Tissue Engineering Using Ceramics and Polymers

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Woodhead Publishing Limited and Maney Publishing Limited on behalf of
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 Contents

Contributor contact details xiii

Introduction xix

Part I General issues

1 Ceramic biomaterials 3
J HU A N G , University College London, UK and
S M BE S T , 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 26
1.7 Future trends 26
1.8 References 27

2 Polymeric biomaterials 32
G WE I and P X MA , The University of Michigan, USA
2.1 Introduction 32
2.2 Polymeric scaffolds for tissue engineering 33
2.3 Polymeric scaffolds with controlled release capacity 43
2.4 Conclusions 47
2.5 References 47

3 Bioactive ceramics and glasses 52

J R JO N E S , Imperial College, London, UK
3.1 Introduction 52
3.2 Synthetic hydroxyapatite 54
3.3 Bioactive glass 58
vi Contents

3.4 Glass-ceramics 67
3.5 Conclusions 67
3.6 References 68

4 Biodegradable and bioactive polymer/ceramic

composite scaffolds 72
S K MI S R A and A R BO C C A C C I N I , Imperial College
London, UK
4.1 Introduction 72
4.2 Biodegradable polymers and bioactive ceramics 74
4.3 Composite material approach 78
4.4 Materials processing strategies for composite scaffolds 80
4.5 Case studies 83
4.6 Conclusions and future trends 87
4.7 References and further reading 89

5 Transplantation of engineered cells and tissues 93

J MA N S B R I D G E , Tecellact LLC, USA
5.1 Introduction 93
5.2 Rejection of tissue-engineered products 95
5.3 Testing and regulatory consequences 102
5.4 Generality of the resistance of tissue-engineered products to
immune rejection 102
5.5 Manufacturing consequences 103
5.6 Conclusions and future trends 104
5.7 Sources of further information and advice 105
5.8 Acknowledgements 105
5.9 References 105

6 Surface modification to tailor the biological

response 108
K SH A K E S H E F F and G TS O U R P A S , University of
Nottingham, UK
6.1 Introduction 108
6.2 The biochemistry of cell interactions with the ECM 108
6.3 The need for surface modification of scaffolds 114
6.4 General strategies for surface modification 115
6.5 Examples from the literature 116
6.6 Future trends 123
6.7 References 124
 Contents vii

7 Combining tissue engineering and drug delivery 129

N TI R E L L I and F CE L L E S I , University of Manchester, UK
7.1 Introduction 129
7.2 Growth factor (GF) delivery 131
7.3 Signalling molecules in solution (parenteral administration) 135
7.4 Signalling molecules physically entrapped in a matrix 136
7.5 Signalling molecules released from a bound state 147
7.6 References 149

8 Carrier systems and biosensors for biomedical

applications 153
F DA V I S and S P J HI G S O N , Cranfield University, UK
8.1 Introduction 153
8.2 Carrier systems 153
8.3 Commercial systems 161
8.4 Biosensors 162
8.5 Continuous monitoring 167
8.6 Future trends 169
8.7 Conclusions 170
8.8 References 171

9 Characterisation using X-ray photoelectron

spectroscopy (XPS) and secondary ion
mass spectrometry (SIMS) 175
A J UR Q U H A R T and M R AL E X A N D E R , University of
Nottingham, UK
9.1 Introduction 175
9.2 X-ray photoelectron spectroscopy (XPS) 177
9.3 Static secondary ion mass spectrometry (SIMS) 187
9.4 Specific sample preparation and acquisition procedures 193
9.5 Conclusions 197
9.6 Future trends 198
9.7 Acknowledgement 199
9.8 References 199

10 Characterisation using environmental scanning

electron microscopy (ESEM) 204
A M DO N A L D , University of Cambridge, UK
10.1 Introduction 204
10.2 The instrument: a comparison with CSEM 204
10.3 Static experiments 210
10.4 Dynamic experiments 212
viii Contents

10.5 Dual beam instruments ± an emerging technique 218

10.6 Potential and limitations 219
10.7 Conclusions 221
10.8 References 221

11 Characterisation of cells on tissue engineered

construsts using imaging techniques/microscopy 226
S I AN D E R S O N , University of Nottingham, UK
11.1 Introduction 226
11.2 General considerations and experimental design 226
11.3 CLSM 228
11.4 Combining techniques 241
11.5 Future trends 244
11.6 References 245

12 Characterisation using Raman micro-spectroscopy 248

I NO T I N G H E R , University of Nottingham, UK
12.1 Introduction 248
12.2 Principles of Raman spectroscopy 251
12.3 Characterisation of living cells 254
12.4 Characterisation of tissue engineering scaffolds 259
12.5 Conclusions and future trends 263
12.6 References 264

Part II Tissue and organ generation

13 Engineering of tissues and organs 269

A AT A L A , Wake Forest University, USA
13.1 Introduction 269
13.2 Native cells 270
13.3 Biomaterials 271
13.4 Alternate cell sources: stem cells and nuclear transfer 273
13.5 Tissue engineering of specific structures 277
13.6 Cellular therapies 284
13.6 Conclusions and future trends 288
13.7 References 289
 Contents ix

14 Bone regeneration and repair using tissue

engineering 294
P WO ZÂ N I A K , Medical University of Warsaw, Poland and
A J EL HA J , Keele University Medical School, UK
14.1 Introduction 294
14.2 Principles of bone biology 294
14.3 Basics of bone remodelling 299
14.4 Skeletal tissue reconstruction ± a tissue engineering approach 304
14.5 Conclusions 314
14.6 Acknowledgements 315
14.7 References 315

15 Bone tissue engineering and biomineralization 319

L DI SI L V I O , Kings College London, UK
15.1 Introduction 319
15.2 Tissue engineering 320
15.3 Scaffolds and biomineralization 327
15.4 Conclusions and future trends 330
15.5 References 331

16 Cardiac tissue engineering 335

Q Z CH E N , S E HA R D I N G , N N AL I , H JA W A D and
A R BO C C A C C I N I , Imperial College London, UK
16.1 Introduction 335
16.2 Cell sources 336
16.3 Construct-based strategies in myocardial tissue engineering 343
16.4 Conclusions and future trends 350
16.5 Acknowledgement 352
16.6 References and further reading 352

17 Intervertebral disc tissue engineering 357

J HO Y L A N D and T FR E E M O N T , University of Manchester,
UK
17.1 Introduction 357
17.2 The impact of disorders of the intervertebral disc (IVD) on
modern society 357
17.3 The normal anatomy, function and cell biology of the IVD 358
17.4 The pathobiology of IVD degeneration 359
17.5 Treatment of degeneration of the IVD 364
17.6 The place of biomaterials in proposed strategies for managing
IVD degeneration 366
17.7 Tissue regeneration and the IVD 371
x Contents

17.8 Conclusions 372

17.9 Future trends 373
17.10 Sources of further information and advice 374
17.11 References 375

18 Skin tissue engineering 379

S MA C NE I L , University of Sheffield, UK
18.1 Why do we need tissue-engineered skin? 379
18.2 Key events in the development of tissue-engineered skin 383
18.3 Do we need stem cells for tissue engineering of skin? 385
18.4 Key steps in development of tissue-engineered skin for
clinical use 385
18.5 Challenges in converting research into products 386
18.6 Clinical problems in the use of tissue-engineered skin 391
18.7 Unexpected results from using 3D skin models 396
18.8 Future trends 398
18.9 References 399

19 Liver tissue engineering 404

K SH A K E S H E F F , University of Nottingham, UK
19.1 Introduction 404
19.2 The structure of the liver lobule 405
19.3 Clinical and commercial applications of engineered liver tissue 405
19.4 Approaches to liver tissue engineering 407
19.5 Conclusions 415
19.6 Future trends 416
19.7 References 416

20 Kidney tissue engineering 421

A SA I T O , Tokai University, Japan
20.1 Introduction 421
20.2 Present status of kidney regeneration 421
20.3 Functional limitation of current haemodialysis as an artificial
kidney 423
20.4 System configuration for bioartificial kidneys 423
20.5 Past and current status of development of bioartificial kidneys 426
20.6 Attachment and proliferation of tubular epithelial cells on
polymer membranes 429
20.7 Function of tubular epithelial cells on polymer membranes 433
20.8 Evaluation of a long-term function of LLC-PK1 cell-attached
hollow fibre membrane 435
20.9 Improvement of the components of a portable bioartificial
kidney developed for long-term use 438
 Contents xi

20.10 Conclusions and future trends 441

20.11 References 442

21 Bladder tissue engineering 445

A M TU R N E R , University of York, UK, R SU B R A M A N I A M
and D F M TH O M A S , St. James's University Hospital, UK,
and J SO U T H G A T E , University of York, UK
21.1 The bladder ± structure and function 445
21.2 The clinical need for bladder reconstruction 447
21.3 Concepts and strategies of bladder reconstruction and tissue
engineering 448
21.4 Review of past and current strategies in bladder reconstruction 449
21.5 Cell conditioning in an external bioreactor 457
21.6 Future trends 458
21.7 Conclusions 459
21.8 References 459

22 Nerve bioengineering 466

P KI N G H A M and G TE R E N G H I , University of Manchester, UK
22.1 Peripheral nerve 466
22.2 Peripheral nerve injury and regeneration 468
22.3 Peripheral nerve repair 468
22.4 Bioengineered nerve conduits 469
22.5 Matrix materials 473
22.6 Cultured cells and nerve constructions 476
22.7 Conclusions 484
22.8 References 484

23 Lung tissue engineering 497

A E BI S H O P and H J RI P P O N , Imperial College London, UK
23.1 Introduction 497
23.2 Lung structure 497
23.3 Sources of cells for lung tissue engineering 499
23.4 Lung tissue constructs 501
23.5 Conclusions 505
23.6 References 505

24 Intestine tissue engineering 508

D A J LL O Y D and S M GA B E , St Mark's Hospital, UK
24.1 Introduction 508
24.2 Approaches to tissue engineering of the small intestine 508
24.3 Artificial scaffolds 510
xii Contents

24.4 Intestinal lengthening using artificial scaffolds 514

24.5 Transplantation of intestinal stem cell cultures 516
24.6 Growth factors 523
24.7 Future trends 524
24.8 Conclusions 525
24.9 References 525

25 Micromechanics of hydroxyapatite-based
biomaterials and tissue engineering scaffolds 529
A FR I T S C H and L DO R M I E U X , Ecole Nationale des Ponts
et ChausseÂes (LMSGC-ENPC), France, C HE L L M I C H , Vienna
University of Technology, Austria and J SA N A H U J A , Lafarge
Research Center, France
25.1 Introduction 529
25.2 Fundamentals of continuum micromechanics 535
25.3 Micromechanical representation of mono-porosity biomaterials
made of hydroxyapatite ± stiffness and strength estimates 538
25.4 Model validation 542
25.5 Continuum micromechanics model for `hierarchical'
hydroxyapatite biomaterials with two pore spaces used for
tissue engineering 551
25.6 Conclusions and future trends 557
25.7 Appendix: Homothetic (`cone-type') shape of failure criterion
for hydroxyapatite biomaterials ± Drucker±Prager approximation 558
25.8 Nomenclature 559
25.9 References 563

26 Cartilage tissue engineering 566

J E GO U G H , University of Manchester, UK
26.1 Introduction 566
26.2 Structure, cellularity and extracellular matrix 566
26.3 The need for cartilage repair 567
26.4 Current treatments including autologous chondrocyte
transplantation 568
26.5 Cell source 569
26.6 Materials 570
26.7 Growth factors and oxygen 576
26.8 Loading 579
26.9 Osteochondral defects 580
26.10 Conclusions and future trends 580
26.11 References 581

Index 587
 Contributor contact details

(* = main contact) S. M. Best

Department of Materials Science and
Metallurgy
Editors University of Cambridge
Aldo R. Boccaccini Pembroke Street
Department of Materials Cambridge CB2 3QZ
Imperial College London UK
Prince Consort Road E-mail: [email protected]
London SW7 2BP
UK Chapter 2
E-mail: [email protected] Guobao Wei and Peter X. Ma*
Department of Biologic and
Julie E. Gough Materials Sciences
Materials Science Centre Department of Biomedical
School of Materials Engineering
University of Manchester Macromolecular Science and
Grosvenor Street Engineering Center
Manchester M1 7HS The University of Michigan
UK Ann Arbor
E-mail: [email protected] Michigan 48109-1078
USA
Chapter 1 E-mail: [email protected]
J. Huang*
Department of Mechanical Chapter 3
Engineering J. R. Jones
University College London Department of Materials
Torrington Place Imperial College London
London WC1E 7JE South Kensington Campus
UK London SW7 2AZ
E-mail: [email protected] UK
E-mail: [email protected]
xiv Contributor contact details

Chapter 4 Chapter 8
S. K. Misra and A. R. Boccaccini* F. Davis and S. P. J. Higson*
Department of Materials Cranfield Health
Imperial College London Cranfield University
Prince Consort Road Barton Rd
London SW7 2BP Silsoe MK45 4DT
UK UK
E-mail: [email protected] E-mail: [email protected]
[email protected]
Chapter 5
J. Mansbridge Chapter 9
Tecellact LLC Andrew J. Urquhart and
1685 Calle Camille Morgan R. Alexander*
La Jolla School of Pharmacy
USA University of Nottingham
E-mail: [email protected] University Park
[email protected] Nottingham NG7 2RD
UK
Chapter 6 E-mail:
K. Shakesheff* and G. Tsourpas [email protected]
Division of Drug Delivery and Tissue
Engineering Chapter 10
School of Pharmacy A. M. Donald
University of Nottingham Department of Physics
Nottingham NG7 2RD Cavendish Laboratory
UK University of Cambridge
E-mail: JJ Thomson Avenue
[email protected] Cambridge CB3 0HE
UK
Chapter 7 E-mail: [email protected]
N. Tirelli* and F. Cellesi
School of Pharmacy Chapter 11
University of Manchester S. I. Anderson
Oxford Road Advanced Microscopy Unit
Manchester M13 9PL School of Biomedical Science
UK E Floor Medical School
E-mail: Queens Medical Centre
[email protected] Clifton Boulevard
[email protected] Nottingham NG7 2UH
UK
E-mail:
[email protected]
 Contributor contact details xv

Chapter 12 Chapter 15
I. Notingher L. Di Silvio
School of Physics and Astronomy Senior Lecturer in Biomaterials &
University of Nottingham Biomimetics
University Park King's College London Dental
Nottingham NG7 2RD Institute
UK Biomaterials Science
E-mail: Floor 17, Guy's Tower
[email protected] Guy's Campus
St Thomas' Street
Chapter 13 London SE1 9RT
A. Atala UK
Wake Forest Institute for E-mail: [email protected]
Regenerative Medicine
Wake Forest University Health Chapter 16
Sciences Q. Z. Chen, H. Jawad, A. R.
Medical Center Boulevard Boccaccini*
Winston-Salem Department of Materials
NC 27157 Imperial College London
USA Prince Consort Road
E-mail: [email protected] London SW7 2BP
UK
Chapter 14 E-mail: [email protected]
P. WozÂniak*
Department of Biophysics and S. E. Harding and N. N. Ali
Human Physiology National Heart and Lung Institute
Medical University of Warsaw Imperial College London
Ul. Chalubinskiego 5 Dovehouse Street
02-004 Warsaw London SW3 6LY
Poland UK
E-mail: [email protected]
[email protected] Chapter 17
J. Hoyland* and T. Freemont
A. J. El Haj Tissue Injury and Repair Group
Institute for Science & Technology School of Medicine
in Medicine Stopford Building
Keele University The University of Manchester
Thornburrow Drive Oxford Road
Hartshill Manchester M13 9PT
Stoke-on-Trent ST4 7QB UK
UK E-mail:
E-mail: [email protected] [email protected]
[email protected]
xvi Contributor contact details

Chapter 18 R. Subramaniam and

S. MacNeil D. F. M. Thomas
Tissue Engineering Group Department of Paediatric Urology
Kroto Research Institute St James's University Hospital
University of Sheffield North Leeds LS9 7TF
Campus UK
Broad Lane E-mail: Ramnath.Subramaniam
Sheffield S3 7HQ @leedsth.nhs.uk
UK [email protected]
E-mail: [email protected]
Chapter 22
Chapter 19 P. Kingham* and G. Terenghi
K. Shakesheff Blond McIndoe Laboratories
Division of Drug Delivery and Tissue Tissue Injury and Repair Group
Engineering 3.106 Stopford Building
School of Pharmacy The University of Manchester School
University of Nottingham of Medicine
Nottingham NG7 2RD Oxford Road
UK Manchester M13 9PT
E-mail: UK
[email protected] E-mail:
Chapter 20 [email protected]
A. Saito [email protected]
Division of Nephrology and
Metabolism Chapter 23
Department of Medicine A. E. Bishop* and H. J. Rippon
Tokai University School of Medicine Stem Cells & Regenerative Medicine
Bohseidai Section on Experimental Medicine &
Isehara Toxicology
Kanagawa 259-1193 Imperial College Faculty of Medicine
Japan Hammersmith Campus
E-mail: [email protected] Du Cane Road
London W12 ONN
Chapter 21 UK
A. M. Turner and J. Southgate* E-mail: [email protected]
Jack Birch Unit of Molecular [email protected]
Carcinogenesis
Department of Biology
University of York
York YO10 5YW
UK
E-mail: [email protected]
[email protected]
 Contributor contact details xvii

Chapter 24 J. Sanahuja
D. A. J. Lloyd* and S. M. Gabe Lafarge Research Center
St Mark's Hospital San-Quentin Fallavier
Northwick Park France
Harrow HA1 3UJ
UK Chapter 26
E-mail: [email protected] J. E. Gough
[email protected] Materials Science Centre
School of Materials
Chapter 25 University of Manchester
A. Fritsch and L. Dormieux Grosvenor Street
Laboratory for Materials and Manchester M1 7HS
Structures UK
Ecole Nationale des Ponts et E-mail: [email protected]
ChausseÂes (LMSGC-ENPC)
Marne-la-Vallee
France

C. Hellmich*
Vienna University of Technology
Karlsplatz 13/E 202
1040 Wien
Austria
E-mail:
[email protected]