance to Protein Adsorption

3.311.4. Application of All-Atom Modeling Methods to Simulate Protein–Surface Interactions

3.311.5. Current Limitations and Directions for Further Development

3.311.6. Concluding Remarks

3.312. Cell Culture Systems for Studying Biomaterial Interactions with Biological Barriers



3.312.1. Introduction

3.312.2. The Upper Respiratory Tract: Barrier Functions of the Bronchial Epithelium

3.312.3. The Lower Respiratory Tract: Cell Culture Models Mimicking the Biological Barriers of the Distal Lung

3.312.4. In Vitro Studies with Endothelial Cells from the BBB

3.312.5. Conclusion and Future Perspectives

3.313. Histological Analysis


3.313.1. Introduction

3.313.2. Preservation of Tissue

3.313.3. Undecalcified Versus Decalcified

3.313.4. Embedding Techniques

3.313.5. Sectioning Techniques

3.313.6. Staining Methods

3.313.7. Quantification Methods

3.313.8. Summary and Future Directions

3.314. Materials to Control and Measure Cell Function


3.314.1. Introduction

3.314.2. Influence of Surface Features on Cell Function

3.314.3. Influence of Surface Features on Bacteria Function

3.314.4. Applications in BioMEMs/Microsystems Fields

3.314.5. Conclusions

3.315. Biological Microelectromechanical Systems (BioMEMS) Devices



3.315.1. Introduction

3.315.2. Cell Adhesions to the Microenvironment

3.315.3. BioMEMS Devices to Measure Traction Forces

3.315.4. BioMEMS Devices to Apply Forces to Cells

3.315.5. Microfluidic Systems

3.315.6. Future Directions

3.316. Immunohistochemistry


3.316.1. Introduction to Immunohistochemistry

3.316.2. Factors Contributing to Antibody–Antigen Interaction

3.316.3. Visualization of Antibody by Enzymatic or Fluorescent Labeling and The Advantages and Disadvantages

3.316.4. Basic Immunohistochemistry Protocols and Their Advantages and Disadvantages for Biomaterial Science

3.316.5. Detection of Pathobiological Processes and Associated Cellular Events in an Implanted Site

3.316.6. Implant Evaluation Using Immunohistochemical Methods

3.317. Fluorescence Imaging of Cell–Biomaterial Interactions



3.317.1. Introduction

3.317.2. Principles, Instrumentation, and Methodology for Cell Imaging

3.317.3. Probing Cell–Biomaterial Interactions

3.317.4. Looking to the Future

3.318. Molecular Imaging


3.318.1. Introduction

3.318.2. Nanomaterials

3.318.3. Nanovesicles

3.318.4. Polymeric Assemblies

3.318.5. Future Outlook

3.319. Characterization of Nanoparticles in Biological Environments



3.319.1. Introduction

3.319.2. Interactions of Nanoparticles

3.319.3. Characterization of Nanoparticles in or from Solution

3.319.4. Examples of Nanoparticles in Biological Environments

3.319.5. Conclusions and Outlook

3.320. Nanostructured Polymeric Films for Cell Biology


3.320.1. Introduction

3.320.2. Controlled Protein Adsorption on BCP and Polymer Blend Surfaces

3.320.3. Protein and Cell Binding via Affinity Interactions Templated by Polymer Surfaces

3.320.4. Coassembly of BCPS with Peptides and Proteins in Thin Films

3.320.5. BCP Surfaces for Biocompatibility and Antifouling Applications

3.320.6. BCP Micelle Surfaces for Controlled Release Applications

3.320.7. Conclusion

3.321. Microarrays in Biomaterials Research


3.321.1. Introduction

3.321.2. Principle of Microarray

3.321.3. Application of Microarray

3.321.4. Future Prospects of Microarray

3.322. Infrared and Raman Microscopy and Imaging of Biomaterials


3.322.1. Introduction

3.322.2. Instrumentation, Sampling, and Data Processing

3.322.3. Applications to Biomaterials

3.322.4. Conclusions

3.323. Magnetic Resonance of Bone Microstructure and Chemistry


3.323.1. Introduction

3.323.2. Fundamentals of Magnetic Resonance

3.323.3. Quantitative MRI of Trabecular and Cortical Bone Microstructure

3.323.4. Bone Water and Porosity

3.323.5. NMR Spectroscopy and MRI of Bone Matrix and Mineral

3.323.6. Summary and Conclusions

3.324. Fluorescent Nanoparticles for Biological Imaging


3.324.1. Introduction

3.324.2. Fluorescent Nanoparticles: Synthesis and Surface Modification

3.324.3. Fluorescent Nanoparticles: In Vitro Applications

3.324.4. Fluorescent Nanoparticles: In Vivo Applications

3.324.5. Future Perspective

3.325. Imaging Mineralized Tissues in Vertebrates


3.325.1. Introduction

3.325.2. Structure of Mineralized Tissues

3.325.3. Heterogeneity of Mineral Content and the Need for Imaging Techniques

3.325.4. Estimates of Total Bone Mineral Content

3.325.5. Imaging of Mineralized Tissues

3.325.6. Property Mapping in Mineralized Tissues

3.325.7. Conclusions

3.326. Imaging and Diagnosis of Biological Markers


3.326.1. Introduction

3.326.2. Principles of MR and the Implications for Imaging and Diagnosis

3.326.3. Viable Molecules, Nuclei, and Experiments for MR Studies

3.326.4. Case Study: Biological Markers for the Diagnosis of DDD

3.326.5. Case Study: MR for Diagnosing Bone Disease and Treatment

3.326.6. Summary and Future of Imaging and Diagnosis of Biological Markers

3.327. Intracellular Probes


3.327.1. Introduction

3.327.2. Fluorescence-Based Intracellular Probes

3.327.3. Optical-Label-Free Intracellular Probes

3.327.4. Conclusion

3.328. Biosensors Based on Sol–Gel-Derived Materials


3.328.1. Introduction

3.328.2. Sol–Gel Bioencapsulation

3.328.3. Applications of Sol–Gel Biosensors

3.328.4. Conclusions and Future Trends

3.329. Hydrogels in Biosensing Applications

3.329.1. Introduction

3.329.2. Physicochemical Sensing Mechanisms

3.329.3. Biochemical Sensing Mechanisms

3.329.4. Summary

3.330. Carbon Nanotube-Based Sensors: Overview

3.330.1. Introduction

3.330.2. CNTs and Related Carbon-Based Nanostructures

3.330.3. Manufacturing Devices from Carbon Nanostructures

3.330.4. Sensing Applications of Carbon Nanostructures

3.330.5. Future Opportunities

3.331. Conjugated Polymers for Biosensor Devices


3.331.1. Conjugated Polymers (CPs): History and Perspectives

3.331.2. Using CPs for Electrochemical Biosensor Devices

3.331.3. Using CPs for Optical Biosensor Devices

4.401. The Concept of Biocompatibility


4.401.1. Introduction

4.401.2. Wound-Healing Responses Underlying Biocompatibility

4.401.3. Characteristic Features of Tissue Around Implants: Emerging Insights

4.401.4. Summary and Considerations for the Future

4.402. Biocompatibility and the Relationship to Standards: Meaning and Scope of Biomaterials Testing


4.402.1. Introduction

4.402.2. Biocompatibility

4.402.3. Materials for Medical Devices

4.402.4. In Vitro Tests for Biocompatibility

4.402.5. In Vivo Tests for Biocompatibility

4.402.6. Inflammation, Wound Healing, and the Foreign-Body Response

4.402.7. Hemocompatibility

4.402.8. Immune Responses

4.402.9. Summary and Conclusion

4.403. The Innate Response to Biomaterials


4.403.1. Introduction

4.403.2. Biomaterial Changes

4.403.3. Inflammation and Biomaterials

4.403.4. Evasion Innate Immune System Activation

4.403.5. Enhancement of Innate Immune System Activation

4.403.6. Concluding Remarks

4.404. Adaptive Immune Responses to Biomaterials

4.404.1. Introduction

4.404.2. Recognition of Biomaterials by the Adaptive Immune System

4.404.3. Consequences of the Adaptive Response

4.404.4. Approaches to Engineer Adaptive Responses with Biomaterials

4.404.5. Conclusions

4.405. Leukocyte–Biomaterial Interaction In Vitro


4.405.1. Introduction

4.405.2. Characterizing the Inflammatory Response

4.406. Protein Interactions with Biomaterials

4.406.1. Introduction

4.406.2. Surface Wettability, Topography, and Protein Adsorption

4.406.3. Surface-Activated Coagulation

4.406.4. Immune Complement at Biomaterials

4.406.5. Consequences of Protein Adsorption

4.406.6. Summary and Future Directions

4.407. Bacterial Adhesion and Biomaterial Surfaces


4.407.1. Introduction

4.407.2. Laboratory Methods for the Study of Bacterial Adhesion

4.407.3. Bacterial Characterization Methods

4.407.4. Theory and Mechanisms of Bacterial Adhesion

4.407.5. Mechanisms of Bacterial Adhesion

4.407.6. The Influence of Biomaterial Surface Properties on Bacterial Adhesion

4.407.7. Strategies to Reduce Bacterial Adhesion

4.407.8. Summary and Perspectives

4.408. Integrin-Activated Reactions to Metallic Implant Surfaces


4.408.1. Introduction

4.408.2. Integrins

4.408.3. Integrin Function

4.408.4. Integrin-Signaling Pathways

4.408.5. Integrin Binding to Biomaterials

4.408.6. Functionalizing Implant Surfaces Using Adhesion Molecules

4.408.7. Conclusions

4.409. Surfaces and Cell Behavior



4.409.1. Introduction

4.409.2. Manufacturing Surface Topography

4.409.3. History of Differentiated Cell Guidance by Nanostructures

4.409.4. The History of Stem Cells and Nanotopography

4.409.5. Low Adhesion Materials

4.409.6. Nanotopography as a Noninvasive Tool for Cell Biology

4.409.7. Conclusions and Future Perspectives

4.410. Sterilization of Biomaterials of Synthetic and Biological Origin


4.410.1. Introduction

4.410.2. Sterilization Methods

4.410.3. Sterilization of Biomaterials of Synthetic and Biological Origin

4.410.4. Evaluation of Effect of Sterilization on Biomaterials

4.411. Peptide- and Protein-Modified Surfaces

Amino Acid Abbreviations


4.411.1. Introduction

4.411.2. Peptides Versus Proteins

4.411.3. Immobilization Strategies

4.411.4. Functional Parameters

4.411.5. Sample Applications

4.411.6. Conclusions and Outlook

4.412. Rational and Combinatorial Methods to Create Designer Protein Interfaces


4.412.1. Introduction

4.412.2. Rational Engineering

4.412.3. Combinatorial Engineering

4.412.4. Protein Engineering Considerations for Biomaterials: The Interface Between Proteins and Materials

4.412.5. Conclusions and Future Directions

4.413. Patterned Biointerfaces



4.413.1. Introduction

4.413.2. Patterning Techniques

4.413.3. Biointerfacing with Patterned Surfaces

4.414. Molecular Biomimetic Designs for Controlling Surface Interactions



4.414.1. Introduction

4.414.2. Biomaterials' Failure Mechanisms

4.414.3. Approaches for Controlling Surface Biological Interactions

4.414.4. ECM Biomimetics

4.414.5. Summary and Outlook

4.415. Surface Engineering Using Peptide Amphiphiles



4.415.1. Introduction

4.415.2. The Amphiphilic Nature of Life's Events

4.415.3. PAs: Synthesis, Physicochemical Characterization, and Self-Assembly

4.415.4. The Multifunctional (Soft) Nanoparticle Concept

4.415.5. Protein-Like Structures to 3D Hierarchical Nanostructures

4.415.6. Applications in Biomedical Sciences: Tissue and Stem Cell Engineering

4.415.7. Summary and Future Directions

4.417. Tethered Antibiotics



4.417.1. Implant-Associated Infection in Orthopedic Materials

4.417.2. Bacterial Responses to Orthopedic Implants

4.417.3. Antibiotic Prophylaxis and Treatment of Surgical Infection

4.417.4. Surface Tethering of Antibiotics to Prevent Bacterial Adhesion

4.418. Engineering Interfaces for Infection Immunity


4.418.1. The Problem

4.418.2. Innate and Adaptive Immune Responses

4.418.3. Engineering Infection Immunity

4.418.4. Concluding Remarks

4.419. Vaccine and Immunotherapy Delivery



4.419.1. Introduction

4.419.2. The Paradigm of Immune Responses in Infection Versus Vaccination

4.419.3. Biomaterials as Delivery Vehicles for Vaccines and Immunomodulators

4.419.4. Biomaterials as Immunostimulators and Carriers of Immunostimulatory Adjuvants for Vaccines

4.419.5. Future Directions

4.419.6. Conclusions

4.420. Drug Delivery via Heparin Conjugates


4.420.1. Rationale for Using Heparin Conjugates for Drug Delivery

4.420.2. Methods for Heparin Immobilization

4.420.3. Use of Heparin Mimetic Molecules for Delivery of Heparin-Binding Growth Factors

4.420.4. Summary

4.421. Self-Assembled Prodrugs



4.421.1. Introduction

4.421.2. Challenges and Opportunities of Hydrogels in Drug Delivery

4.421.3. Self-Assembled Prodrugs

4.421.4. Self-Assembled Irreversible Prodrug-Based Hydrogels

4.421.5. Conclusions and Outlook

4.422. pH-Responsive Polymers for the Intracellular Delivery of Biomolecular Drugs

4.422.1. Introduction

4.422.2. Acid–Base Equilibria and pH-Responsive Chemistries

4.422.3. Anionic pH-Responsive Polymers

4.422.4. Acid-Degradable Delivery Vehicles

4.422.5. Osmotically Disruptive Cationic Polymers

4.422.6. Histidine- and Imidazole-Containing Copolymers

4.422.7. Fusogenic Peptides

4.422.8. Future Perspectives

4.423. Polymeric Drug Conjugates by Controlled Radical Polymerization



4.423.1. Introduction

4.423.2. Overview of Controlled Radical Polymerization

4.423.3. Examples of Polymer Conjugates Synthesized by Controlled Radical Polymerization

4.423.4. Prospects and Challenges

4.424. Nanoparticles for Nucleic Acid Delivery



4.424.1. Introduction

4.424.2. General Classes of Nucleic Acid Delivery Systems

4.424.3. Classes of Nonviral Vectors

4.424.4. Opportunities and Challenges in NP Therapeutics: Biological Barriers to Nucleic Acid Delivery

4.424.5. Conclusions

4.426. Electrospun Fibers for Drug Delivery


4.426.1. Introduction

4.426.2. Principles of Electrospinning

4.426.3. Drug Delivery from Electrospun Fibers

4.426.4. Conclusions and Future Directions

4.427. Cell-Demanded Release of Growth Factors



4.427.1. Introduction

4.427.2. Enabling Polymer Hydrogels for Cell-Demanded Release

4.427.3. Preclinical Evaluation in Angiogenesis

4.427.4. Conclusion and Future Directions

4.428. Sol–Gel Processed Oxide Controlled Release Materials


4.428.1. Introduction

4.428.2. Sol–Gel Process

4.428.3. Drug Release Mechanisms

4.428.4. Control of Release Kinetics

4.428.5. Biocompatibility and Resorption

4.428.6. Applications

4.428.7. Summary

4.429. Ordered Mesoporous Silica Materials


4.429.1. Introduction

4.429.2. Ordered Mesoporous Materials: General Remarks

4.429.3. Biocompatibility of Mesoporous Materials

4.429.4. Mesoporous Materials for Local Drug Delivery

4.429.5. Bioactivity of Mesoporous Matrices

4.429.6. Hierarchical Macroporous Scaffolds for Bone Tissue Engineering

4.430. Silica-Based Mesoporous Nanospheres


4.430.1. Introduction

4.430.2. Synthesis of Nonporous Silica Nanospheres

4.430.3. Synthesis of MSNs

4.430.4. Physicochemical Properties and Characterization

4.430.5. Unique Biomaterial Considerations

4.430.6. Conclusion

4.431. Encapsulation of Cells (Cellular Delivery) Using Sol–Gel Systems



4.431.1. Introduction

4.431.2. Sol–Gel Silicates

4.431.3. Cell Delivery in Temperature-Sensitive Sol–Gel Systems

4.431.4. Conclusion and Future Directions

4.432. Layered Double Hydroxides as Controlled Release Materials


4.432.1. Introduction

4.432.2. LDHs and Intercalation

4.432.3. Stabilization of Biomolecules via Intercalation

4.432.4. Controlled Release of Intercalated Biomolecules

4.432.5. Enhanced Cellular Uptake

4.432.6. Conclusion and Perspectives

4.433. Porous Metal–Organic Frameworks as New Drug Carriers



4.433.1. Introduction

4.433.2. Adsorption and Delivery of Therapeutic Molecules

4.433.3. Adsorption and Delivery of Biological Gases

4.433.4. Toxicity and Stability Issues

4.433.5. Formulation

4.433.6. Conclusion and Perspectives

4.434. Hybrid Magnetic Nanoparticles for Targeted Delivery

4.434.1. Introduction

4.434.2. Magnetism of MNPs

4.434.3. MF Design and Preparation

4.434.4. Size/Surface Requirements with Regard to i.v. Administration

4.434.5. MNPs as Contrast Agents for MRI

4.434.6. MNPs as Mediators for Magnetic Hyperthermia

4.434.7. MNPs Within Carriers for Drug Delivery

4.434.8. Conclusion

5.501. Scaffolds: Flow Perfusion Bioreactor Design



5.501.1. Introduction

5.501.2. Mass Transport within Scaffolds

5.501.3. Perfusion Bioreactors

5.501.4. Design Parameters of Flow Perfusion Bioreactors

5.501.5. Current Flow Perfusion Bioreactor Designs and Functions

5.501.6. Future Progress

5.501.7. Conclusions

5.502. Engineering Scaffold Mechanical and Mass Transport Properties



5.502.1. Introduction

5.502.2. Hierarchical Computational Scaffold Design

5.502.3. Fabricating Designed Scaffolds

5.502.4. Designed Scaffold Architecture Influences Tissue Regeneration

5.502.5. Conclusion

5.503. Biomaterials and the Microvasculature



5.503.1. Introduction

5.503.2. Biomedical Engineering Applications Dependent on Neovascularization In or Around Biomaterials

5.503.3. Survey of Neovascularization

5.503.4. Properties of Biomaterials Regulating Microvascular Network Formation In, On, and Around Biomaterials

5.503.5. Case Studies

5.504. Effect of Substrate Modulus on Cell Function and Differentiation


5.504.1. Introduction

5.504.2. Young's Modulus

5.504.3. Fabrication of Substrates with Defined Material Modulus

5.504.4. Cell Functions and Differentiation

5.504.5. Conclusion

5.505. Quantifying Integrin–Ligand Engagement and Cell Phenotype in 3D Scaffolds


5.505.1. Introduction

5.505.2. Quantifying Integrin–Ligand Forces

5.505.3. Quantifying Type and Number of Integrin–Ligand Binding

5.505.4. Conclusion

5.506. Effects of Mechanical Stress on Cells


5.506.1. Introduction

5.506.2. Mechanical Environment of the Cell

5.506.3. Subcellular Structures Involved in Mechanotransduction

5.506.4. Molecular Mechanotransduction

5.506.5. Response of Cells to Mechanical Stress and Implications for Tissue Engineering

5.507. Tissue Engineering and Selection of Cells



5.507.1. Why Do Tissue Engineering Approaches Need a Cell Source?

5.507.2. Cell Sources Used in Tissue Engineering Strategies

5.507.3. Patient Delivery Challenges: Controlling Cells in the Body

5.507.4. Donor Versus Host Immune Issues

5.507.5. Donor Versus Host: Cell/Tissue Integration

5.507.6. Safety and Stability

5.507.7. Conclusion

5.508. Scaffold Materials for hES Cell Culture and Differentiation


5.508.1. Introduction

5.508.2. Biomaterials for Undifferentiated hESC Culture

5.508.3. Biomaterials for hESC Differentiation

5.508.4. Conclusions and Future Work

5.508.5. Summary

5.509. Cell Encapsulation


5.509.1. Introduction

5.509.2. Methods

5.509.3. Process

5.509.4. Representative Applications

5.509.5. Summary

5.510. Engineered Bioactive Molecules



5.510.1. Introduction

5.510.2. Proteins

5.510.3. Nucleic Acids

5.510.4. Lipids and Liposomes

5.511. Rotating-Wall Vessels for Cell Culture


5.511.1. Introduction

5.511.2. Operating Principles of RWV

5.511.3. Scaffolds and Microcarriers for Cell Culture in RWV

5.511.4. Cell Culture in RWV

5.511.5. Other Applications of RWV

5.512. In Vivo Bioreactors


5.512.1. Introduction

5.512.2. Elements of the In Vivo Bioreactor

5.512.3. Applications and Tissues

5.513. Systems Biology in Biomaterials and Tissue Engineering


5.513.1. Introduction

5.513.2. Discrete Component-Centered Approach

5.513.3. High-Throughput Component-Centered Approach

5.513.4. Process-Centered Systems Approach

5.513.5. Future Outlook

5.514. Chondrocyte Transplantation and Selection


5.514.1. Introduction

5.514.2. Cell Therapy and Cartilage Regeneration: State of the Art

5.514.3. Cell Therapy Concepts in Cartilage Disease and Osteoarthritis

5.514.4. Molecular Control Mechanisms in the Knee Joint – Implications for Cartilage Repair and OA

5.514.5. The Uniqueness of Hyaline Cartilage Chondrocytes

5.514.6. Adult Stem Cells and Stem Cell Niches

5.514.7. Improvements in ACT Cell Technology – Alternative Cell Sources

5.514.8. Autologous Use of Cells

5.514.9. Universal Donor Cell Lines for Cartilage Repair

5.514.10. Conclusion

5.515. Cartilage Tissue Engineering


5.515.1. Introduction

5.515.2. Articular Cartilage Maturation and Synovial Fluid Formation

5.515.3. Mechanical Properties and Models of Articular Cartilage and Synovial Fluid

5.515.4. Mechanical Effects on Cartilage Maturation and Synovial Fluid Pathology

5.515.5. Engineering Cartilaginous Tissue and Synovial Fluid

5.516. Biomaterials in Cartilage Tissue Engineering


5.516.1. Introduction

5.516.2. Cell Sources

5.516.3. Scaffolds

5.516.4. Growth Factors

5.516.5. Clinical Repair Techniques

5.516.6. Conclusion

5.517. Tissue Engineering of the Temporomandibular Joint


5.517.1. Introduction

5.517.2. Gross Anatomy and Physiology of the TMJ

5.517.3. Characterization of TMJ Tissues

5.517.4. Pathology of the TMJ

5.517.5. Current Therapies

5.517.6. Tissue Engineering

5.517.7. Future Directions for TMJ Tissue Engineering

5.517.8. Conclusions

5.518. Endocultivation: Computer Designed, Autologous, Vascularized Bone Grafts

5.518.1. Introduction

5.518.2. Endocultivation of Autologous Vascularized Bone Grafts

5.518.3. Clinical Applications of Endocultivation: Tissue Engineering of Autologous Customized Vascularized Bone Replacements In Vivo

5.518.4. Clinical Results

5.518.5. Future Improvements

5.518.6. Summary

5.519. Biomaterials Selection for Dental Pulp Regeneration


5.519.1. Introduction

5.519.2. Biomaterial Selections

5.519.3. In Vivo Dental Pulp Regeneration: State of the Art

5.519.4. Conclusions

5.520. Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds


5.520.1. Introduction

5.520.2. Scaffold Requirements

5.520.3. Fundamentals of Ceramic Bioactivity

5.520.4. Characteristics of Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds for Bone Tissue-Engineering Scaffold

5.520.5. Modifications of Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds

5.520.6. Conclusion and Future Directions

5.521. Calcium Phosphates and Bone Induction


5.521.1. Bone and Its Biology

5.521.2. Bone Grafting and the Strategies

5.521.3. Biomaterials for Bone Substitution

5.521.4. Bone Induction Associated with Materials

5.521.5. Role of Calcium Phosphate in Bone Induction

5.521.6. Material Factors

5.521.7. Mechanism of Bone Induction

5.521.8. Clinical Significance of Osteoinductive Materials

5.521.9. Future Directions

5.522. Bone Tissue Engineering: Growth Factors and Cytokines


5.522.1. Bone Biology

5.522.2. Growth Factors, Cytokines, Nomenclature, Mechanism of Action

5.522.3. Bone Tissue Engineering: Growth Factors and Cytokines

5.522.4. Cytokines and Bone

5.522.5. Translational Applications of Growth Factors and Cytokines in Bone Tissue Engineering

5.523. Carbon Nanotubes: Applications for In Situ Implant Sensors



5.523.1. Introduction

5.523.2. Making Orthopedic Implant Sensors

5.523.3. Biological Responses to Orthopedic Implant Sensors

5.523.4. Sensing Ability of Orthopedic Implant Sensors

5.523.5. Discussion

5.523.6. Conclusions

5.524. Biomaterials for Replacement and Repair of the Meniscus and Annulus Fibrosus



5.524.1. Overview

5.524.2. Introduction

5.524.3. Structure and Function of the Knee Meniscus

5.524.4. Structure and Function of the AF

5.524.5. Current Clinical Treatments for Damage to or Degeneration of the Meniscus and AF

5.524.6. Current Products for Meniscus and AF Repair and Replacement

5.524.7. Emerging Products for Meniscus and AF Repair and Replacement: Tissue Engineering

5.524.8. Engineering Fiber-Reinforced Tissues with Nanofibrous Scaffolds

5.524.9. Preclinical Models and Evaluation Tools for Engineered AF and Meniscus Products

5.524.10. Conclusions and Future Directions

5.525. Tissue Engineering Approaches to Regeneration of Anterior Cruciate Ligament



5.525.1. Introduction

5.525.2. Biomaterials for Ligament Tissue Engineering

5.525.3. Scaffold Design

5.525.4. Cell Source

5.525.5. Bioreactor System

5.525.6. Local Delivery of Growth Factors

5.525.7. Animal Models for ACL Regeneration

5.525.8. Ligament–Bone Interface

5.525.9. Summary

5.526. Tissue Engineering of Muscle Tissue

5.526.1. Introduction

5.526.2. Importance of Skeletal Muscle Tissue Engineering

5.526.3. Muscle Development and Repair

5.526.4. Scaffolding Materials

5.526.5. Additions to Current Matrices

5.526.6. Vascularization

5.526.7. Innervation

5.526.8. Alternative Cell Types for Skeletal Muscle Engineering

5.526.9. Electrical and Mechanical Stimulation of Skeletal Muscle

5.526.10. Matrix Metalloproteinases

5.526.11. Immune Response to Engineered Muscle

5.526.12. The Aged Niche

5.526.13. Pathological Environment

5.526.14. Future Directions

5.527. Cardiovascular Tissue Engineering


5.527.1. Introduction

5.527.2. Cardiac Patches

5.527.3. Cell Delivery Using Biomaterials

5.527.4. Tissue Engineering of Artificial Vesseles

5.527.5. Tissue Engineering of Heart Valves

5.528. Tissue Engineering of Heart Valves

5.528.1. The Ideal Valvular Substitute

5.528.2. Strategies in Autologous Heart Valve Tissue Engineering

5.528.3. In Vitro Heart Valve Tissue Engineering

5.528.4. In Vivo Heart Valve Tissue Engineering

5.528.5. Cell Sources for Heart Valve Tissue Engineering

5.528.6. Toward Clinical Application – Outlook for the Future

5.529. Biomaterials for Cardiac Cell Transplantation


5.529.1. Introduction

5.529.2. Biomaterial Design Requirements for Cardiac Cell Transplantation

5.529.3. Current Materials

5.529.4. Concluding Remarks

5.530. Medical Applications of Cell Sheet Engineering



5.530.1. Introduction

5.530.2. Functional Tissue Engineering with Cell Sheets

5.530.3. Clinical Application of Cell Sheet Tissue Engineering

5.530.4. Conclusions

5.531. Peripheral Nerve Regeneration


5.531.1. Introduction

5.531.2. Current Approaches to Bridging Nerve Gaps

5.531.3. Concluding Statements

5.532. Nerve Tissue Engineering


5.532.1. Introduction

5.532.2. State of the Art of PNS Tissue Engineering

5.532.3. State of the Art of CNS Tissue Engineering (see Chapter 5.533, Biomaterials for Central Nervous System Regeneration and Chapter 6.630, Biomaterials for Spinal Cord Repair)

5.532.4. Concluding Remarks

5.533. Biomaterials for Central Nervous System Regeneration

5.533.1. Introduction

5.533.2. Biomaterial Therapy Options

5.533.3. Spinal Cord Injury

5.533.4. Alzheimer's Disease

5.533.5. Parkinson's

5.533.6. Biomaterials Used with Stem Cell Therapy

5.533.7. Summary of Biomaterial Therapies in CNS Injury/Disease

5.535. Cartilage Regeneration in Reconstructive Surgery


5.535.1. Introduction

5.535.2. Role of Tissue Engineering

5.535.3. Cell Sources and Materials

5.535.4. Characterization of Scaffolds In Vitro and In Vivo

5.535.5. Conclusions

5.536. Tissue-Engineering Hollow Noncardiac Intrathoracic Organs: State-of-the-Art 2010


5.536.1. Introduction

5.536.2. Historical Background

5.536.3. Tissue-Engineered Trachea: Basic Sciences to Clinical Application and Transplantation

5.536.4. Tissue-Engineered Larynx for Total Laryngeal Replacement and Transplantation: The Ultimate Goal

5.536.5. Future Challenges and Goals

5.536.6. Conclusions

5.537. Adipose Tissue Engineering


5.537.1. Introduction

5.537.2. Adipose Tissue Engineering

5.537.3. Adipose Tissue Structure and Function

5.537.4. Biomaterials for Adipose Tissue Engineering

5.537.5. Future Outlook

5.538. Finger


5.538.1. Introduction

5.538.2. Periosteum for Human Phalanx Model

5.538.3. In Vivo Model for Phalanx

5.538.4. Development of the Human Phalanx Model

5.538.5. Assessment of the Human Phalanx Model

5.538.6. Conclusion and Future Directions

5.539. From Tissue to Organ Engineering



5.539.1. Introduction

5.539.2. Biomaterials

5.539.3. Cells for Use in Tissue Engineering

5.539.4. Cell Therapy with Injectable Substances

5.539.5. Tissue Engineering of Specific Structures

5.539.6. Summary and Conclusion

5.540. Kidney Tissue Engineering


5.540.1. Introduction

5.540.2. Developmental Techniques

5.540.3. Renal Progenitor Cells

5.540.4. Cellular-Based Therapies

5.540.5. Stem Cells for Use in Renal Tissue Regeneration

5.540.6. In Situ Kidney Development

5.540.7. Renal Tubular Assist Devices

5.540.8. Summary and Conclusions

5.541. Liver Tissue Engineering


5.541.1. Introduction

5.541.2. Extracorporeal Liver Support Devices

5.541.3. Implantable Hepatic Support Systems

5.541.4. Conclusions and Future Directions

5.542. Organ Printing


5.542.1. Introduction

5.542.2. 2D Patterning and Cell Printing

5.542.3. 3D Organ-Printing Processes

5.542.4. Future Directions

5.542.5. Conclusions

6.601. Current and Projected Utilization of Total Joint Replacements


6.601.1. Introduction

6.601.2. International Total Hip and Knee Implant Registries

6.601.3. Public Data Sources for Orthopedic Implant Utilization in the United States

6.601.4. Current Utilization of Total Joint Replacements

6.601.5. Projected Utilization of Total Joint Replacements

6.601.6. Summary

6.602. Bone Cement


6.602.1. Introduction

6.602.2. Bone Cement Chemistry

6.602.3. Bone Cement Applications

6.602.4. Mechanical Properties of PMMA–Bone Cement

6.602.5. Improving PMMA–Bone Cement

6.602.6. Summary and Concluding Remarks

6.603. Ultrahigh Molecular Weight Polyethylene Total Joint Implants*


6.603.1. Introduction

6.603.2. General Properties and Processing of UHMWPE

6.603.3. The Effects of Sterilization and Early Developments

6.603.4. Cross-linking Technologies

6.603.5. Vitamin E-Stabilized, Radiation Cross-linked UHMWPE

6.603.6. Other UHMWPEs with Clinical Potential

6.603.7. Conclusions and Future Directions

6.604. Ceramic Prostheses: Clinical Results Worldwide


6.604.1. Introduction

6.604.2. History

6.604.3. Early Clinical Results

6.604.4. Evolution of the Mechanical Properties of Alumina and the New Alumina Matrix Composite

6.604.5. Proven Long-Term Clinical Stability

6.604.6. Biocompatibility

6.604.7. Current Manufacturing State of the Art

6.604.8. Ceramic Component Failure

6.604.9. Recent Clinical Reports of the Use of the Latest Generation of Alumina Ceramics

6.604.10. Statistical Observations of the Largest Ceramic Manufacturer Clinical Report Database (January 2000 to September 2009)

6.604.11. Ceramic Component Squeaking

6.604.12. The Beneficial Wear Properties of Alumina Ceramics Outweigh the Risk of Fracture

6.604.13. Clinical Use of Ceramics in the Global Community

6.604.14. Ceramics Allow Large Diameter Wear Couple with Little Wear Debris

6.604.15. Conclusions

6.605. Porous Coatings in Orthopedics


6.605.1. Introduction

6.605.2. Materials Used for Porous Coatings

6.605.3. Properties of Porous-Coated Implants

6.605.4. Design and Characterization of Porous Materials

6.605.5. Porous Coatings in Tissue Engineering

6.605.6. Summary and Future Directions

6.606. Biological Effects of Wear Debris from Joint Arthroplasties



6.606.1. Introduction

6.606.2. Orthopedic Wear Debris

6.606.3. Biologic Reactions of the Host to Wear Debris

6.606.4. Other Factors Modulating the Biological Activity of Wear Particles

6.606.5. New In Vivo Models and Development of Particle-Induced Osteolysis

6.606.6. Therapeutic Strategies

6.606.7. Conclusion

6.607. Fretting Corrosion of Orthopedic Implants


6.607.1. Introduction

6.607.2. Experimental Methods: Implant Fretting Corrosion

6.607.3. Implant Fretting and Biocompatibility

6.607.4. Conclusions

6.608. Implant Debris: Clinical Data and Relevance


6.608.1. Introduction

6.608.2. Implant Debris Types: Particles and Ions

6.608.3. Local Tissue Effects of Wear and Corrosion

6.608.4. Systemic Effects of Wear and Corrosion

6.608.5. Conclusions

6.609. Orthopedic Implant Use and Infection


6.609.1. Orthopedic Implants

6.609.2. Periprosthetic Infection

6.609.3. The Diagnostic Dilemmas

6.609.4. An Interjection on Orthopedic Trauma

6.609.5. Classification Schemes for Implant Infection

6.609.6. Management of Periprosthetic Infection

6.609.7. The Future of Implant Design in Orthopedic Infection

6.609.8. Nanomolecular Permanent Modification of Biomaterials

6.609.9. Conclusions

6.610. Trends in Materials for Spine Surgery


6.610.1. Introduction

6.610.2. Anatomy and Physiology of the Spine

6.610.3. Spinal Fusion

6.610.4. Total Disc Arthroplasty

6.610.5. Annulus Repair

6.610.6. Concluding Remarks

6.611. Injectable Bone Cements for Spinal Column Augmentation: Materials for Kyphoplasty/Vertebroplasty


6.611.1. Introduction

6.611.2. History of Spinal Column Augmentation with Injectable Bone Cements and Currently Accepted Indications

6.611.3. Overview of Frequently Used Injectable Bone Cements for Spinal Augmentation

6.611.4. Clinical Results of Spinal Column Augmentation with Injectable Bone Cements

6.611.5. Complications in Spinal Column Augmentation

6.611.6. Future Directions and Conclusions

6.612. Biomaterials for Intervertebral Disc Regeneration


6.612.1. Overview of Intervertebral Repair: Current Strategies

6.612.2. Repair of the NP

6.612.3. Repair for the AF

6.613. Nucleus Replacement


6.613.1. Introduction

6.613.2. Ageing and Disk Injury

6.613.3. Treatment Options

6.613.4. Nucleus Replacement

6.613.5. Considerations for Evaluating Nucleus Replacements In Vitro and In Vivo

6.613.6. Summary

6.614. Wear: Total Intervertebral Disc Prostheses


6.614.1. Introduction to Total Disc Prostheses

6.614.2. Basic Anatomy and Biomechanics of the Spine

6.614.3. TDR Surgery

6.614.4. TDR Design

6.614.5. Evidence of TDR Wear

6.614.6. TDR Wear Simulation

6.614.7. Wear of Metal–PE TDR

6.614.8. Wear of Metal–Metal TDR

6.614.9. Wear of Alternative Material TDR

6.614.10. Biological Response to TDR Wear Debris

6.614.11. Conclusions

6.615. Intervertebral Disc


6.615.1. Background

6.615.2. IVD Structure and Function

6.615.3. IVD Preservation, Repair, and Regeneration

6.615.4. Future Challenges

6.616. Materials in Fracture Fixation


6.616.1. Fracture Healing

6.616.2. Basic Requirements of Biomaterials for Fracture Fixation Device

6.616.3. Devices Used in Fracture Fixation

6.617. Bone Tissue Grafting and Tissue Engineering Concepts

6.617.1. Introduction

6.617.2. Historical Overview

6.617.3. Polymeric Bone Graft Substitutes to Tissue Engineering

6.617.4. Bone Tissue Engineering

6.617.5. Animal Models for Assessing Effectiveness of Bone Tissue Engineering Strategies

6.618. Materials in Tendon and Ligament Repair


6.618.1. Introduction

6.618.2. Basic Properties of Tendon and Ligament

6.618.3. Augmentation of Scaffolds

6.618.4. Animal Models in Tendon and Ligament Research

6.618.5. Graft Materials

6.618.6. Clinical Application

6.618.7. Summary

6.620. Dental Graft Materials



6.620.1. Introduction

6.620.2. Categories of Dental Grafting Materials

6.620.3. Requirements and Novel Developments for Dental Graft Materials

6.620.4. Summary

6.621. Biomaterials and Their Application in Craniomaxillofacial Surgery


6.621.1. Introduction

6.621.2. Biomaterials and Implants in Craniomaxillofacial Surgery

6.621.3. Considerations and Future Applications

6.622. The Effect of Substrate Microtopography on Osseointegration of Titanium Implants



6.622.1. Introduction

6.622.2. In Vitro Studies

6.622.3. Mechanisms Mediating the Microtopography Effect

6.622.4. In Vivo Studies

6.622.5. Summary

6.623. Materials in Fixed Prosthodontics for Indirect Dental Restorations


6.623.1. General Introduction

6.623.2. Indirect Restorations

6.624. Cardiac Patch with Cells: Biological or Synthetic


6.624.1. Native Myocardium: Unique Tissue Properties

6.624.2. Clinical Indications for Myocardial Patch Repair

6.624.3. Patch Materials in Current Clinical Use

6.624.4. Experimental Synthetic Polymers

6.624.5. Strategies for Myocardial Tissue Engineering

6.624.6. In Vivo Maturation of a Cardiac Patch

6.624.7. Scientific Frontiers

6.624.8. Clinical Relevance and Perspectives

6.624.9. Summary

6.625. Long-Term Implantable Ventricular Assist Devices (VADs) and Total Artificial Hearts (TAHs)



6.625.1. Introduction

6.625.2. Configuration

6.625.3. LVAD Evolution

6.625.4. Partial Circulatory Support VADs

6.625.5. Total Artificial Heart

6.625.6. Conclusions

6.626. Cardiac Valves: Biologic and Synthetic



6.626.1. Introduction

6.626.2. Native Heart Valve Structure

6.626.3. Current Treatments

6.626.4. Ideal Scaffold

6.626.5. Synthetic Scaffolds

6.626.6. Decellularized Heart Valve Scaffolds

6.626.7. Naturally Derived Biomaterials of Nonvalvular Origin

6.626.8. Conclusion

6.627. Drug-Eluting Stents


6.627.1. Introduction

6.627.2. The Need for Coronary Stents: Problems with Baloon Angioplasty and Bare-Metal Stents

6.627.3. Development of DESs

6.627.4. First Generation DESs

6.627.5. Benefits of DES

6.627.6. Risks of DES

6.627.7. Second Generation DES

6.627.8. New Drug-Eluting Stents

6.627.9. Less Successful Medications on DES

6.627.10. Conclusions

6.628. Vascular Grafts


6.628.1. Introduction

6.628.2. Materials Used for Vascular Grafts: Current Clinical Experience

6.628.3. Host Responses to Implanted Biomaterials

6.628.4. Improving Clinical Outcomes and Future Concepts

6.628.5. Gene Therapy

6.628.6. Tissue-Engineered Blood Vessels

6.629. Cerebrospinal Fluid Shunts


6.629.1. Introduction

6.629.2. Hydrocephalus

6.629.3. Treatment of Hydrocephalus

6.629.4. Biocompatibility of Silicone Shunts

6.629.5. Infective Complications

6.629.6. Treatment of Shunt Infections

6.629.7. Prevention of Shunt Infections

6.629.8. Antimicrobial Shunt Catheters

6.629.9. Evaluation of Antimicrobial Catheters

6.629.10. Application of In Vitro Tests to Existing Shunt and EVD catheters

6.629.11. Clinical Studies on Antimicrobial Shunt and EVD catheters

6.629.12. Conclusions

6.630. Biomaterials for Spinal Cord Repair


6.630.1. An Introduction to Spinal Cord Injury

6.630.2. Biomaterials for Drug Delivery

6.630.3. Biomaterials for Cell Delivery

6.630.4. Future Outlook

6.631. Keratoprostheses


6.631.1. The Cornea and the Need for Corneal Replacement

6.631.2. Conclusion

6.632. Retina Reconstruction


6.632.1. The Retina

6.632.2. Ocular Diseases Associated with Retinal Degeneration

6.632.3. Retinal Reconstruction

6.632.4. Challenges in Retina Reconstruction

6.632.5. Scaffold Biocompatibility

6.632.6. Scaffold Fabrication

6.632.7. Conclusions

6.633. Development of Contact Lenses from a Biomaterial Point of View – Materials, Manufacture, and Clinical Application


6.633.1. Introduction

6.633.2. General Properties of Hydrogel Materials of Relevance to Contact Lenses

6.633.3. Conventional Hydrogel Contact Lens Materials

6.633.4. Silicone Hydrogel Contact Lens Materials

6.633.5. Classification of Soft Contact Lens Materials

6.633.6. Soft Contact Lens Manufacture

6.633.7. Clinical Ramifications of Polymer and Manufacturing Developments

6.633.8. Conclusions

Appendix A. Classification of Soft Lens Materials

6.634. Bioartificial Kidney


6.634.1. Overview of Renal Replacement

6.634.2. Membranes for Small-Solute Clearance

6.634.3. Renal Epithelial Cell Therapy

6.634.4. Preclinical Evaluation of Bioartificial Kidney

6.634.5. Clinical Evaluation of Bioartificial Kidney

6.634.6. Future Prospects

6.635. Surgical Adhesion and Its Prevention


6.635.1. Introduction

6.635.2. Formation of Adhesions and Major Areas of Concern

6.635.3. Barriers to Adhesion: Current Clinical Practice

6.635.4. Barriers to Adhesion: Current Research

6.635.5. Uses for Adhesion

6.635.6. Discussion

6.636. Suture Material: Conventional and Stimuli Responsive


6.636.1. Introduction

6.636.2. Properties of Suture Materials

6.636.3. Sutures

6.636.4. Staples

6.636.5. Surgical Needles

6.636.6. Conclusions

6.637. Staple Line Reinforcement Materials


6.637.1. Introduction

6.637.2. Staple Line Reinforcement

6.637.3. Reinforcement Materials

6.637.4. Discussion

6.638. Biomaterials for Hernia Repair

6.638.1. Introduction

6.638.2. History of Biomaterials in Hernia Surgery

6.638.3. Materials Used in Hernia Surgery

6.638.4. Hernia Surgery with Prostheses

6.638.5. Forces Acting on Hernia Meshes

6.638.6. Requirements for Hernia Meshes

6.638.7. Mesh Fixations

6.638.8. Potential Complications of Hernia Meshes

6.638.9. Conclusion and Future Perspectives


No. of pages:
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About the Editor

Paul Ducheyne

Paul Ducheyne is Professor of Bioengineering and Professor of Orthopaedic Surgery Research at the University of Pennsylvania, Philadelphia, USA. He is the Director of its Center for Bioactive Materials and Tissue Engineering. He also is Special Guest Professor at the University of Leuven, Belgium.

Paul Ducheyne has Materials Science and Engineering degrees from the K.U. Leuven. Belgium (M.Sc.: 1972; Ph.D.: 1976). With fellowships from the National Institutes of Health (International Postdoctoral Fellowship) and the Belgian American Educational Foundation (Honorary Fellowship), he performed postdoctoral research at the University of Florida.

Paul Ducheyne has organized a number of symposia and meetings, such as the Fourth European Conference on Biomaterials (1983), the Engineering Foundation Conference on Bioceramics (1986) which led to the New York Academy of Sciences publication: "Bioceramics, material characteristics versus in vivo behavior", and the Sixth International Symposium on Ceramics in Medicine (1993). He has lectured around the world and serves or has served on the editorial board of more than ten scientific journals in the biomaterials, bioceramics, bioengineering, tissue engineering, orthopaedics and dental fields. He has been a member of the editorial board, and then an associate editor of Biomaterials, the leading biomaterials journal, since its inception in the late seventies. He has authored more than 300 papers and chapters in a variety of international journals and books, and he has edited 10 books. He has also been granted more than 40 US patents with international counterparts. His papers have been cited about 7000 times; his ten most visible papers have been cited more than 2000 times.

Paul Ducheyne started his career in Europe. While at the K.U. Leuven, Belgium (1977 - 1983), he was one of the co-founders of the Post-Graduate Curriculum in Bioengineering. This program is now a full M.Sc. program in the School of Engineering and Applied Sciences. In those initial years, he was also chairman-founder of the chapter on Biomedical Engineering of the Belgian Engineering Society (Flemish section) and director of Meditek, the Flemish Government body created to promote Academia to Industry Technology Transfer in the area of Biomedical Engineering.

Paul Ducheyne founded Gentis, Inc., which focuses on breakthrough concepts for spinal disorders. Previously, he founded Orthovita (NASDAQ: VITA) in 1992 and served as Chairman of its Board of Directors until 1999. Orthovita focuses on bioceramic implant materials for orthopaedics.

Paul Ducheyne has been secretary of the European Society for Biomaterials, is Past President of the Society for Biomaterials (USA) and Past President of the International Society for Ceramics in Medicine. He has been recognized as a fellow of the American Association for the Advancement of Science (AAAS), fellow of the American Institute of Medical and Biological Engineering (AIMBE), and fellow of the International Association of Biomaterials Societies. He was the first Nanyang Visiting Professor at the Nanyang Institute of Technology, Singapore and he has received the C. William Hall Award from the Society for Biomaterials.

Many of Paul Ducheyne's trainees have become leaders of the next generation. Among his trainees are professors at the University of California at Berkeley, the University of Michigan, Columbia University, Georgia Institute of Technology, the K.U. Leuven (Belgium), etc... Among the six U.S. Associate Editors of the Journal for Biomedical Materials Research (the Journal of the Society for Biomaterials), three were his PhD students.

Affiliations and Expertise

University of Pennsylvania, Philadelphia, PA, USA

Paul Ducheyne

Paul Ducheyne is Professor of Bioengineering at the University of Pennsylvania, Philadelphia, USA, and a member of the Institute for Medicine and Engineering (IME) and the Center for Engineering Cells and Regeneration (CECR). Paul's research is focused in the investigation of mechanistic effects of materials on cellular functions, specifically cell attachment, proliferation, differentiation and extracellular matrix formation, especially with respect to biomaterials and tissue engineering. His lab works extensively with the interface zone between materials and cells and tissues, using both materials science techniques as well as life science methods. In addition, studies focus on the combined effects of microgravity and substrate material on cellular functions and on material surface modification and controlled release of growth factors. Several tissue engineering applications are pursued with orthopedic and dental applications. Specifically, his laboratory studies whether bone defects can be repaired with full return of mechanical function by treating defects with in vitro synthesized bone tissue.

Affiliations and Expertise

University of Pennsylvania, Philadelphia, USA

Kevin Healy

Kevin E. Healy, Ph.D. is the Jan Fandrianto Distinguished Professor in Engineering at the University of California at Berkeley in the Departments of Bioengineering and Materials Science and Engineering. He received a Bachelor of Science degree from the University of Rochester in Chemical Engineering in 1983. In 1985 he received a Masters of Science degree in Bioengineering from the University of Pennsylvania, and in 1990 he received a Ph.D. in Bioengineering also from the University of Pennsylvania. He was elected a Fellow of the American Institute of Medical and Biological Engineering in 2001. He has authored or co-authored more than 200 published articles, abstracts, or book chapters which emphasize the relationship between materials and the tissues they contact. His research interests include the design and synthesis of biomimetic materials that actively direct the fate of embryonic and adult stem cells, and facilitate regeneration of damaged tissues and organs. Major discoveries from his laboratory have centered on the control of cell fate and tissue formation in contract with materials that are tunable in both their biological content and mechanical properties. These materials find applications in medicine, dentistry, and biotechnology. He is currently an Associate Editor of the Journal of Biomedical Materials Research. He has served on numerous panels and grant review study sections for N.I.H. He has given more than 200 invited lectures in the fields of Biomedical Engineering and Biomaterials. He is a named inventor on numerous issued United States and international patents relating to biomaterials, and has founded several companies to develop materials for applications in biotechnology and regenerative medicine.

Affiliations and Expertise

University of California, Berkeley, Berkeley, CA, USA

Dietmar E. Hutmacher

Distinguished Professor Dietmar W. Hutmacher is the Director of the Centre of Regenerative Medicine and Director of the Australian Research Council Centre in Additive Biomanufacturing at the Queensland University of Technology (QUT). He holds a MBA from the Royal Henley Management College and a PhD from the National University of Singapore. His career so far has included extensive work in research and industry as well as in education and academia. Hutmacher has expertise in biomaterials, biomedical engineering, and tissue engineering & regenerative medicine (TE&RM), and is also among the pioneers in the field of 3D printing in Medicine. He has published more than 250 journal articles, 24 book chapters, and 10 edited books. In 2012 he was elected to join the highly esteemed International College of Fellows Biomaterials Science and Engineering, and to become one of the 23 founding members of the International Fellows of Tissue Engineering and Regenerative Medicine Society (TERMIS). In 2013, he received the highly prestigious Hans Fischer Senior Fellowship from the Technical University in Munich. He has been an Adjunct Professor at the Georgia Institute of Technology for over a decade. Serving on the editorial boards of leading journals in his fields, Hutmacher maintains strong relationships within the global biomaterials, TE&RM and cancer research community. Over the last 18 years, he has been invited to give more than 50 plenary and keynote lectures at national and international conferences, has served on 30 organising committees for international conferences, and chaired more than 80 sessions. A number of medical device and tissue engineering projects have been patented and commercialized under his mandate, and he is a founder of 5 spin off companies.

Affiliations and Expertise

Queensland University of Technology, Brisbane, QLD, Australia

David W. Grainger

David W. Grainger is the George S. and Dolores Dore´ Eccles Presidential Endowed Chair in Pharmaceutics and Pharmaceutical Chemistry, past Chair of the Department of Pharmaceutics and Pharmaceutical Chemistry, and Chair and Professor of Bioengineering at the University of Utah, USA.

Grainger received his Ph.D. in Pharmaceutical Chemistry from the University of Utah in 1987. With an Alexander von Humboldt Fellowship, he undertook postdoctoral research in biomembrane mimicry and assembly under Prof. Helmut Ringsdorf, University of Mainz, Germany.

Grainger’s research focuses on improving implanted medical device performance, drug delivery of new therapeutic proteins, nucleic acids and live vaccines, nanomaterials interactions with human tissues, low-infection biomaterials, and innovating diagnostic devices based on DNA and protein biomarker capture. He also has expertise in perfluorinated biomaterials and applications of surface analytical methods to biomedical interfaces, including surface contamination, micropatterns, and nanomaterials.

Grainger has published over 190 research papers at the interface of materials innovation in medicine and biotechnology, and novel surface chemistry. He has organized many international scientific symposia and chaired the Gordon Research Conference in Biomaterials and Tissue Engineering. He frequently lectures worldwide, including delivering many named, keynote, and plenary presentations.

Grainger serves on the editorial boards of four major journals in the biomedical materials field. He is currently a Council member at the National Institutes of Health, and has served on many national and international review panels, including the NIH’s Surgery and Bioengineering and Emerging Bioanalytical and Imaging Technologies Scientific Review Groups. He remains active on academic scientific advisory boards for diverse academic programs in the United States, Asia, and Europe, including major research centers at the Universities of Wisconsin-Madison and University of Washington, the AO Foundation and EMPA, Switzerland, the Charité, Germany, several other competence centers in Europe.. Grainger also sits on the scientific advisory boards for four biomedical companies and actively consults internationally with industries in applications of materials in biotechnologies and medicine.

His scientific and technical accomplishments are widely recognized, both at his institution and worldwide. Among several citations, Grainger is fellow of the American Association for the Advancement of Science (AAAS), the American Institute of Medical and Biological Engineering (AIMBE), and the International Union of the Societies of Biomaterials Science and Engineering. He has also been honored with the 2007 Clemson Award for Basic Research, Society for Biomaterials, and the 2005 American Pharmaceutical Research and Manufacturer’s Associa- tion’s award for ‘Excellence in Pharmaceutics’.

Affiliations and Expertise

University of Utah, Salt Lake City, UT, USA

C. James Kirkpatrick

C. James Kirkpatrick is Emeritus Professor of Pathology at the Johannes Gutenberg University of Mainz, Germany, having directed the Institute of Pathology from 1993-2015. Currently he is Senior Professor in the Cranio-Maxillofacial Surgery Clinic at the Goethe University of Frankfurt & Visiting Professor of Biomaterials & Regenerative Medicine at the University of Gothenburg, Sweden. He is also Honorary Professor at the Peking Union Medical College, Beijing and the Sichuan University, Chengdu, China.

Kirkpatrick is a graduate of the Queen’s University of Belfast and holds a triple doctorate in science and medicine (PhD: 1977; MD: 1982; DSc: 1992). Previous appointments were in pathology at the University of Ulm, where he did postdoctoral research in experimental pathology, Manchester University (Lecturer in Histopathology) and the RWTH Aachen (Professor of Pathology & Electron Microscopy).

On moving to Aachen in 1987, he established a cell culture laboratory which began using modern methods of cell and molecular biology to study how human cells react to biomaterials. Since then, his principal research interests continue to be in the field of biomaterials in tissue engineering and regenerative medicine, with special focus on the development of human cell culture techniques, including novel 3D coculture methodology for biomaterials and the application of modern molecular pathology techniques to the study of biofunctionality of biomaterials, including nanomaterials.

Kirkpatrick is author/coauthor of more than 500 publications in peer-reviewed journals and has given more than 500 invited presentations to scientific meetings worldwide. He has an H-index of 58 (Web of Science) and 68 (Google Scholar) and has been cited more than 17.000 times.

He is a former president of both the German Society for Biomaterials (2001–2005) and the European Society for Biomaterials (2002–2007) and served on the ESB council from 1995-2013. He was also a member of the Council of the European Chapter of the Tissue Engineering & Regenerative Medicine International Society (TERMIS-EU; 2006-2008; 2010-2012).

Kirkpatrick was a long-standing member of the editorial board of the premier journal Biomaterials (1996-2014) and also associate editor (2002-2014). He has also served as associate editor of the leading Journal of Pathology (2001–2006). In total, he serves or has served as an editorial board member of 18 international journals in pathology, biomaterials, and tissue engineering.

Kirkpatrick was the Scientific Programme Committee Chair for the 8th World Biomaterials Congress in Amsterdam in 2008.

Kirkpatrick is a member of the Scientific Advisory Board of a number of research institutes, centres of excellence and companies in biomaterials and regenerative medicine in Europe, as well as the Medical Technology Committee, Federal Ministry of Education & Research in Germany (BMBF) (2005-2008) and the German Federal Institute for Drugs & Medical Devices (BfArM)(since 2007).

Kirkpatrick has been recognized for his contributions. He is a Fellow of the Royal College of Pathologists, London and a Fellow of Biomaterials Science & Engineering (FBSE) of the IUS-BSE (International Union of Societies for Biomaterials Science & Engineering). He received the Research Prize of the State of Rhineland-Palatinate for Research on Replacement and Alternative Methods for Animal Research. He was the recipient of the George Winter Award from the European Society for Biomaterials (2008), and in 2010, he received, as first medical graduate, the Chapman Medal from the Institute of Materials, Minerals & Mining in London for “distinguished research in the field of biomedical materials”. In 2014 Kirkpatrick received the TERMIS-EU Career Achievement Award.

Affiliations and Expertise

Johannes Gutenburg University Medical Center, Mainz, Germany


"In a highly technical and vastly broad subject area, the key to managing (mastering) reputable information and facilitating new breakthroughs is through its preservation and organization by experts in the field. For students or researchers wanting a quick introduction or a working knowledge of an unfamiliar subfield of biomaterials, the assembled chapters will be much more valuable than the typical documents that rise to the top of keyword searches. The authors and editors should be commended for their efforts and congratulated on producing an impressive reference of lasting value. In this reviewer's opinion, it will be an essential reference for any library affiliated with graduate programs in the biomedical sciences. Summing Up: Highly recommended. Upper-division undergraduates and above." --Choice

"This is a huge body of work and I would suspect the price would preclude individual researchers from acquiring the set; however, this is a must have for libraries as an up-to-date reference for the current state-of–the-art information in this field as well as a fundamental reference tome for researchers seeking an introduction to the field." --Journal of Biomaterials Applications, February 2012