Scaffolding in Tissue Engineering

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ISBN: 9781574445213 | 1574445219
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Copyright: 8/19/2005

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The growing interest in scaffolding design and increasing research programs dedicated to regenerative medicine corroborate the need for Scaffolding in Tissue Engineering. While certain books and journal articles address various aspects in the field, this is the first current, comprehensive text focusing on scaffolding for tissue engineering.Scaffolding in Tissue Engineering reviews the general principles of tissue engineering and concentrates on the principles, methods, and applications for a broad range of tissue engineering scaffolds. The first section presents an in-depth exploration of traditional and novel materials, including alginates, polysaccharides, and fibrillar fibrin gels. The following section covers fabrication technologies, discussing three-dimensional scaffold design, laboratory-scale manufacture of a cell carrier, phase separation, self-assembly, gas foaming, solid freeform fabrication, injectable systems, and immunoisolation techniques. Subsequent chapters examine structural and functional scaffold modification, composite scaffolds, bioactive hydrogels, gene delivery, growth factors, and degradation of biodegradable polymers. The final section explores various tissue engineering applications, comprising chapters on blood cell substitutes, and tissue engineering of nerves, the tendons, ligaments, cornea, cartilage andmyocardium, meniscal tissue.While providing a comprehensive summary of current knowledge and technologies, Scaffolding in Tissue Engineering gives readers insight into new trends and directions for scaffold development and for an ever-expanding range of tissue engineering applications.

Part I Scaffolding Materials

Chapter 1 Biologically Active Scaffolds Based on Collagen–GAG Copolymers

(10)

Ioannis V. Vannas

I. Introduction

(1)

II. Physicochemical Processes Leading to Synthesis of ECM Analogs

(2)

III. Synthesis of Tissues and Organs Using Scaffolds

(1)

IV. Structural Basis of Biological Activity

(1)

V. Scaffolds as Solid-State Enzymes

(2)

References

(3)

Chapter 2 Alginate for Tissue Engineering

(14)

Peter X. Ma

I. Introduction

(1)

II. Sources, Structures, and Properties

(2)

III. Various Biomedical Applications

(1)

A. Drug Delivery

(1)

B. Microencapsulation

(1)

IV. Tissue Engineering Scaffolds

(1)

V. Controlled Gelation and Uniform Tissue Engineering Constructs

(4)

VI. Conclusions

(1)

References

(6)

Chapter 3 Polysaccharide Scaffolds for Tissue Engineering

(18)

Tirtsa Ehrenfreund-Kleinman, Jacob Golenser, and Abraham J. Domb

I. Introduction

(1)

II. Chitosan

(3)

III. Alginate

(2)

IV. Glycosaminoglycans (GAGs)

(3)

A. Hyaluronic Acid (HA)

(2)

B. Heparin

(1)

C. Chondroitin Sulfate (CS)

(1)

V. Dextran

(1)

VI. Arabinogalactan

(2)

VII. Summary

(1)

References

(6)

Chapter 4 Role of Gelatin in the Release Carrier of Growth Factor for Tissue Engineering

(16)

Yasuhiko Tabata

I What is Tissue Engineering?

(3)

A. Factors Necessary for Tissue Engineering

(1)

B. Biodegradable Materials for Tissue Engineering

(2)

II Tissue Engineering Technology to Induce Tissue Regeneration

(1)

A. Role of Biomaterials in Tissue Engineering

(1)

III Controlled Release of Growth Factor from Biodegradable Hydrogel

(2)

A. Concept of Growth Factor Release

(1)

B. Characterization of Gelatin and Gelatin Hydrogel

(1)

IV Tissue Regeneration by Gelatin Hydrogels Incorporating Growth Factor

(6)

A. Angiogenesis

(4)

B. Bone Regeneration

(1)

C. Adipogenesis

(1)

V Concluding Remarks

(1)

References

(4)

Chapter 5 Fibrillar Fibrin Gels

(10)

Erin Grassi and Robert T. Tranquillo

I Introduction

(1)

II Structure, Biochemistry, and Rheological Properties of Fibrin

(1)

III Interaction of Cells with Fibrin

(1)

A. Fibroblasts in Fibrin

(1)

B. Smooth Muscle Cells in Fibrin

(1)

C. Other Cell Types

(1)

IV Challenges Using Fibrin

(1)

A. Controlling Fibrinolysis during Formation of New ECM

(1)

B. Removing (or Masking) Residual Fibrin

(1)

C. Effects of Fibrin Degradation Products (FDPs)

(1)

V. Tissue Engineering Applications

(3)

A. Fibrin as a Cell Delivery Vehicle

(1)

B. Artificial Ocular Surface

(1)

C. Skin Grafts

(1)

D. Bio-Artificial Arteries

(1)

E. Heart Valves

(1)

VI. Summary

(1)

References

(3)

Chapter 6 Photopolymerization of Hydrogel Scaffolds

(20)

Stephanie J. Bryant and Kristi S. Anseth

I. Introduction

(1)

II. Photopolymerization Mechanisms

(4)

A. Photoinitiation

(1)

1. Types of Initiators

(1)

2. Rate of Initiation

(1)

B. Propagation and Termination

(1)

C. Advantages/Disadvantages

(1)

III. Multifunctional Macromers

(4)

A. Types of Materials

(2)

B. Cross-Linking Mechanism

(1)

C. Macromer Properties

(1)

D. Degradation Mechanisms

(1)

IV. Hydrogel Properties and Characterization

(5)

A. Equilibrium Swelling Ratio

(1)

B. Gel Mechanics

(1)

C. Cross-Linking Density

(1)

D. Transport Properties

(1)

E. Mass Loss and Degradation

(2)

V. Cell Encapsulation

(1)

VI. Applications

(1)

A. Tissue Engineering

(1)

B. Drug Delivery

(1)

References

(3)

Further Reading

(1)

Chapter 7 Poly(ortho Esters)

(20)

Jorge Heller, John Barr, Devang T. Shah, Steve Y. Ng, Hui Rong Shen, and Brian C. Baxter

I. Introduction

(1)

II. Synthesis

(2)

III. Hydrolysis

(2)

IV. Control of Mechanical and Thermal Properties

(10)

A. Solid Devices

(1)

1. Polymer Storage Stability

(1)

2. Polymer Fabrication

(1)

3. Drug Release

(1)

a. Release of Bovine Serum Albumin from Extruded Strands

(1)

b. Delivery of DNA

100

(1)

c. Delivery of 5-Fluorouracil

100

(2)

B. Semisolid Devices

102

(1)

1. Polymer Molecular Weight Control

102

(1)

2. Polymer Stability

103

(1)

3. Polymer Erosion and Drug Release

103

(2)

V. Block Copolymers

105

(3)

A. Matrices for Protein Delivery

105

(1)

B. Micelles

105

(3)

References

108

(3)

Part II Scaffold Fabrication Technologies

Chapter 8 Salt Leaching for Polymer Scaffolds: Laboratory-Scale Manufacture of Cell Carriers

111

(14)

Joerg K.V. Tessmar, Theresa A. Holland, and Antonios G. Mikos

I. Introduction

111

(1)

II. Development of the Solvent-Casting and Particulate-Leaching Procedure

112

(1)

III. Scaffold Manufacturing

113

(4)

A. Salt and Polymer Preparation

113

(2)

B. Salt and Polymer Mixing

115

(1)

C. Polymer/Salt Construct Drying

116

(1)

D. Construct Modifications

116

(1)

E. Porogen Leaching

116

(1)

F. Scaffold Drying and Shaping

117

(1)

IV. Improvements in Scaffold Preparation and Processing

117

(5)

A. Mechanical Stability

118

(1)

B. Pore Interconnectivity

119

(2)

C. Scaffold Bioactivity

121

(1)

V. Directions for Future Research

122

(1)

VI. Conclusions

122

(1)

Acknowledgments

123

(1)

References

123

(2)

Chapter 9 Polymer Phase Separation

125

(14)

Victor J. Chen and Peter X. Ma

I Introduction

125

(1)

II Solid–Liquid Phase Separation

126

(2)

A. Preparation of Polymer Matrices

126

(2)

III Liquid–Liquid Phase Separation

128

(7)

A. Preparation of Continuous Network Polymer Matrices

129

(1)

B. Preparation of Polymer Matrices with a Nano-Fibrous Network

130

(1)

C. Preparation of Polymer Matrices with Platelet-Like Structures

131

(1)

D. Preparation of Nano-Fibrous Matrices with Macroporous Structures

132

(1)

1. Creating Macroporous Structures with Salt or Sugar Particles

132

(1)

2. Creating Macroporous Structures with Sugar Fibers

132

(1)

3. Creating Macroporous Structures with Paraffin Microspheres

133

(1)

4. Creating Macroporous Structures with Solid Freeform Fabrication

135

(1)

IV Conclusions

135

(1)

References

136

(3)

Chapter 10 Solid Freeform Fabrication of Tissue Engineering Scaffolds

139

(16)

Tien-Min G. Chu

I. Introduction

139

(2)

A. Background of SFF

140

(1)

B. Common Features of SFF

140

(1)

II. Scaffolds by SFF

141

(8)

A. Three-Dimensional Printing

141

(1)

1. The Technology

141

(1)

2. Application in Tissue Engineering Scaffolds

142

(1)

B. Fused Deposition Modeling

143

(1)

1. The Technology

143

(1)

2. Application in Tissue Engineering Scaffolds

144

(1)

C. Ink-Jet Printing and Indirect Casting

145

(1)

1. The Technology

145

(1)

2. Application in Tissue Engineering Scaffolds

145

(1)

D. Stereolithography

146

(1)

1. The Technology

146

(1)

2. Application in Tissue Engineering Scaffolds

147

(1)

E. Selective Laser Sintering

147

(1)

1. The Technology

147

(1)

2. Application in Tissue Engineering Scaffolds

147

(1)

F. Other Extrusion-Based Technologies

148

(1)

1. Robocast

148

(1)

2. Bioplotter

148

(1)

G. Protein and Cell Printing

149

(1)

1. Protein Printing

149

(1)

2. Cell and Organ Printer

149

(1)

III. Concluding Remarks

149

(1)

A. Connectivity at Wide Range of Porosity Levels

149

(1)

B. Versatility in Internal Architecture and External Geometry Control

150

(1)

C. Ability to Create Discrete Material and Design Domains

150

(1)

Acknowledgments

150

(1)

References

150

(5)

Chapter 11 Gas Foaming to Fabricate Polymer Scaffolds in Tissue Engineering

155

(14)

Yen-Chen Huang and David J. Mooney

I. Introduction

155

(1)

II. PLGA as a Tissue Engineering Material

156

(1)

III. The Gas Foaming Process

157

(1)

IV. Protein Delivery from Gas-Foamed PLGA Scaffolds

158

(4)

A. Angiogenesis

158

(1)

B. Bone Regeneration

159

(3)

V. Gene Delivery from Gas-Foamed PLGA Scaffolds

162

(2)

VI. Conclusions and Future Directions

164

(1)

References

165

(4)

Chapter 12 Injectable Systems for Cartilage Tissue Engineering

169

(20)

Christopher G. Williams and Jennifer H. Elisseeff

I. Introduction

169

(1)

II. Clinical Need for Injectable Tissue Engineering Systems

169

(1)

III. Tissue Engineering Strategies

170

(1)

IV. The Drive for Injectable Systems

170

(2)

V. In Situ Polymerization

172

(1)

VI. Thermoresponsive Hydrogels

172

(1)

VII. Ionic Gels

173

(1)

VIII. Fibrin Glue

174

(1)

IX. Collagen

175

(1)

X. Polyesters

175

(1)

XI. Poly(ethylene Glycol)

176

(1)

XII. Photopolymerization

176

(1)

XIII. Toxicity Study of Photoinitiators

177

(1)

XIV. Cartilage Tissue Engineering with Photopolymerizing Hydrogels

178

(2)

XV. Chondrogenesis of Mesenchymal Stem Cells in a Photopolymerizing Hydrogel

180

(4)

XVI. Conclusion

184

(1)

References

184

(5)

Chapter 13 Immunoisolation Techniques

189

(10)

Beth Anne Zielinski

I. Introduction

189

(1)

II. Theory and Capsule Format

190

(1)

III. Cell Sourcing

191

(1)

IV. Host Immune Responses to Encapsulated Cells

192

(1)

V. Conclusion

193

(1)

References

193

(4)

Appendix 1. Immunoisolation

197

(2)

Chapter 14 Self-Assembled Monolayers in Mammalian Cell Cultures

199

(18)

Xingyu Jiang, Jessamine Ng Lee, and George M. Whitesides

I. Introduction

199

(1)

II. Preparations of SAMS and Types of SAMS

200

(1)

A. SAMS of Alkanethiols on Gold and Silver

200

(1)

B. SAMS of Alkylsiloxanes

201

(1)

C. Other Types of SAMS

201

(1)

III. Characterization of SAMS

201

(1)

IV. Introduction of Functional Groups to the Surfaces of SAMS

202

(1)

A. The Synthesis of SAMS

203

(1)

B. In Situ Transformation

203

(1)

V. Chemical Transformations that Modify the Interactions between the SAM and the Substrate

203

(1)

A. Using Electrochemistry to Desorb SAMs

203

(1)

B. Oxidation of SAMs and Other Systems

204

(1)

VI. Interactions of Proteins with SAMs

204

(1)

A. Using SAMs as Model Surfaces to Study Adsorption of Proteins

204

(1)

B. "Inert" Surfaces

204

(1)

C. Non-Specific Adsorption of Proteins on Hydrophobic SAMs

204

(1)

D. Biospecific Adsorption of Proteins on SAMs

205

(1)

E. Electroactive Proteins on SAMs

205

(1)

F. Controlling the Orientation of Proteins on Surfaces

205

(1)

G. Other Biomolecules: DNA, Lipids, and Others

205

(1)

VII. Controlling Adsorption of Proteins and Patterning of Cells; Application of SAMs in Cell Biology

205

(3)

A. Controlling the Composition and Density of Ligands on the Surface

206

(1)

B. Soft Lithography, RCP, and Patterning Proteins

206

(1)

C. Patterning Cells

207

(1)

D. Dynamic Patterning of Cells and the Patterning of Multiple Proteins and Cells

207

(1)

E. Directional Control of Cell Migration

208

(1)

VIII. The Bridge to Tissue Engineering

208

(2)

A. Angiogenesis

208

(1)

B. Patterning of Neurons

208

(1)

C. Coculturing of Different Types of Cells

209

(1)

IX. Other Applications of SAMs in Biochemistry and Biotechnology

210

(1)

X. Conclusions and Summary

210

(1)

References

210

(7)

Chapter 15 PuraMatrix: Self-Assembling Peptide Nanofiber Scaffolds

217

(24)

Shuguang Zhang, Xiaojun Zhao, and Lisa Spirio

I. Introduction

218

(3)

A. Animal Derived ECM and Synthetic Scaffolds

218

(1)

B. PuraMatrix Peptide Nanofiber Scaffolds

219

(1)

1. Nanofiber Scale Synthetic ECM

219

(1)

2. Defined Three-Dimensional Microenvironments for Cell Biology

219

(1)

C. Three-Dimensional Cell Culture vs. Two-Dimensional

219

(1)

D. Nanoscale Fibers vs. Microscale

220

(1)

E. Ideal Synthetic Biological Scaffolds

220

(1)

II. Self-Assembling Peptides

221

(1)

A. Discovery and Development of Self-Assembling Peptides

221

(1)

1. Simple Repeating Units of Amino Acids Assemble into Nanofiber Scaffolds

221

(1)

2. Amenable to Design Incorporating Functional Motifs

221

(1)

B. Structural Properties of Self-Assembling Peptides

221

(1)

III. Peptide Nanofiber Scaffolds

222

(3)

A. EAK16-II

222

(1)

B. RADA16

222

(1)

C. KFE8 and KLD12

223

(2)

IV. PuraMatrix In Vitro Cell Culture Examples

225

(4)

A. Hepatocytes

225

(1)

B. Adult Liver Progenitor Cells

226

(1)

C. Chondrocytes Form Molded Cartilage in Cell Culture

226

(2)

D. Extensive Neurite Outgrowth and Active Synapse Formation on PuraMatrix

228

(1)

E. Organotypic Hippocampal Tissue Culture in PuraMatrix

229

(1)

F. Osteoblasts

229

(1)

V. Standard In Vitro Toxicology and Biocompatibility Studies

229

(2)

A. Cytotoxicity

229

(2)

B. Hemolysis

231

(1)

C. Coagulation Prothrombin Time

231

(1)

VI. In Vivo Biocompatibility and Toxicology Studies

231

(2)

A. ADME and Biodegradability

232

(1)

B. Rabbit Muscle Implant (2 Weeks)

232

(1)

C. Intracutaneous Reactivity

232

(1)

D. Rabbit Pyrogen

233

(1)

VII. Future Perspectives

233

(3)

A. Compatible with Bioproduction and Clinical Applications

233

(3)

B. Synthetic Origin, Clinical-Grade Quality, Clinical Delivery

236

(1)

C. Tailor-Made PuraMatrix

236

(1)

Acknowledgments

236

(1)

References

237

(4)

Part III Materials Modifications and Properties

Chapter 16 Polymer/Ceramic Composite Scaffolds for Bone Tissue Engineering

241

(12)

Guobao Wei and Peter X. Ma

I. Introduction

241

(1)

II. Polymer/Hydroxyapatite Composite Scaffolds

242

(2)

III. Polymer/Hydroxyapatite Nano Composite Scaffold

244

(3)

IV. Polymer/Apatite Composite Scaffold by Biomimetic Process

247

(1)

V. Conclusions

248

(1)

References

249

(4)

Chapter 17 Polymer/Calcium Phosphate Scaffolds for Bone Tissue Engineering

253

(12)

Cato T. Laurencin and Yusuf Khan

I. Introduction

253

(1)

II. Bone Grafts and Bone Graft Substitutes

253

(1)

III. Tissue Engineering

254

(2)

IV. Polymer/Calcium Phosphate Scaffolds

256

(5)

A. Why Calcium Phosphate

256

(1)

B. Hydroxyapatite

256

(2)

C. Other Calcium Phosphates

258

(1)

D. Formation of Calcium Phosphate Precipitates

259

(2)

V. Polymer/Ceramic Composites in the Marketplace

261

(1)

VI. Conclusions

261

(1)

References

261

(4)

Chapter 18 Hydroxyapatite/Collagen Scaffolds

265

(10)

Chang Du, Fu-Zhai Cui, and Klaas de Groot

I. Introduction

265

(1)

II. HA/Collagen Composite as Bone Substitute

265

(2)

III. Biomimetic HA/Collagen Scaffold

267

(3)

IV. Challenges and Perspectives

270

(1)

References

271

(4)

Chapter 19 Bioactive Hydrogels: Mimicking the ECM with Synthetic Materials

275

(8)

Jennifer L. West

I.The Extracellular Matrix — A Prototypical Bioactive Hydrogel

275

(1)

II. Modification of Hydrogel Materials with Cell Adhesion Ligands

275

(2)

III. Growth Factor Immobilization

277

(1)

IV. Proteolytically Degradable Hydrogels

278

(2)

V. Conclusions

280

(1)

References

280

(3)

Chapter 20 Albumin Modification

283

(18)

Sang Cheon Lee, Yoon Yeo, and Kinam Park

I. Introduction

283

(1)

II. Albumin Modifications with Heparin for Surface Coatings

284

(2)

A. Immobilization of Albumín–Heparin Conjugates

284

(1)

B. Surface Coating by Layer-by-Layer Assembly of Albumin and Heparin

284

(1)

C. Surface Coating by Polymerized Mixed Heparin–Albumin

285

(1)

III. Albumin-Cross-Linked Gels

286

(3)

A. PEG Hydrogels Cross-Linked with Albumin

286

(2)

B. Vinyl Polymer Hydrogels Cross-Linked with Albumin

288

(1)

C. Cross-Linked Heparinized Albumin Gels

289

(1)

IV. Albumin Modifications for Nano/Microspheres

289

(1)

A. Microspheres of Albumin–Heparin Conjugates

290

(1)

B. Nanospheres of Surface-Modified Albumin with PEG

290

(1)

V. Albumin Modifications for Carrier Systems

290

(1)

VI. Fabrication of Albumin Wafers Using a Coaxial Ultrasonic Atomizer

291

(2)

A. Principles of Ultrasonic Atomization

291

(1)

B. Fabrication of Albumin Wafers Using a Coaxial Ultrasonic Atomizer

292

(1)

VII. Summary

293

(1)

Acknowledgments

294

(1)

References

294

(7)

Chapter 21 Modified Alginates for Tissue Engineering

301

(16)

Yen-Chen Huang and David J. Mooney

I. Introduction

301

(2)

II. Alginate Modification

303

(3)

A. Control of Mechanical Properties

303

(1)

B. Controlling Degradability

304

(1)

C. Control of Cell Interactions

305

(1)

III. Application of Modified Alginates in Tissue Engineering

306

(5)

A. Regulation of Skeletal Muscle Cell Phenotype

306

(1)

B. Regeneration of Cartilage and Bone

306

(3)

C. Growth Factor Delivery

309

(2)

IV. Conclusion and Future Perspectives

311

(1)

References

312

(5)

Chapter 22 Polymeric Scaffolds for Gene Delivery and Regenerative Medicine

317

(18)

Aliasger K. Salem and Kam W. Leong

I. Tissue Engineering

317

(2)

II. Gene Delivery

319

(1)

A. Mechanism of Transfection

320

(1)

III. Materials for Gene Delivery and Scaffolds in Tissue Engineering

320

(2)

A. Natural Derived Polymers

321

(1)

B. Synthetic Polymers

322

(1)

IV. Design Criteria for Polymer Scaffolds in Tissue Engineering

322

(3)

A. Biocompatibility and Cell—Polymer Interactions

323

(1)

B. Pore Size and Morphology

323

(1)

C. Biodegradability

324

(1)

D. Scaffolds as Controlled Release Devices

324

(1)

V. Gene Delivery from Scaffolds

325

(2)

VI. Fabrication Methods

327

(1)

VII. Conclusions

328

(1)

References

328

(7)

Chapter 23 Degradation of Biodegradable Aliphatic Polyesters

335

(20)

Suming Li

I. Introduction

335

(2)

II. Degradation Mechanism

337

(3)

III. Degradation Characteristics

340

(8)

A. Polymer Morphology

340

(4)

B. Polymer Composition

344

(1)

C. MW and MW Distribution

345

(1)

D. Size and Porosity

346

(1)

E. Additives

347

(1)

F. Others

348

(1)

IV. Conclusion

348

(1)

References

348

(7)

Part IV Tissue Engineering Applications

Chapter 24 Biomaterials for Genitourinary Tissue Engineering

355

(16)

Priyabrata Mukherjee and Anthony Atala

I. Introduction

355

(1)

II. Importance of Biomaterials

355

(1)

III. Design and Selection of Biomaterials

356

(1)

IV. Classification of Biomaterials

357

(2)

V. Biomaterials Utilized to Engineer Genitourinary Tissues

359

(5)

A. Kidneys

359

(1)

B. Ureters

359

(1)

C. Bladder

360

(1)

D. Urethra

361

(2)

E. Genital Tissue

363

(1)

F. Injection Therapies

363

(1)

VI. Future Directions

364

(1)

References

365

(6)

Chapter 25 Engineered Blood Vessel Substitutes

371

(14)

Jan P. Stegemann, Shaneen L. Rowe, and Robert M. Nerem

I. Introduction

371

(1)

II. Blood Vessel Structure and Function

372

(2)

III. Endothelialization Strategies

374

(1)

IV. Scaffolding Strategies

375

(5)

A. Degradable Synthetic Scaffolds

375

(2)

B. Naturally-Derived Scaffolds

377

(2)

C. Cell-Secreted Scaffolds

379

(1)

V. Biological Response to Scaffold

380

(1)

VI. Summary and Future Directions

381

(1)

Acknowledgments

381

(1)

References

381

(4)

Chapter 26 Tissue Engineering of Tendons and Ligaments

385

(28)

Changeting Guo and Myron Spector

I. Introduction

386

(1)

II. Tendon and Ligament Anatomy, Composition, and Function

387

(3)

A. The Cell Types

387

(1)

B. The Extra-Cellular Matrix (ECM)

387

(2)

C. The Surrounding and Supporting Tissue

389

(1)

D. Insertion into Bone

389

(1)

E. Function — Biomechanics

389

(1)

F. Differences between Tendons and Ligaments

390

(1)

III. Healing Processes

390

(3)

A. Is there Any Part of the Tendon that Can Self-Regenerate?

391

(1)

B. Embryological vs. Adult Healing

391

(1)

C. Source of Reparative Cells

392

(1)

D. Normal Tendons and Ligaments vs. Scar Tissue

393

(1)

IV. Tendon and Ligament Tissue Engineering: Basic Considerations

393

(2)

A. Candidate Cells

394

(1)

B. Roles of the Scaffold

394

(1)

V. In Vitro Tissue Engineering Investigations Employing Biomaterial Scaffolds

395

(3)

A. Evaluation of Biomaterials as Cell-Seeded Constructs

396

(1)

B. Collagen Fibers

396

(1)

C. Silk–Fiber Matrix

397

(1)

D. Seeding of Cultured Tenocytes into Porous Collagen–GAG Matrices

397

(1)

VI. Animal Studies Implementing Tissue Engineering Scaffolds

398

(5)

A. Animal Models: Entubulation

398

(1)

B. Fibrous Scaffolds

399

(1)

1. Collagen Fiber Scaffold

399

(1)

2. Mesenchymal Stem Cell-Seeded Knitted PLGA Fiber Scaffold

399

(1)

3. Tenocyte-Seeded Polyglycolic Acid Fiber Mesh

400

(1)

C. Sponge-Like Scaffolds

400

(1)

1. Collagen–GAG Matrices Contained within a Tube

400

(2)

D. Gel-Like Scaffolds

402

(1)

VII. Effects of Growth Factors

403

(1)

VIII. Use of Gene Therapy for Tendon/Ligament Tissue Engineering

404

(1)

IX. Effect of External Factors on Tendon Regeneration

405

(1)

X. Use of Bioreactors for Tendon/Ligament Tissue Engineering

406

(1)

Acknowledgments

406

(1)

References

406

(7)

Chapter 27 Tissue Engineering of the Cornea

413

(12)

May Griffith, Fengfu Li, Chris Lohmann, Heather D. Sheardown, Shigeto Shimmura, and David J. Carlsson

I. Introduction

413

(1)

II. The Need for TE Corneas

413

(1)

III. Replacements for Human Corneas

414

(1)

IV. Synthetic Scaffolds and Keratoprostheses

415

(2)

V. Cell-Based Corneal Model Structures

417

(1)

VI. Biosynthetic Matrix Replacements as Scaffolds

418

(3)

VII. Tissue Engineering of the Cornea: Are We there yet?

421

(1)

References

421

(4)

Chapter 28 Materials Employed for Breast Augmentation and Reconstruction

425

(12)

Parul Natvar Patel and Charles W. Patrick, Jr.

I. Introduction

425

(1)

II. Anatomy of the Breast

425

(1)

III. Clinical Impetus

426

(1)

IV. Standard of Care

427

(2)

A. Implants and Expanders

427

(1)

B. Autologous Tissue

428

(1)

V. Overall Tissue Engineering Strategy

429

(1)

VI. Materials as Scaffolds

430

(3)

A. Natural and Synthetic Polymer Foams and Non-Woven Meshes

430

(1)

B. Hydrogels

431

(2)

VII. Materials as Delivery Vehicles for Adipogenic Factors

433

(1)

VIII. Future Considerations

433

(1)

References

433

(4)

Chapter 29 Scaffolding in Periodontal Engineering

437

(18)

Orasa Anusaksathien, Qi-ming Jin, Peter X. Ma, and William V. Giannobile

I. Challenges in the Treatment of Periodontal Alveolar Bone Defects

437

(1)

II. Importance of Delivery Devices for Periodontal Tissue Engineering

438

(2)

III. Scaffolding Devices Used for Periodontal Tissue Engineering

440

(4)

A. Naturally Derived Scaffolds

440

(1)

1. Allograft–Xenograft Biomaterials

440

(1)

2. Cell Occlusive Devices and Collagen-Based Materials

440

(1)

3. Hyaluronic Acid-Based Scaffolds

442

(1)

4. Calcium Phosphate-Based Ceramics

443

(1)

B. Synthetic Scaffolds

443

(1)

1. Poly(lactide-coglycolide)

443

(1)

IV. Protein Delivery for Periodontal Tissue Engineering

444

(1)

V. Cell Delivery for Periodontal Engineering

445

(1)

VI. Gene Delivery in Periodontal Tissue Engineering

446

(1)

VII. Future Applications

446

(1)

Acknowledgments

446

(1)

References

446

(9)

Chapter 30 Tissue Engineering of Craniofacial Structure

455

(18)

Kacey G. Marra, Mark P. Mooney, and Jeffrey O. Hollinger

I. FDA-Approved Biodegradable Polymers

455

(4)

A. Poly(glycolic Acid)

455

(1)

B. Poly(lactic Acid)

455

(1)

C. Poly(lactic-co-glycolic Acid)

456

(1)

D. Other Biodegradable and Native Polymers

456

(3)

II. Growth Factors and Bone Regeneration

459

(4)

A. Bone Morphogenetic Proteins

459

(1)

B. Insulin-Like Growth Factors

460

(1)

C. Transforming Growth Factors

460

(1)

D. Fibroblast Growth Factors

461

(2)

E. Platelet-Derived Growth Factors

463

(1)

III. Growth Factor Encapsulation

463

(1)

IV. Conclusions

464

(1)

Acknowledgments

465

(1)

References

465

(8)

Chapter 31 Hemoglobin-Based Red Blood Cell Substitutes

473

(8)

Thomas Ming Swi Chang

I. Introduction

473

(1)

II. First-Generation Blood Substitutes

473

(4)

A. Polyhemoglobin

473

(1)

B. Glutaraldehyde Cross-Linked Human Pyridoxalated Polyhemoglobin

474

(1)

C. Glutaraldehyde Cross-Linked Bovine Polyhemoglobin

475

(1)

D. Other Types of Modified Hemoglobin

476

(1)

III. Second-Generation Blood Substitutes

477

(1)

A. Polyhemoglobin–Superoxide Dismutase–Catalase in Ischemia Reperfusion

477

(1)

IV. Third-Generation Blood Substitutes

477

(1)

A. Hemoglobin Lipid Vesicles

477

(1)

B. Nanodimension Artificial Red Blood Cells with Biodegradable Polymeric Membrane

477

(1)

Acknowledgments

478

(1)

References

478

(3)

Chapter 32 Nerve Regeneration

481

(20)

Erin Lavik and Robert Langer

I. Scaffolds for the PNS

482

(2)

A. The Structure of the PNS

482

(1)

B. Previous Treatments for Repair of the PNS

482

(1)

C. Scaffolds for Repair in the PNS

483

(1)

II. Scaffolds for the CNS: The Spinal Cord

484

(2)

A. Basic Anatomy of the Spinal Cord (an Engineering View)

484

(1)

B. Results of Spinal Cord Injury

485

(1)

III. Approaches to Treatment, Repair, and Regeneration

486

(6)

A. Drug Interventions

486

(1)

1. Methylprednisolone

486

(1)

2. Growth Factors

486

(1)

3. Role of Other Drugs and Antibodies

486

(1)

B. Cell Therapies for the Spinal Cord

487

(1)

1. Schwann Cells

487

(1)

2. Olfactory Ensheathing Cells

487

(1)

3. Stem Cells

488

(1)

a. Embryonic Stem Cells

488

(1)

b. Neural Stem Cells

489

(1)

C. Role of Surface Chemistry: The Extra Cellular Matrix

489

(1)

D. Scaffolds in the Spinal Cord

490

(1)

1. Axonal Guidance: Utilizing the Regenerative Potential of the PNS to Induce Regeneration in the CNS

490

(1)

E. A New Approach to Spinal Cord Repair: Tissue Engineering

491

(1)

IV. Scaffolds for the CNS: The Brain

492

(1)

V. The Future for Scaffolds in the Nervous System

492

(1)

References

492

(9)

Chapter 33 Functional Tissue Engineering of Cartilage and Myocardium: Bioreactor Aspects

501

(30)

Milica Radisic, Bojana Obradovic, and Gordan Vunjak-Novakovic

I. Introduction

501

(2)

II. Tissue Engineering Bioreactors

503

(4)

III. Bioreactor Cultivation of Engineered Cartilage

507

(6)

A. Orbitally Mixed Dishes

507

(4)

B. Static Flasks, Mixed Flasks, Rotating Vessels, and Perfused Cartridges

511

(1)

C. Mechanical Stimulation

511

(1)

D. Interactions of Growth Factors and Hydrodynamic or Mechanical Stimulation

511

(1)

E. Controlled Bioreactor Studies

512

(1)

IV. Bioreactor Cultivation of Engineered Cardiac Tissue

513

(4)

A. Static and Orbitally Mixed Dishes

513

(1)

B. Mixed Flasks

514

(1)

C. Rotating Vessels

515

(1)

D. Perfused Cartridges with Interstitial Flow of Medium

515

(1)

E. Mechanical Stimulation

516

(1)

F. Electrical Stimulation

517

(1)

V. Case Studies

517

(9)

VI. Summary

526

(1)

Acknowledgments

526

(1)

References

526

(5)

Chapter 34 Stem Cells in Tissue Engineering

531

(14)

Valor Prisk and Johnny Huard

I. Introduction

531

(1)

II. Stem Cells

531

(2)

III. Gene Therapy

533

(1)

IV. Stem Cell Based Therapy

534

(1)

V. Musculoskeletal System

535

(3)

A. Bone Healing

535

(1)

B. Intraarticular Disorders

536

(1)

C. Skeletal Muscle

537

(1)

VI. Cardiovascular System

538

(1)

VII. Urogenital System

538

(1)

VIII. Conclusion

539

(1)

References

539

(6)

Chapter 35 Osteochondral Tissue Engineering — Regeneration of Articular Condyle from Mesenchymal Stem Cells

545

(20)

Adel Alhadlaq and Jeremy J. Mao

I. Introduction

545

(1)

II. Computer-Aided Scaffolding and Molding Approaches

546

(3)

III. Scaffold Materials and Design

549

(1)

IV. Mechanical Modulation of Chondrogenic and Osteogenic Process

550

(2)

V. Representative Tissue Engineering of Human Articular Condyles from Adult Stem Cells

552

(7)

VI. Conclusions and Future Perspectives

559

(1)

Acknowledgments

559

(1)

References

559

(6)

Chapter 36 Tissue Engineered Meniscal Tissue

565

(20)

Mark A. Randolph and Thomas J. Gill

I. Introduction

565

(1)

II. Anatomy and Composition

566

(1)

III. Function

567

(2)

IV. Meniscal Cells

569

(1)

V. Cell Sources for Tissue Engineering

569

(1)

VI. Scaffolds

570

(8)

A. Synthetic Polymers

571

(1)

B. Biological Scaffolds

572

(3)

C. Hydrogel Scaffolds

575

(2)

D. Inert Nonresorbable Materials

577

(1)

VII. Conclusions

578

(1)

References

578

(7)

Chapter 37 Tissue Engineering for Insulin Replacement in Diabetes

585

(24)

Amy S. Lewis and Clark K. Colton

I. Introduction

585

(1)

II. Exogenous Insulin Delivery

586

(1)

III. Tissue Sources

587

(2)

A. Xenogeneic Islets

587

(1)

B. Stem Cells

588

(1)

C. Cell Lines

588

(1)

IV. Immune Destruction of Islets

589

(2)

A. Auto-Immune Reactions

589

(1)

B. Allograft Reactions

590

(1)

C. Xenograft Reactions

590

(1)

D. Inflammatory Reactions

590

(1)

V. Engineering Approaches to Immunoprotection of Islets

591

(8)

A. Extravascular Macroencapsulation Devices

591

(2)

B. Microencapsulation

593

(1)

1. Alginate and Poly-L-lysine

593

(1)

2. Alginate Alone

594

(1)

3. Other Alginate Systems

595

(1)

4. Other Microencapsulation Materials

595

(1)

5. In Vivo Performance of Microencapsulated Islets

596

(1)

C. Mass Transfer

596

(1)

1. Mass Transfer Limitations

596

(1)

2. Methods to Improve Mass Transfer

598

(1)

D. NMR Spectroscopy and Imaging

599

(1)

VI. Future Directions

599

(1)

References

600

(9)

Chapter 38 Three-Dimensional Tissue Fabrication: Application in Hepatic Tissue Engineering

609

(16)

Valerie Liu Tsang and Sangeeta N. Bhatia

I. Introduction to Hepatic Tissue Engineering

609

(1)

II. Overview of Three-Dimensional Tissue Fabrication

610

(1)

III. 3D Scaffold Fabrication Methods

611

(5)

A. Heat-Based Scaffold Fabrication

611

(2)

B. Light-Based Scaffold Fabrication

613

(2)

C. Adhesive-Based Scaffold Fabrication

615

(1)

D. Molded Scaffold Fabrication

616

(1)

IV. Fabrication of Cellular Structures

616

(2)

V. Fabrication of Hybrid (Cell/Scaffold) Constructs

618

(1)

A. Cell-Laden Hydrogels

618

(1)

B. Three-Dimensional Photopatterning of Cell-Laden Hydrogels

618

(1)

VI. Summary and Future Directions

619

(1)

Acknowledgments

620

(1)

References

621

(4)

Index

625

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Scaffolding in Tissue Engineering

Summary

Table of Contents

Supplemental Materials