2nd Edition
Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine
Millions of patients suffer from end-stage organ failure or tissue loss annually, and the only solution might be organ and/or tissue transplantation. To avoid poor biocompatibility–related problems and donor organ shortage, however, around 20 years ago a new, hybridized method combining cells and biomaterials was introduced as an alternative to whole-organ and tissue transplantation for diseased, failing, or malfunctioning organs—regenerative medicine and tissue engineering. This handbook focuses on all aspects of intelligent scaffolds, from basic science to industry to clinical applications. Its 10 parts, illustrated throughout with excellent figures, cover stem cell engineering research, drug delivery systems, nanomaterials and nanodevices, and novel and natural biomaterials. The book can be used by advanced undergraduate- and graduate-level students of stem cell and tissue engineering and researchers in macromolecular science, ceramics, metals for biomaterials, nanotechnology, chemistry, biology, and medicine, especially those interested in tissue engineering, stem cell engineering, and regenerative medicine.
INTRODUCTION
Biomaterials and Manufacturing Methods for Scaffolds in Regenerative Medicine: Update 2015
Introduction
Biomaterials for Regenerative Medicine and Tissue Engineering
Scaffold Fabrication and Characterization
Concluding Remarks and Future Directions
References
CERAMIC AND METAL SCAFFOLDS
Biomineralized Matrices as Intelligent Scaffolds for Bone Tissue Regeneration
Introduction
CaP Biomaterials
CaP-Based Biomaterial-Assisted Osteogenic Differentiation of Stem Cells
CaP Matrices for Bone Tissue Engineering and Repair
CaP Mineral-Based Matrices as a Delivery Vehicle for Growth Factors and Genes
CaP-Assisted Stem Cell Osteogenesis and Bone Tissue Regeneration: Mechanistic Insights
Conclusions and Future Perspectives
References
Bioceramic and Composite Scaffolds in Drug Delivery and Bone Tissue Engineering
Introduction
Bioceramics
Nanotechnology in Bioceramics
Nanoceramics in Drug Delivery
Bone Tissue Engineering
Research Perspective
Basic Questions in Bone Tissue Engineering
Conclusions
References
Recent Development in Materials Innovation in Bone Tissue Regeneration
Overview
Materials’ Innovation
Microstructure and Morphology Optimization of Bioceramic-Based Bone Substitutes
Current Challenges and Future Directions in Bone Substitute Research
Conclusions
References
Carbonate Apatite Scaffolds for Regenerative Medicine
Introduction
Fabrication of Carbonate Apatite by Compositional Transformation Based on Dissolution-Precipitation Reaction Using a Precursor
Cell and Tissue Response to Carbonate Apatite
Porous Carbonate Apatite
Conclusions
References
Mg-Based Biodegradable Metals for Scaffolds
Introduction
Mg-Based Biodegradable Metals for Bone Scaffolds
Mg-Based Biodegradable Metals for Blood Vessel Scaffolds/Stents
Concluding Remarks
References
INTELLIGENT HYDROGELS
Functional DNA Building Blocks and Their Hydrogel Scaffolds for Biomedical Applications
Overview
DNA Nanobuilding Blocks
DNA Hydrogels
Functionalized DNA Hydrogels
Protein-Producing DNA Hydrogels
Conclusions
References
Recent Progress of Intelligent Hydrogels for Tissue Engineering
Introduction
History of Hydrogels
Properties of Hydrogel Scaffolds for Successful Tissue Engineering
Classification of Hydrogels
Conclusions
References
Polyanionic Hydrogels as Biomaterials for Tissue Engineering
Overview
Properties of Polyanionic Hydrogels
Polyanionic Hydrogels for Replacement of Biotissues
Polyanionic Hydrogels for Tissue Regeneration
Conclusions
References
Hyaluronic Acid–Based Hydrogel as a Scaffold for Tissue Engineering
Introduction
Characteristics of Hyaluronic Acid in Tissue Engineering
HA Derivatives
Fabrication of Hyaluronic Acid Hydrogels
Hyaluronic Acid–Based Hybrid Hydrogels
Conclusions and Outlook
References
Biologically Triggered Injectable Hydrogels as Intelligent Scaffolds
Introduction
Injectable Hydrogels as a Regenerative Scaffold
Enzyme-Triggered Hydrogels
Conclusions and Outlook
References
Cytocompatible and Reverse-Transformable Polymeric Hydrogel Matrices
Introduction
Polymer Hydrogel as an Artificial ECM
Physically Forming Crosslinkable Hydrogels
Stimuli-Responsive Hydrogels
Reversible and Spontaneously Forming Hydrogels
Rheological Properties of PMBV/PVA Hydrogels
Control of Cell Proliferation through PMBV/PVA Hydrogels
Differentiation Induction of Stem Cells Encapsulated in the PMBV/PVA Hydrogels
Conclusions and Future Perspectives
References
"Smart" Hydrogels in Tissue Engineering and Regenerative Medicine Applications
Introduction
Stimuli-Responsive Hydrogels: Types, Properties, and Applications
Processing of Hydrogels
Final Remarks and Future Trends
References
Cell-Encapsulating Polymeric Microgels for Tissue Repair
Introduction
Natural and Synthetic Polymers for Cell-Encapsulating Microgels
Fabrication Methods of Microgels for Cell Encapsulation
Design Considerations of Microgels for Cell Encapsulation
The Application of Cell-Encapsulating Microgels for Tissue Repair
Challenges for Clinical Translation
Summary and Future Perspectives
References
Injection Materials for the Larynx
Overview
Anatomy of the Vocal Fold
Pathologic Changes of the Vocal Fold in Glottal Insufficiency
General Principles of Injection Laryngoplasty for Vocal Fold Paralysis
General Characteristics of the Materials Currently Available for Vocal Fold Augmentation
Ideal Materials for Injection Laryngoplasty
Summary
References
Bionanocrystals in Tissue Engineering Strategies: Tools for Reinforcement, Nanopatterning, and/or Nanostructuring of Polymeric Scaffolds and Hydrogels
Introduction
Potential of PNCs in Tissue Engineering Strategies
Nanopatterned Surfaces
Nanostructured Films and Coatings
Porous Foam and Sponge Scaffolds
Fibrous Nanocomposities
Hydrogel Nanocomposites
Concluding Remarks
References
ELECTROSPINNING SCAFFOLDS
Porous Scaffolds Using Dual Electrospinning for in situ Cardiovascular Tissue Engineering
Introduction: Cardiovascular Tissue Engineering
Electrospinning
Cell Infiltration into Electrospun Scaffolds
Scaffold (An)isotropy
Controlling Scaffold Porosity
Mechanical Properties and Degradation Rate
Conclusions
References
Biofunctionalization of Electrospun Fibers for Tissue Engineering and Regenerative Medicine
Introduction
Electrospinning Process
Functionalization of Electrospun Fibers
Applications
Conclusions
References
Electrospun Fibrous Scaffolds
Introduction
Electrospinning Process
Advanced Fabrication Methods
Applications for Tissue Engineering
References
3D PRINTING FOR SCAFFOLDS
3D Printing of Tissue/Organ Scaffolds for Regenerative Medicine
Overview
The Modeling of Tissue/Organ Scaffolds
Material Selection
Technique Limitations
Conclusions and Prospects
References
3D Printing Technology Applied to Tissue Scaffolds
Introduction
3D Printing Methods Applied to Scaffolds
Summary
References
NANO-/BIOCONVERGENCE TECHNOLOGY FOR SCAFFOLDS
Nanomaterial-Assisted Tissue Engineering and Regenerative Medical Therapy
Introduction
Potential Risk of Nanomaterials
Conclusions and Future Perspectives
References
Application of Nanodevices in Sensing and Regenerative Medicine
Introduction
Fabrication of Nanodevices
Applications of Nanodevices
Conclusions
References
Micro-/Nanotech-Based Craniofacial Tissue Engineering
Overview
Micro-/Nanotech-Based Craniofacial Tissue Engineering
Conclusions
References
Carbon Nanotubes: A Kind of Novel Biomaterials for Scaffolds of Tissue Engineering
Introduction
Carbon Nanotubes in Bone Tissue Engineering
Nerve Tissue Engineering
The Others
References
ACELLULAR NATURAL MATRICES FOR SCAFFOLDS
Bacteriophage Scaffolds for Functional Assembly of Molecules and Nanomaterials
Overview
Phage Display
Phage Platform for Biological Applications
Genetic Modification of Phages to Create Inorganic Structures
Phage Display with Extended Genetic Codes
Conclusions
References
Intelligent Scaffold–Mediated Enhancement of the Viability and Functionality of Transplanted Pancreatic Islets to Cure Diabetes Mellitus
Overview
Scaffolds Fabricated with ECM Molecules Decellularized from the Pancreas
Natural Polymer–Based Scaffolds
Synthetic Polymer–Based Scaffold
Natural and Synthetic Polymer Composite–Based Scaffold
Conclusions
References
Extracellular Matrix–Derived Biomaterials: Molecularly Defined Ingredients and Processing Techniques
Introduction
Extracellular Matrix
Molecularly Defined Biomaterials
Techniques and Major Tools for Scaffolding
Summary and Future Perspectives
References
Biological-Derived Biomaterials for Stem Cell Culture and Differentiation
Introduction
Stem Cell Engineering
Biological-Derived Materials
Summary and Future Direction
References
Demineralized Dentin Matrix (DDM) Scaffolds for Alveolar Bone Engineering
History of the Demineralized Dentin Matrix
Characteristics of Scaffolds for Alveolar Bone Repair
Development of DDM Scaffolds
DDM Scaffolds with Recombinant Human BMP-2
Clinical Applications
Tooth Banks: Present and Future
References
Biomimetic Scaffold Fabrication for Tissue Engineering
Introduction
Biomimetic 2D Substrate Fabrication
Biomimetic 2D Substrate Modification
Biomimetic Surface Modification Methods
3D Scaffold Fabrication
Biomimetic Modification of 3D Scaffolds
Future Direction
Conclusions
References
SCAFFOLDS FOR TARGET ORGANS
Scaffolds for Tracheal Regeneration
Structure and Function of the Trachea
Tissue Engineering for Tracheal Stenosis
Scaffolds for Tracheal Regeneration
Cells
Bioreactors
Summary
References
Bladder Tissue Engineering
The Urinary Bladder: Function and Structure
Bladder Reconstruction and Augmentation
Materials for Bladder Tissue Engineering
Cell Seeding
Vascularization
Stem Cells in Bladder Tissue Engineering
Animal Studies and Clinical Trials
Future Perspectives: A Complete Bladder?
Scaffold Applications for Vascular Tissue Engineering
Introduction
Synthetic Biodegradable Polymer Scaffolds
Collagen and Other Biopolymer Scaffolds
Decellularized Tissue Scaffolds
Cell-Based Vascular Tissue Engineering
In situ "Cell Free" Vascular Tissue Engineering
Conclusions
References
Annulus Fibrosus Tissue Engineering: Achievements and Future Development
Introduction
Fundamentals of Annulus Fibrosus
Cells for Annulus Fibrosus Tissue Engineering
Scaffolds for Annulus Fibrosus Tissue Engineering
Growth Stimuli for Annulus Fibrosus Tissue Engineering
Concluding Remarks
References
Corneal Endothelium Regeneration: Basic Concepts
Introduction
Corneal Endothelium
Bioengineered Corneal Endothelium
Conclusions
References
DRUG DELIVERY SYSTEM FOR SCAFFOLDS
High-Throughput Screening of Extracellular Matrix–Based Biomaterials
Basic Principles
Relation to Materiomics
Future Perspectives
Classical Experiment 1: Biomaterial Array
Classical Experiment 2: Gene Expression Microarrays
References
Effect of Scaffolds with Bone Growth Factors on New Bone Formation
Introduction
Bone Lengthening in Preclinical Animal Studies
Growth Factor–/Stem Cell–Mediated Scaffolds for Bone Tissue Engineering
The Use of Scaffolds with or without Growth Factors and Cells for Clinical Trials
References
Drugs as Novel Biomaterials for Scaffolds
Overview
Drug Repositioning
Background and Structure of Fragmin and Protamine
Implications of Drug Repositioning in Tissue Engineering and Regenerative Medicine
Conclusions
References
FUTURE ENABLING TECHNOLOGY FOR SCAFFOLDS
Biocompatible Surface Coatings for Silicone-Based Implants
Overview
Surface Oxidation of Silicone Implants
Surface Coating with Bio-originated Materials
Surface Coating with Artificial Materials
Conclusions
References
Synthetic/PLGA Hybrid Scaffold for Tissue Regeneration: Update 2015
Introduction
Biomaterials for TERM
Hybrid and Composite Scaffold Biomaterials for TERM
PLGA/Natural Hybrid Scaffolds in Our Laboratory
Conclusions
References
Biomedical Applications of Silk Fibroin
Overview
Silk Fibroin Processing
Tissue Engineering Application of Silk Fibroin–Based Biomaterial
Conclusions
References
Tissue Fabrication and Regeneration by Cell Sheet Technology
Overview
Temperature-Responsive Culture Surface and Cell Sheets
Fabrication and Regeneration of 3D Tissues Using Cell Sheet Technology
Automation and Mechanization for Fabrication of 3D Tissues
Conclusions
References
Stem Cell Engineering Using Bioactive Molecules for Bone-Regenerative Medicine
Overview
First-Generation Bioactive Molecules: Proteins
Bioactive Molecules: Peptides
Bioactive Molecules: Small Molecules
Conclusions and Outlook
References
Biography
Gilson Khang is a professor at the Department of PolymerNano Science and Technology, Chonbuk National University (Korea) and a visiting professor at Tsinghua University, Peking University, and Zhejiang University (China) and the Wake Forest Institute of Regenerative Medicine (USA). Dr. Khang was elected as the founding Fellow of Tissue Engineering and Regenerative Medicine (FTERM) in 2012. He is a member of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) and a founding member of the TERMIS-AP chapter, of which he is also the continental chair since 2015. He is also an executive board member of TERMIS Global and since 2016 the TERMIS Global president-elect. From 2004 to 2009, Dr. Khang was editor-in-chief of Journal of Tissue Engineering and Regenerative Medicine. He has also served as co-editor-in-chief of International Journal of Tissue Regeneration, in addition to being on the editorial board of many reputed scientific journals. He has co-authored/edited 10 books and published around 550 original research papers and 200 editorials, reviews, and book chapters. His major scientific contribution has been to the analysis of natural/synthetic hybrid scaffolds to reduce host inflammation reactions, as well as the commercialization of tissue-engineered cartilage, bone, retinal pigment epithelium, and corneal endothelium.
This book is a comprehensive treatment of the techniques and technologies required to develop scaffolds for regenerative medicine applications. The authors are some of the leaders in the field, and together these chapters provide up-to-date information on this very important area."
--Prof. Robert M. Nerem, Georgia Institute of Technology, USA
"At long last, we have a comprehensive source for intelligent scaffolds for tissue engineering and regenerative medicine. Gilson Khang, a leader in the field, has partnered with other leading scientists in creating this book, which covers a wide range of materials and topics, from design and production to applications and functionality. This book is a must for the library of all individuals involved in the field."
--Prof. Anthony Atala, Wake Forest University, USA
"This book, written by prominent experts in the field, gives an excellent and timely introduction for those entering into the area of tissue engineering. Readers will also find it to be a good, up-to-date review that provides modern techniques for growth factor delivery, along with in vitro and in vivo outcomes, to facilitate understanding of the relationship between physiochemical structure and biological properties."
--Prof. Jöns Hilborn, Uppsala University, Sweden