M. G. Raucci and A. Gloria, R and De Santis and L. Ambrosio, Institute of Composite and Biomedical Materials, National Research Council of Italy, Italy and K. E. Tanner, University of Glasgow, UKB. Alcock, SwitzerlandM. Quaye and J. Harvey, Queen Alexandra Hospital, UKH.J. Wilke, Institute of Orthopaedic Research and Biomechanics, University of Ulm, Germany and A. Rohlmann, Julius Wolff Institute, Charité - Universitatsmedizin Berlin, GermanyJ. Noailly and D. Lacroix, Institute for Bioengineering of Catalonia, SpainV. Mohan and M. C. Gupta, University of California, Davis Medical Center, USAG. Logroscino and L. Proietti and E. Pola, Catholic University of Rome, ItalyA. Gloria and R. De Santis and L. Ambrosio, Institute of Composite and Biomedical Materials, National Research Council of ItalyItaly and K. E. Tanner, University of Glasgow, UKP. A. Revell, UCL Eastman Dental Institute, UKD. Baxter, Royal Army Medical Corps, UK and J. Yeh, The Royal London Hospital, UKK. E. Tanner, University of Glasgow, UKT. W. Bauer, The Cleveland Clinic, USAC. Persson and H. Engqvist, Uppsala University, SwedenS. E. Maclaine and A. J. Bennett, University of Glasgow, UKM. Niinomi, Tohoku University, JapanS. Miot and A. Marsano and I. Martin, University Hospital of Basel, SwitzerlandR. Tsaryk, University Medical Center of the Johannes Gutenberg University, Germany and M. Santin, University of Brighton, UK and and E. Dohle and R. E. Unger and C. J. Kirkpatrick, University Medical Center of the Johannes Gutenberg University, GermanyA. Gloria and T. Russo and R. De Santis and L. Ambrosio, Institute of Composite and Biomedical Materials, National Research Council of Italy, ItalyT. H. Smit and M. N. Helder, VU University Medical Centre, The Netherlands

Contributor contact details	p. xiii
1 Introduction to biomaterials for spinal surgery	p. 1
1.1 Introduction	p. 1
1.2 Total disc replacement	p. 3
1.3 Nucleus pulposus replacement	p. 5
1.4 Materials for spinal applications	p. 7
1.5 Conclusions	p. 28
1.6 References	p. 29
Part 1 Fundamentals of biomaterials for spinal surgery	p. 39
2 An overview of the challenges of bringing a medical device for the spine to the market	p. 41
2.1 Introduction	p. 41 I
2.2 Selection and sourcing of materials in medical device developments	p. 43
2.3 Biocompatibility testing	p. 50
2.4 Medical device regulation	p. 59
2.5 Conclusions	p. 73
2.6 Acknowledgement	p. 74
2.7 References	p. 74
3 Introduction to spinal pathologies and clinical problems of the spine	p. 78
3.1 Introduction	p. 78
3.2 Degenerative spine disease	p. 80
3.3 Spinal trauma	p. 88
3.4 Spinal deformity	p. 97
3.5 Malignancy	p. 105
3.6 Infection	p. 108
3.7 Conclusions	p. 109
3.8 References	p. 110
4 Forces on the spine	p. 114
4.1 Introduction	p. 114
4.2 In vivo measured components of spinal loads	p. 115
4.3 In vitro measured spinal load components	p. 126
4.4 Analytical models for spinal load estimation	p. 129
4.5 Recommendations for the simulations of loads for in vitro and numerical studies	p. 133
4.6 Conclusions	p. 137
4.7 References	p. 137
5 Finite element modelling of the spine	p. 144
5.1 Introduction	p. 144
5.2 Functional spine biomechanics and strength of numerical explorations	p. 144
5.3 Geometrical approximations in spine finite element modelling	p. 156
5.4 Numerical approximations: accuracy and computational cost	p. 166
5.5 Constitutive models for the spine tissues	p. 179
5.6 Simulating the mechanical loads on the spine	p. 201
5.7 Model verifications and interpretations: the validation concept and quantitative validation	p. 207
5.8 Future trends and conclusions: the virtual physiological spine	p. 218
5.9 References	p. 219
6 Osteobiologic agents in spine surgery	p. 233
6.1 Introduction	p. 233
6.2 Bone formation and healing	p. 234
6.3 Osteobiologics for spine fusion	p. 239
6.4 Bone growth factors	p. 245
6.5 Cellular biologies	p. 251
6.6 Conclusions	p. 256
6.7 References	p. 257
Part II Spinal fusion and intervertebral discs	p. 263
7 Spine fusion: cages, plates and bone substitutes	p. 265
7.1 Introduction	p. 265
7.2 Spine fusion: historical concerns and surgical skills	p. 266
7.3 Bone substitutes in spine fusion	p. 276
7.4 Bone growth factors	p. 284
7.5 Autologous bone marrow	p. 286
7.6 Future trends	p. 287
7.7 References	p. 288
8 Artificial intervertebral discs	p. 295
8.1 Introduction	p. 295
8.2 Structure and function of the intervertebral disc	p. 296
8.3 The artificial intervertebral disc: design and materials	p. 298
8.4 Fibre-reinforced composite materials: basic principles	p. 301
8.5 Composite biomimetic artificial intervertebral discs	p. 303
8.6 Future trends and conclusions	p. 309
8.7 References	p. 310
9 Biological response to artificial discs	p. 313
9.1 Introduction	p. 313
9.2 The healing response to intervertebral disc implants	p. 316
9.3 Infection as a cause of failure of implants	p. 322
9.4 Loosening and the reaction to the products of wear and corrosion	p. 324
9.5 Carcinogenicity and genotoxicity of metal implants	p. 346
9.6 Conclusions	p. 347
9.7 References	p. 348
Part III Vertebroplasty and scoliosis surgery	p. 363
10 The use of polymethyl methacrylate (PMMA) in neurosurgery	p. 365
10.1 Introduction: a history of polymethyl methacrylate(PMMA)	p. 365
10.2 Characteristics of polymethyl methacrylate (PMMA)	p. 366
10.3 Preparation of polymethyl methacrylate (PMMA) for use in clinical practice	p. 370
10.4 Clinical use of polymethyl methacrylate (PMMA) in neurosurgery	p. 376
10.5 Developments in polymethyl methacrylate (PMMA)	p. 380
10.6 Conclusions	p. 382
10.7 Sources of further information	p. 383
10.8 References	p. 383
11 Optimising the properties of injectable materials for vertebroplasty and kyphoplasty	p. 385
11.1 Introduction	p. 385
11.2 Polymethyl methacrylate (PMMA) based bone cements	p. 390
11.3 Calcium phosphate and calcium sulfate based bone cements	p. 396
11.4 Conclusions	p. 399
11.5 References	p. 399
12 Injectable calcium phosphates for vertebral augmentation	p. 404
12.1 Introduction	p. 404
12.2 Polymethyl methacrylate (PMMA)	p. 405
12.3 Calcium phosphate cements	p. 406
12.4 Conclusions	p. 410
12.5 References	p. 411
13 Composite injectable materials for vertebroplasty	p. 414
13.1 Introduction: a background on the use of composites in vertebroplasty	p. 414
13.2 Properties of composites for vertebroplasty	p. 416
13.3 Further development in composite injectable materials	p. 425
13.4 Conclusions	p. 428
13.5 References	p. 428
14 Scoliosis implants' surgical requirements	p. 432
14.1 Introduction	p. 432
14.2 Definition of scoliosis	p. 435
14.3 Management of scoliosis	p. 441
14.4 eneral principles for spinal fusion	p. 448
14.5 Outcomes in scoliosis surgery	p. 451
14.6 Future development of biomechanical implants	p. 455
14.7 Conclusions	p. 458
14.8 Sources of further information	p. 458
14.9 References	p. 458
15 Shape memory, superelastic and low Young's modulus alloys	p. 462
15.1 Introduction	p. 462
15.2 Fundamental characteristics of shape memory and superelastic alloys	p. 463
15.3 Low Young's modulus alloys	p. 479
15.4 Metals required for spinal surgery	p. 480
15.5 Conclusions	p. 486
15.6 Acknowledgements	p. 486
15.7 References	p. 486
Part IV Regenerative medicine in the spine	p. 491
16 Cell-based tissue engineering approaches for disc regeneration	p. 493
16.1 Introduction	p. 493
16.2 Rationale behind the use of cells	p. 494
16.3 Choice of cell type (not including mesenchymalstem cells)	p. 498
16.4 Current issues to be addressed	p. 500
16.5 Future trends and conclusions	p. 503
16.6 Sources of further information	p. 505
16.7 References	p. 506
17 Angiogenesis control in spine regeneration	p. 510
17.1 Introduction	p. 510
17.2 The role and the mechanisms of angiogenesis	p. 511
17.3 Physiological and pathological vascularisation of different intervertebral disc (IVD) histological compartments	p. 514
17.4 Strategies to promote angiogenesis in tissue regeneration	p. 517
17.5 Angiogenesis inhibition in intervertebral disc (IVD)	p. 522 regenera
17.6 Future trends	p. 528
17.7 Sources of further information	p. 529
17.8 Acknowledgements	p. 530
17.9 References	p. 530
18 Stem cells for disc regeneration536M. J. Loughran and J. A. Hunt, University of Liverpool, UK
18.1 Introduction	p. 536
18.2 Tissue engineering solutions for intervertebral disc (IVD) disease	p. 539
18.3 Mesenchymal stem cells (MSC) .and regeneration of the intervertebral disc (IVD)	p. 541
18.4 Regeneration of the annulus	p. 551
18.5 use of scaffolds with mesenchymal stem cells (MSC) for intervertebral disc (IVD) regeneration	p. 552
18.6 Future trends	p. 554
18.7 Conclusions	p. 556
18.8 References	p. 557
19 Nucleus regeneration	p. 563
19.1 Introduction	p. 563
19.2 The intervertebral disc: anatomy, structure and function	p. 565
19.3 Mechanics-biology interrelation	p. 566
19.4 Annulus, nucleus and entire intervertebraldisc: the tissue engineering approach	p. 567
19.5 Conclusions	p. 576
19.6 References	p. 576
20 In vivo models of regenerative medicine in the spine	p. 582
20.1 Introduction	p. 582
20.2 Selecting an animal model	p. 584
20.3 Intervertebral spinal fusion	p. 589
20.4 Degenerative disc disease	p. 592
20.5 Future trends and conclusions	p. 597
20.6 Acknowledgements	p. 598
20.7 References	p. 598
Index	p. 608