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 Woodhead Publishing Series in Biomaterials: Number 85

Tissue Engineering
Using Ceramics
and Polymers
Second Edition

Edited by
Aldo R. Boccaccini and Peter X. Ma

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Woodhead Publishing is an imprint of Elsevier
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 Contents

Contributor contact details xiii

Woodhead Publishing Series in Biomaterials xix
Foreword xxv
Preface xxvii

Part I General issues: materials 1

1 Ceramic biomaterials for tissue engineering 3

J. Huang, University College London, UK and S. Best,
University of Cambridge, UK
1.1 Introduction 3
1.2 Characteristics of ceramics 9
1.3 Microstructure of ceramics 12
1.4 Properties of ceramics 16
1.5 Processing of ceramics 22
1.6 Conclusions and future trends 27
1.7 References 28

2 Polymeric biomaterials for tissue engineering 35

G. Wei, Medtronic, Inc./Osteotech, USA and P. X. Ma,
University of Michigan, USA
2.1 Introduction 35
2.2 Polymeric scaffolds for tissue engineering 36
2.3 Polymeric scaffolds with controlled release capacity 51
2.4 Conclusions and future trends 58
2.5 Acknowledgements 59
2.6 References 59

3 Bioactive ceramics and glasses for tissue engineering 67

M. N. Rahaman, Missouri University of Science and
Technology, USA
3.1 Introduction 67
3.2 Scaffolds for tissue engineering 69

v
vi Contents

3.3 Bioactive ceramics 71

3.4 Properties of bioactive ceramics 77
3.5 Tissue engineering applications of bioactive ceramics 80
3.6 Bioactive glasses 83
3.7 Preparation and properties of bioactive glasses 86
3.8 Bioactive glasses in tissue engineering 91
3.9 Bioactive glass–ceramics 96
3.10 Bioactive composites 97
3.11 Conclusions and future trends 99
3.12 References 101

4 Biodegradable and bioactive polymer/inorganic phase

nanocomposites for bone tissue engineering (BTE) 115
V. Miguez-Pacheco, University of Erlangen-Nuremberg,
Germany, S. K. Misra, University of Birmingham, UK
and A. R. Boccaccini, University of Erlangen-Nuremberg,
Germany
4.1 Introduction 115
4.2 Composite materials for bone tissue engineering 116
4.3 Nanocomposites for tissue engineering 118
4.4 Electrospinning 122
4.5 Electrospun composite scaffolds based on natural polymers 122
4.6 Electrospun composite scaffolds based on synthetic polymers 127
4.7 Natural and synthetic polymer combinations 141
4.8 Conclusions and future trends 142
4.9 Acknowledgement 144
4.10 References 145

Part II General issues: processing, characterisation and

modelling 151

5 Nanoscale design in biomineralization for developing

new biomaterials for bone tissue engineering (BTE) 153
G. M. Luz and J. F. Mano, University of Minho, Portugal
5.1 Introduction 153
5.2 Materials and techniques for nanoscale design 161
5.3 Nanoparticles 162
5.4 Nanofibers and nanotubes 169
5.5 Nanopatterns 171
5.6 Drug-delivery systems 174
5.7 Nanocomposites 176
 Contents vii

5.8 Nanogels and injectable systems 179

5.9 Surface functionalization and templating 181
5.10 Conclusions and future trends 183
5.11 Acknowledgement 184
5.12 References 184

6 Characterisation of cells on biomaterial surfaces

and tissue-engineered constructs using microscopy
techniques 196
S. I. Anderson, University of Nottingham School of
Medicine, UK
6.1 Introduction 196
6.2 General considerations and experimental design 197
6.3 Confocal laser scanning microscopy (CLSM) 200
6.4 Combining techniques 215
6.5 Future trends 218
6.6 Sources of further information and advice 220
6.7 References 220

7 Materials for perfusion bioreactors used in tissue

engineering 224
I. Nettleship, University of Pittsburgh, USA
7.1 Introduction 224
7.2 The need for large volume cell culturing 226
7.3 Bioreactors for tissue engineering 228
7.4 The future of large bioreactors through in vitro mimicry
of the stem cell niche 241
7.5 Conclusions and future trends 244
7.6 Acknowledgements 246
7.7 References 246

8 Transplantation of engineered cells and tissues 252

J. Mansbridge, Histogen, Inc., USA
8.1 Introduction 252
8.2 The immune response to tissue engineered products 255
8.3 Generality of the resistance of tissue engineered products
to immune rejection 262
8.4 Testing and regulatory consequences 263
8.5 Comparison between autologous and allogeneic tissue
engineering 263
8.6 Conclusions and future trends 265
viii Contents

8.7 Sources of further information and advice 266

8.8 Acknowledgements 266
8.9 References 266

9 Carrier systems and biosensors for biomedical

applications 270
F. Davis and S. P. J. Higson, Cranfield University, UK
9.1 Introduction 270
9.2 Carrier systems 271
9.3 Commercial systems 284
9.4 Biosensors 284
9.5 Continuous monitoring 290
9.6 Immunosensors for point-of-care testing 291
9.7 Future trends 292
9.8 Conclusions 293
9.9 References 295

10 From images to mathematical models: intravoxel

micromechanics for ceramics and polymers 303
K. Luczynski, A. Dejaco and C. Hellmich, Vienna
University of Technology, Austria, V. Komlev, Russian
Academy of Sciences, Russia and W. Swieszkowski,
Warsaw University of Technology, Poland
10.1 Introduction 303
10.2 Conversion of voxel-specific computed tomography (CT)
data into material composition (volume fractions) 304
10.3 Conversion of material composition into voxel-specific
elastic properties 311
10.4 Intravoxel-micromechanics-enhanced finite element
simulations 322
10.5 Conclusions and future trends 335
10.6 Acknowledgements 335
10.7 References and further reading 336
10.8 Appendix: nomenclature 341

Part III Tissue and organ regeneration 345

11 Engineering of tissues and organs 347

S. J. Lee and A. Atala, Wake Forest University School of
Medicine, USA
11.1 Introduction 347
11.2 Native cells 348
 Contents ix

11.3 Alternate cell sources: stem cells for use in tissue engineering 349
11.4 Biomaterials 353
11.5 Cellular therapies 357
11.6 Tissue engineering of specific structures 360
11.7 Vascularization of engineered tissues 373
11.8 Conclusions and future trends 375
11.9 References 376

12 Myocardial tissue engineering 387

Q. Z. Chen, Monash University, Australia, S. E. Harding,
Imperial College London, UK and R. Rai and
A. R. Boccaccini, University of Erlangen-Nuremberg,
Germany
12.1 Introduction 387
12.2 Cell sources 389
12.3 Biomaterials-based strategies in myocardial tissue
engineering (MTE) 390
12.4 Potential scaffolding biomaterials 394
12.5 Conclusions and future trends 404
12.6 References and further reading 405

13 Kidney tissue engineering 414

A. Saito, Tokai University School of Medicine, Japan
13.1 Introduction 414
13.2 Limitations of hemodialysis (HD) as renal replacement
therapy 415
13.3 Concept and configuration of bioartificial kidneys 416
13.4 Early developments in bioartificial kidney design 418
13.5 Present developments in bioartificial tubule devices 418
13.6 Bioartificial tubule devices in the treatment of acute kidney
injuries with endotoxinaemia 427
13.7 Development of bioartificial renal tubule devices for
long-term treatment 431
13.8 Development of a bioartificial glomerulus 431
13.9 Future trends 433
13.10 References 436

14 Bladder tissue regeneration 439

F. Wezel and J. Southgate, University of York, UK
14.1 Introduction 439
14.2 Concepts, strategies and biomaterials for bladder
reconstruction and tissue engineering 442
x Contents

14.3 Review of past and current strategies in bladder

reconstruction 445
14.4 Cell conditioning in an external bioreactor 454
14.5 Future trends 456
14.6 Conclusions 457
14.7 References 457

15 Peripheral nerve tissue engineering 468

M. K. Kolar and P. J. Kingham, Umeå University,
Sweden
15.1 Introduction to the nervous system 468
15.2 Peripheral nerve injury and regeneration 471
15.3 Peripheral nerve repair 472
15.4 Nerve guidance conduits (NGCs) 473
15.5 Further structural optimisation of NGCs 481
15.6 Cultured cells for nerve repair 482
15.7 Conclusions 486
15.8 References 487

16 Tissue engineering of the small intestine 498

T. Ansari, Northwick Park Institute of Medical
Research, UK and S. M. Gabe, Imperial College
London, UK
16.1 Introduction 498
16.2 Approaches to tissue engineering of the small intestine 499
16.3 Scaffold selection 501
16.4 Guided tissue regeneration of the small intestine 505
16.5 Cell seeding sources 508
16.6 Combining cells and scaffolds 511
16.7 Growth factors 515
16.8 Conclusions and future trends 516
16.9 References 518

17 Skeletal muscle tissue engineering 524

D. Klumpp, R. E. Horch and J. P. Beier, University
Hospital of Erlangen, Germany
17.1 Introduction 524
17.2 Clinical and scientific applications 525
17.3 Characteristics of skeletal muscle 526
17.4 Potential scaffolds for skeletal muscle tissue engineering 528
17.5 Smart matrices 531
 Contents xi

17.6 Electrospun scaffolds in vivo/arteriovenous (AV)-loop

models in the rat 533
17.7 Conclusions and future trends 534
17.8 References 535

18 Cartilage tissue engineering 541

V. Salih, Plymouth University, UK
18.1 Introduction 541
18.2 Strategies for cartilage repair 542
18.3 The structure of articular cartilage 545
18.4 Biomaterials for articular cartilage replacement therapy 547
18.5 Conclusions 555
18.6 Future trends 556
18.7 Acknowledgement 556
18.8 References 557

19 Liver tissue engineering 565

J. Bierwolf and J.-M. Pollok, University Hospital Bonn,
Germany
19.1 Introduction 565
19.2 Liver diseases and current treatments 566
19.3 In vitro conditions for hepatocytes 569
19.4 In vitro analysis of hepatocyte function 572
19.5 Potential applications of engineered liver tissue 576
19.6 Conclusions and future trends 581
19.7 References 582

20 Collagen-based tubular constructs for tissue

engineering applications 589
C. E. Ghezzi, B. Marelli and S. N. Nazhat, McGill
University, Canada
20.1 Introduction 589
20.2 Current approaches to vascular tissue replacement and
regeneration 590
20.3 Current approaches to airway tissue replacement,
regeneration, and modelling 591
20.4 Type I collagen: the construction material 602
20.5 Cells: the construction workers 608
20.6 Culture conditions: the construction tools 612
20.7 Conclusions and future trends 619
20.8 References 619
xii Contents

21 Bioceramic nanoparticles for tissue engineering and

drug delivery 633
V. Sokolova and M. Epple, University of Duisburg-Essen,
Germany
21.1 Introduction 633
21.2 Ceramic nanoparticles 635
21.3 Nanoparticles for drug delivery 635
21.4 Nanoparticles for gene transfer (transfection) 637
21.5 Nanoparticles for gene silencing 638
21.6 Fluorescent nanoparticles for imaging 639
21.7 Nanoparticles in tissue engineering 641
21.8 Conclusions and future trends 642
21.9 References 642

22 Multifunctional scaffolds for bone tissue engineering

and in situ drug delivery 648
V. Mouriño and J. P. Cattalini, University of Buenos
Aires, Argentina, W. Li and A. R. Boccaccini, University
of Erlangen-Nuremberg, Germany and S. Lucangioli,
University of Buenos Aires, Argentina
22.1 Introduction 648
22.2 Scaffolds as drug carriers 650
22.3 Controlled release of therapeutic drugs for bone tissue
engineering 653
22.4 Conclusions and future trends 663
22.5 References and further reading 664

Index 676
 Contributor contact details

(* = main contact) Chapter 2

Editors G. Wei
Medtronic, Inc. /Osteotech
A. R. Boccaccini 201 Industrial Way West
Institute of Biomaterials Eatontown, NJ 07724, USA
University of Erlangen-Nuremberg
Cauerstr 6 E-mail: [email protected]
91058 Erlangen, Germany P. X. Ma*
E-mail: aldo.boccaccini@ University of Michigan
ww.uni-erlangen.de 1011 North University Ave
Ann Arbor, MI 48109-1078, USA
P. X. Ma
University of Michigan E-mail: [email protected]
1011 North University Avenue
Ann Arbor, MI 48109-1078, USA Chapter 3
E-mail: [email protected] M. N. Rahaman
Department of Materials Science and
Chapter 1 Engineering
Missouri University of Science and
J. Huang Technology
Department of Mechanical 223 McNutt Hall
Engineering Rolla, MO 65409, USA
University College London
Torrington Place E-mail: [email protected]
London WC1E 7JE, UK
E-mail: [email protected]
S. Best
Department of Materials Science
and Metallurgy
University of Cambridge
27 Charles Babbage Road
Cambridge CB3 0FS, UK

xiii
xiv Contributor contact details

Chapter 4 Chapter 6
V. Miguez-Pacheco S. I. Anderson
Institute of Biomaterials University of Nottingham School of
University of Erlangen-Nuremberg Medicine
Cauerstr 6 Division of Medical Sciences and
91058 Erlangen, Germany Graduate Entry Medicine
Royal Derby Hospital Centre
S. K. Misra
Derby DE22 3DT, UK
University of Birmingham
GEES E-mail: Susan.Anderson@
Edgbaston nottingham.ac.uk
Birmingham B15 2TT, UK
A. R. Boccaccini* Chapter 7
Institute of Biomaterials I. Nettleship
University of Erlangen-Nuremberg University of Pittsburgh
Cauerstr 6 Department of Mechanical
91058 Erlangen, Germany Engineering and Materials Science
E-mail: [email protected] Swanson School of Engineering
erlangen.de Pittsburgh, PA 15261, USA
E-mail: [email protected]
Chapter 5
G. M. Luz and J. F. Mano*
Chapter 8
3B’s Research Group – Biomaterials, J. Mansbridge
Biodegradables and Biomimetics Histogen, Inc.
University of Minho 10655 Sorrento Valley Road
Headquarters of the European San Diego, CA 92121, USA
Institute of Excellence on Tissue
Engineering and Regenerative E-mail: JonathanMansbridge@yahoo.
Medicine com; JMansbridge@HistogenInc.
AvePark, Zona Industrial da Gandra com
S. Cláudio do Barco
4806–909 Caldas das Taipas Chapter 9
Guimarães, Portugal F. Davis and S. P. J. Higson*
E-mail: [email protected] Cranfield Biotechnology Centre
School of Engineering
Cranfield University
Bedford MK43 0AL, UK
E-mail: [email protected];
[email protected]
 Contributor contact details xv

Chapter 10 Chapter 12
K. Luczynski, A. Dejaco and Q. Z. Chen
C. Hellmich* Monash University
Institute for Mechanics of Materials Wellington Road
and Structures Clayton, VIC3800, Australia
Vienna University of Technology
S. E. Harding
Karlsplatz 13/202
Imperial College London
A-1040 Vienna, Austria
Prince Consort Road
E-mail: christian.hellmich@tuwien. London SW7 2BP, UK
ac.at
R. Rai and A. R. Boccaccini*
V. Komlev Institute of Biomaterials
A. A. Baikov Institute of Metallurgy University of Erlangen-Nuremberg
and Materials Science Cauerstr 6
Russian Academy of Sciences 91058 Erlangen, Germany
Moscow, Russia
E-mail: aldo.boccaccini@
W. Swieszkowski ww.uni-erlangen.de
Faculty of Materials Science and
Engineering Chapter 13
Warsaw University of Technology
Politechniki Square 1 A. Saito
00-661 Warsaw, Poland Tokai University School of Medicine
Bohseidai
Isehara, Kanagawa 259-1193, Japan
Chapter 11
E-mail: [email protected]
S. J. Lee and A. Atala
Wake Forest Institute for
Regenerative Medicine Chapter 14
Wake Forest University School of F. Wezel and J. Southgate*
Medicine Jack Birch Unit of Molecular
Medical Center Boulevard Carcinogenesis
Winston-Salem, NC 27157-1094, Department of Biology
USA University of York
E-mail: [email protected]; York YO10 5DD, UK
[email protected] E-mail: jennifer.southgate@york.
ac.uk
xvi Contributor contact details

Chapter 15 Chapter 18
M. K. Kolar and P. J. Kingham* V. Salih
Department of Integrative Medical Plymouth University
Biology Peninsula School of Medicine &
Section for Anatomy Dentistry
Umeå University Portland Square
Umeå, SE-90187, Sweden Drakes Circus
Plymouth PL4 8AA, UK
E-mail: [email protected];
[email protected] E-mail: [email protected]

Chapter 16 Chapter 19
T. Ansari J. Bierwolf and J.-M. Pollok*
Department of Surgical Research University Hospital Bonn
Northwick Park Institute of Medical Department for General, Visceral,
Research Thoracic, and Vascular Surgery
Harrow, Middlesex, UK Sigmund-Freud-Straße 25
53105 Bonn, Germany
S. M. Gabe*
Department of Surgery and Cancer E-mail: Joerg.Pollok@ukb.
Imperial College London uni-bonn.de
London, UK
E-mail: [email protected] Chapter 20
C. E. Ghezzi, B. Marelli and
Chapter 17 S. N. Nazhat
Department of Mining and Materials
D. Klumpp, R. E. Horch and
Engineering
J. P. Beier
McGill University
Department of Plastic and Hand
MH Wong Building
Surgery
3610 University Street
University Hospital of Erlangen
Montreal, Quebec H3A 2B2, Canada
Friedrich-Alexander-University of
Erlangen-Nuernberg E-mail: [email protected]
Krankenhausstr. 12
Erlangen D-91054, Germany Chapter 21
E-mail: [email protected] V. Sokolova and M. Epple
Inorganic Chemistry and Center for
Nanointegration (CeNIDE)
University of Duisburg-Essen
Universitaetsstrasse 5-7
D-45117 Essen, Germany
E-mail: [email protected]