Advertisement

Advances in Tissue Engineering Approaches to Treatment of Intervertebral Disc Degeneration: Cells and Polymeric Scaffolds for Nucleus Pulposus Regeneration

  • Jeremy J. Mercuri
  • Dan T. SimionescuEmail author
Chapter
Part of the Advances in Polymer Science book series (POLYMER, volume 247)

Abstract

Synthetic polymers and biopolymers are extensively used within the field of tissue engineering. Some common examples of these materials include polylactic acid, polyglycolic acid, collagen, elastin, and various forms of polysaccharides. In terms of application, these materials are primarily used in the construction of scaffolds that aid in the local delivery of cells and growth factors, and in many cases fulfill a mechanical role in supporting physiologic loads that would otherwise be supported by a healthy tissue. In this review we will examine the development of scaffolds derived from biopolymers and their use with various cell types in the context of tissue engineering the nucleus pulposus of the intervertebral disc.

Keywords

Biomaterials Biopolymers Intervertebral disc Intervertebral disc degeneration Nucleus pulposus Tissue engineering 

References

  1. 1.
    An HS, Thonar EJ, Masuda K (2003) Biological repair of intervertebral disc. Spine 28(15 Suppl):S86–S92Google Scholar
  2. 2.
    Deyo RA, Nachemson A, Mirza SK (2004) Spinal-fusion surgery - the case for restraint. N Engl J Med 350(7):722–726Google Scholar
  3. 3.
    Frymoyer JW, Cats-Baril WL (1991) An overview of the incidences and costs of low back pain. Orthop Clin North Am 22(2):263–271Google Scholar
  4. 4.
    Masuda K, Lotz JC (2010) New challenges for intervertebral disc treatment using regenerative medicine. Tissue Eng Part B Rev 16(1):147–158Google Scholar
  5. 5.
    Miller JA, Schmatz C, Schultz AB (1988) Lumbar disc degeneration: correlation with age, sex, and spine level in 600 autopsy specimens. Spine (Phila Pa 1976) 13(2):173–178Google Scholar
  6. 6.
    Boden SD (1996) The use of radiographic imaging studies in the evaluation of patients who have degenerative disorders of the lumbar spine. J Bone Joint Surg Am 78(1):114–124Google Scholar
  7. 7.
    Videman T, Nurminen M (2004) The occurrence of anular tears and their relation to lifetime back pain history: a cadaveric study using barium sulfate discography. Spine 29(23):2668–2676Google Scholar
  8. 8.
    Pye SR et al (2004) Radiographic features of lumbar disc degeneration and self-reported back pain. J Rheumatol 31(4):753–758Google Scholar
  9. 9.
    McNally DS et al (1996) In vivo stress measurement can predict pain on discography. Spine 21(22):2580–2587Google Scholar
  10. 10.
    Schwarzer AC et al (1995) The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine 20(17):1878–1883Google Scholar
  11. 11.
    Raj PP (2008) Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract 8(1):18–44Google Scholar
  12. 12.
    Hardingham T (1998) Cartilage: aggrecan – link protein – hyaluronan aggregates. Available from http://www.glycoforum.gr.jp/science/hyaluronan/HA05/HA05E.html. Last accessed 25 July 2011
  13. 13.
    Middleditch A, Oliver J (2005) Functional anatomy of the spine, 2nd edn. Elsevier, New YorkGoogle Scholar
  14. 14.
    Roberts S et al (2006) Histology and pathology of the human intervertebral disc. J Bone Joint Surg Am 88(Suppl 2):10–14Google Scholar
  15. 15.
    Roberts S et al (1996) Transport properties of the human cartilage endplate in relation to its composition and calcification. Spine (Phila Pa 1976) 21(4):415–420Google Scholar
  16. 16.
    Roughley PJ (2004) Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 29(23):2691–2699Google Scholar
  17. 17.
    Eyre DR, Matsui Y, Wu JJ (2002) Collagen polymorphisms of the intervertebral disc. Biochem Soc Trans 30:844–848Google Scholar
  18. 18.
    Vaughan L et al (1988) D-periodic distribution of collagen type IX along cartilage fibrils. J Cell Biol 106(3):991–997Google Scholar
  19. 19.
    Eyre DR (1988) Collagens of the disc. In: Ghosh P (ed) The biology of the intervertebral disc. CRC, Boca Raton, pp 171–188Google Scholar
  20. 20.
    Urban JP (2000) The nucleus of the intervertebral disc from development to degeneration. Am Zool 40(1):53–61Google Scholar
  21. 21.
    Le Maitre CL et al (2007) Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem Soc Trans 35(Pt 4):652–655Google Scholar
  22. 22.
    Richardson SM et al (2007) Intervertebral disc biology, degeneration and novel tissue engineering and regenerative medicine therapies. Histol Histopathol 22(9):1033–1041Google Scholar
  23. 23.
    Mwale F, Roughley P, Antoniou J (2004) Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc. Eur Cell Mater 8:58–63Google Scholar
  24. 24.
    Horner HA et al (2002) Cells from different regions of the intervertebral disc: effect of culture system on matrix expression and cell phenotype. Spine (Phila Pa 1976) 27(10):1018–1028Google Scholar
  25. 25.
    Hunter CJ, Matyas JR, Duncan NA (2003) The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng 9(4):667–677Google Scholar
  26. 26.
    Roberts S et al (2000) Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc. Spine (Phila Pa 1976) 25(23):3005–3013Google Scholar
  27. 27.
    Rutges JP et al (2008) Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels. J Pathol 214(4):523–530Google Scholar
  28. 28.
    Urban JP, McMullin JF (1988) Swelling pressure of the lumbar intervertebral discs: influence of age, spinal level, composition, and degeneration. Spine 13(2):179–187Google Scholar
  29. 29.
    Sato K, Kikuchi S, Yonezawa T (1999) In vivo intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems. Spine 24(23):2468–2474Google Scholar
  30. 30.
    Wilke HJ et al (1999) New in vivo measurements of pressures in the intervertebral disc in daily life. Spine 24(8):755–762Google Scholar
  31. 31.
    Boos N et al (2002) Classification of age-related changes in lumbar intervertebral discs: 2002 volvo award in basic science. Spine (Phila Pa 1976), 27(23):2631–2644Google Scholar
  32. 32.
    Roughley PJ et al (2006) The structure and degradation of aggrecan in human intervertebral disc. Eur Spine J 15(Suppl 3):S326–S332Google Scholar
  33. 33.
    Walker MH, Anderson DG (2004) Molecular basis of intervertebral disc degeneration. Spine J 4(6 Suppl):158S–166SGoogle Scholar
  34. 34.
    Urban JP, Roberts S (2003) Degeneration of the intervertebral disc. Arthritis Res Ther 5(3):120–130Google Scholar
  35. 35.
    Antoniou J et al (1996) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 98(4):996–1003Google Scholar
  36. 36.
    Sztrolovics R et al (1997) Aggrecan degradation in human intervertebral disc and articular cartilage. Biochem J 326(Pt 1):235–241Google Scholar
  37. 37.
    Hollander AP et al (1996) Enhanced denaturation of the alpha (II) chains of type-II collagen in normal adult human intervertebral discs compared with femoral articular cartilage. J Orthop Res 14(1):61–66Google Scholar
  38. 38.
    Oegema TR Jr et al (2000) Fibronectin and its fragments increase with degeneration in the human intervertebral disc. Spine (Phila Pa 1976) 25(21):2742–2747Google Scholar
  39. 39.
    Yasuda T, Poole AR (2002) A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1-mediated pathway. Arthritis Rheum 46(1):138–148Google Scholar
  40. 40.
    Yasuda T et al (2006) Peptides of type II collagen can induce the cleavage of type II collagen and aggrecan in articular cartilage. Matrix Biol 25(7):419–429Google Scholar
  41. 41.
    Goupille P et al (1998) Matrix metalloproteinases: the clue to intervertebral disc degeneration? Spine (Phila Pa 1976) 23(14):1612–1626Google Scholar
  42. 42.
    Le Maitre CL, Freemont AJ, Hoyland JA (2004) Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 204(1):47–54Google Scholar
  43. 43.
    Zhao CQ et al (2007) The cell biology of intervertebral disc aging and degeneration. Ageing Res Rev 6(3):247–261Google Scholar
  44. 44.
    Iatridis JC et al (1997) Alterations in the mechanical behavior of the human lumbar nucleus pulposus with degeneration and aging. J Orthop Res 15(2):318–322Google Scholar
  45. 45.
    Johannessen W, Elliott DM (2005) Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine (Phila Pa 1976) 30(24):E724–E729Google Scholar
  46. 46.
    Goel VK et al (1995) Interlaminar shear stresses and laminae separation in a disc: finite element analysis of the L3-L4 motion segment subjected to axial compressive loads. Spine (Phila Pa 1976) 20(6):689–698Google Scholar
  47. 47.
    Niosi CA, Oxland TR (2004) Degenerative mechanics of the lumbar spine. Spine J 4(6 Suppl):202S–208SGoogle Scholar
  48. 48.
    Tsantrizos A et al (2005) Internal strains in healthy and degenerated lumbar intervertebral discs. Spine (Phila Pa 1976) 30(19):2129–2137Google Scholar
  49. 49.
    Perez-Cruet MJ, Khoo LT, Fessler RG (eds) (2006) An anatomical approach to minimally invasive spine surgery. Quality Medical Publishing, St. LouisGoogle Scholar
  50. 50.
    Bastian L et al (2001) Evaluation of the mobility of adjacent segments after posterior thoracolumbar fixation: a biomechanical study. Eur Spine J 10(4):295–300Google Scholar
  51. 51.
    Eck JC, Humphreys SC, Hodges SD (1999) Adjacent-segment degeneration after lumbar fusion: a review of clinical, biomechanical, and radiologic studies. Am J Orthop 28(6):336–340Google Scholar
  52. 52.
    Putzier M et al (2006) Charite total disc replacement–clinical and radiographical results after an average follow-up of 17 years. Eur Spine J 15(2):183–195Google Scholar
  53. 53.
    van Ooij A et al (2007) Polyethylene wear debris and long-term clinical failure of the charite disc prosthesis: a study of 4 patients. Spine 32(2):223–229Google Scholar
  54. 54.
    van Ooij A, Oner FC, Verbout AJ (2003) Complications of artificial disc replacement: a report of 27 patients with the SB charite disc. J Spinal Disord Tech 16(4):369–383Google Scholar
  55. 55.
    Zeh A et al (2007) Release of cobalt and chromium ions into the serum following implantation of the metal-on-metal Maverick-type artificial lumbar disc (Medtronic Sofamor Danek). Spine 32(3):348–352Google Scholar
  56. 56.
    Girardi FP, Viscogliosi Bros (2007) Worldwide orthopedic and spine market. In: Davis RJ, Girardi FP (eds) Nucleus arthroplasty technology in spinal care, vol 1. Raymedica, Minneapolis, pp 21–26. Available at http://www.thesona.com/sona2.swf. Last accessed 25 July 2011
  57. 57.
    Ahrens M, Tsantrizos A, LeHuec J (2008) DASCOR. In: Yue J, Bertagnoli R, McAfee P, An H (eds) Motion preservation surgery of the spine; advanced techniques and controversies. Elsevier, Philadelphia, pp 397–407Google Scholar
  58. 58.
    Yue J, Bertagnoli R, McAfee P, An H (2008) Motion preservation surgery of the spine; advanced techniques and controversies. Elsevier, Philadelphia, pp 397–465Google Scholar
  59. 59.
    Ahrens M et al (2009) Nucleus replacement with the DASCOR disc arthroplasty device: interim two-year efficacy and safety results from two prospective, non-randomized multicenter European studies. Spine (Phila Pa 1976) 34(13):1376–1384Google Scholar
  60. 60.
    Vernengo J et al (2008) Evaluation of novel injectable hydrogels for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater 84(1):64–69Google Scholar
  61. 61.
    Boyd LM, Carter AJ (2006) Injectable biomaterials and vertebral endplate treatment for repair and regeneration of the intervertebral disc. Eur Spine J 15(Suppl 3):S414–S421Google Scholar
  62. 62.
    Wardlaw D (2008) BioDisc nucleus pulposus replacement. In: Yue J, Bertagnoli R, McAfee P, An H (eds) Motion preservation surgery of the spine: advanced techniques and controversies. Elsevier, Philadelphia, pp 431–441Google Scholar
  63. 63.
    Bertagnoli R, Schonmayr R (2002) Surgical and clinical results with the PDN prosthetic disc-nucleus device. Eur Spine J 11(Suppl 2):S143–S148Google Scholar
  64. 64.
    Bertagnoli R et al (2005) Mechanical testing of a novel hydrogel nucleus replacement implant. Spine J 5(6):672–681Google Scholar
  65. 65.
    Joshi A et al (2006) Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials 27(2):176–184Google Scholar
  66. 66.
    Thomas J et al (2004) The effect of dehydration history on PVA/PVP hydrogels for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater 69(2):135–140Google Scholar
  67. 67.
    Thomas J, Lowman A, Marcolongo M (2003) Novel associated hydrogels for nucleus pulposus replacement. J Biomed Mater Res A 67(4):1329–1337Google Scholar
  68. 68.
    Bao QB, Bagga CS, Higham PA (1997) Swelling pressure of hydrogel: a perceived benefit for a spinal prosthetic nucleus. In: Proceedings 10th annual meeting of the International Intradiscal Therapy Society, Naples, FLGoogle Scholar
  69. 69.
    Boelen EJ et al (2005) Intrinsically radiopaque hydrogels for nucleus pulposus replacement. Biomaterials 26(33):6674–6683Google Scholar
  70. 70.
    Lau S, Lam K (2007) Lumbar stabilisation techniques. Curr Orthop 21:25–39Google Scholar
  71. 71.
    Laurencin CT et al (1999) Tissue engineering: orthopedic applications. Annu Rev Biomed Eng 1:19–46Google Scholar
  72. 72.
    Nerem RM, Sambanis A (1995) Tissue engineering: from biology to biological substitutes. Tissue Eng 1(1):3–13Google Scholar
  73. 73.
    Halloran DO et al (2008) An injectable cross-linked scaffold for nucleus pulposus regeneration. Biomaterials 29(4):438–447Google Scholar
  74. 74.
    Richardson SM et al (2008) Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels. Biomaterials 29(1):85–93Google Scholar
  75. 75.
    Chan S, Lam S, Leung V, Chan D, Luk K, Cheung K (2010) Minimizing cryopreservation-induced loss of disc cell activity for storage of whole intervertebral discs. Eur Cells Mater 19:273–283Google Scholar
  76. 76.
    Ganey T et al (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine (Phila Pa 1976) 28(23):2609–2620Google Scholar
  77. 77.
    Gorensek M et al (2004) Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol Biol Lett 9(2):363–373Google Scholar
  78. 78.
    Bae H, Kanim M, Zhao L (2008) Human fetal chondrocyte transplants for damaged intervertebral disc. Spine J 8(5):928–938Google Scholar
  79. 79.
    Kaneyama S et al (2008) Fas ligand expression on human nucleus pulposus cells decreases with disc degeneration processes. J Orthop Sci 13(2):130–135Google Scholar
  80. 80.
    Takada T et al (2002) Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc. Spine (Phila Pa 1976) 27(14):1526–1530Google Scholar
  81. 81.
    Wolfe HJ, Putschar WG, Vickery AL (1965) Role of the notochord in human intervetebral disk. I. Fetus and infant. Clin Orthop Relat Res 39:205–212Google Scholar
  82. 82.
    Cappello R et al (2006) Notochordal cell produce and assemble extracellular matrix in a distinct manner, which may be responsible for the maintenance of healthy nucleus pulposus. Spine (Phila Pa 1976) 31(8):873–882, discussion 883Google Scholar
  83. 83.
    Erwin WM et al (2006) Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes. Arthritis Rheum 54(12):3859–3867Google Scholar
  84. 84.
    Erwin WM et al (2009) The regenerative capacity of the notochordal cell: tissue constructs generated in vitro under hypoxic conditions. J Neurosurg Spine 10(6):513–521Google Scholar
  85. 85.
    Aguiar DJ, Johnson SL, Oegema TR (1999) Notochordal cells interact with nucleus pulposus cells: regulation of proteoglycan synthesis. Exp Cell Res 246(1):129–137Google Scholar
  86. 86.
    Korecki CL et al (2010) Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype. Stem Cell Res Ther 1(2):18Google Scholar
  87. 87.
    Mercuri J, Gill S, Simionescu A, Simionescu D (2010) Xenogenic cues for human mesenchymal stem cell differentiation towads a nucleus pulposus cell-like phenotype. In: Proceedings 25th Annual Meeting of the North American Spine Society. Spine J 10(9):S114–S115Google Scholar
  88. 88.
    Pittenger MF et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147Google Scholar
  89. 89.
    Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822Google Scholar
  90. 90.
    McIntosh KR et al (2009) Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Eng Part A 15(9):2677–2686Google Scholar
  91. 91.
    Steck E et al (2005) Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 23(3):403–411Google Scholar
  92. 92.
    Risbud M, Izzo M, Adams C et al. (2003) Mesenchymal stem cells respond to their microenvironment and in vitro to assume nucleus pulposus-like phenotype. Paper presented at 30th Annual Meeting of the International Society for the Study of the Lumbar Spine. Vancouver, CanadaGoogle Scholar
  93. 93.
    Richardson SM et al (2006) Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells 24(3):707–716Google Scholar
  94. 94.
    Sobajima S et al (2008) Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 8(6):888–896Google Scholar
  95. 95.
    Sakai D et al (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27(3):335–345Google Scholar
  96. 96.
    Li X et al (2005) Modulation of chondrocytic properties of fat-derived mesenchymal cells in co-cultures with nucleus pulposus. Connect Tissue Res 46(2):75–82Google Scholar
  97. 97.
    Lu ZF et al (2007) Differentiation of adipose stem cells by nucleus pulposus cells: configuration effect. Biochem Biophys Res Commun 359(4):991–996Google Scholar
  98. 98.
    Kluba T et al (2005) Human anulus fibrosis and nucleus pulposus cells of the intervertebral disc: effect of degeneration and culture system on cell phenotype. Spine (Phila Pa 1976) 30(24):2743–2748Google Scholar
  99. 99.
    Stokes DG et al (2001) Regulation of type-II collagen gene expression during human chondrocyte de-differentiation and recovery of chondrocyte-specific phenotype in culture involves Sry-type high-mobility-group box (SOX) transcription factors. Biochem J 360(Pt 2):461–470Google Scholar
  100. 100.
    Tsai TT et al (2007) Fibroblast growth factor-2 maintains the differentiation potential of nucleus pulposus cells in vitro: implications for cell-based transplantation therapy. Spine (Phila Pa 1976) 32(5):495–502Google Scholar
  101. 101.
    Yang SH et al (2005) An in-vitro study on regeneration of human nucleus pulposus by using gelatin/chondroitin-6-sulfate/hyaluronan tri-copolymer scaffold. Artif Organs 29(10):806–814Google Scholar
  102. 102.
    Yang SH et al (2005) Gelatin/chondroitin-6-sulfate copolymer scaffold for culturing human nucleus pulposus cells in vitro with production of extracellular matrix. J Biomed Mater Res B Appl Biomater 74(1):488–494Google Scholar
  103. 103.
    Li CQ et al (2009) Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering and preliminary analysis of its physico-chemical properties and biocompatibility. J Mater Sci Mater Med 21:741–751Google Scholar
  104. 104.
    Calderon L et al (2010) Type II collagen-hyaluronan hydrogel–a step towards a scaffold for intervertebral disc tissue engineering. Eur Cell Mater 20:134–148Google Scholar
  105. 105.
    Sakai D et al (2006) Atelocollagen for culture of human nucleus pulposus cells forming nucleus pulposus-like tissue in vitro: influence on the proliferation and proteoglycan production of HNPSV-1 cells. Biomaterials 27(3):346–353Google Scholar
  106. 106.
    Yu J (2002) Elastic tissues of the intervertebral disc. Biochem Soc Trans 30(Pt 6):848–852Google Scholar
  107. 107.
    Chuang TH et al (2009) Polyphenol-stabilized tubular elastin scaffolds for tissue engineered vascular grafts. Tissue Eng Part A 15(10):2837–2851Google Scholar
  108. 108.
    Tedder ME et al (2009) Stabilized collagen scaffolds for heart valve tissue engineering. Tissue Eng Part A 15(6):1257–1268Google Scholar
  109. 109.
    Addington C, Mercuri J, Gill S, Simionescu D (2011) Stabilized elastin-glycosaminoglycan shape-memory sponge scaffold for nucleus pulposus tissue engineering. In: Transactions 2011 Orthopaedic Research Society Annual Meeting. Long Beach, CAGoogle Scholar
  110. 110.
    Daamen WF et al (2003) Preparation and evaluation of molecularly-defined collagen-elastin-glycosaminoglycan scaffolds for tissue engineering. Biomaterials 24(22):4001–4009Google Scholar
  111. 111.
    Badylak SF (2007) The extracellular matrix as a biologic scaffold material. Biomaterials 28(25):3587–3593Google Scholar
  112. 112.
    Wu Z et al (2009) The use of phospholipase A(2) to prepare acellular porcine corneal stroma as a tissue engineering scaffold. Biomaterials 30(21):3513–3522Google Scholar
  113. 113.
    Mercuri J, Gill S, Simionescu D (2011) Novel tissue derived biomimetic scaffold for regenerating the human nucleus pulposus. J Biomed Mater Res A 96(2):422–435Google Scholar
  114. 114.
    Cloyd JM et al (2007) Material properties in unconfined compression of human nucleus pulposus, injectable hyaluronic acid-based hydrogels and tissue engineering scaffolds. Eur Spine J 16(11):1892–1898Google Scholar
  115. 115.
    Seguin CA et al (2004) Tissue engineered nucleus pulposus tissue formed on a porous calcium polyphosphate substrate. Spine (Phila Pa 1976) 29(12):1299–1306Google Scholar
  116. 116.
    Le Visage C et al (2006) Small intestinal submucosa as a potential bioscaffold for intervertebral disc regeneration. Spine 31(21):2423–2430, discussion 2431Google Scholar
  117. 117.
    Baer AE et al (2001) Collagen gene expression and mechanical properties of intervertebral disc cell-alginate cultures. J Orthop Res 19(1):2–10Google Scholar
  118. 118.
    Chou AI, Nicoll SB (2009) Characterization of photocrosslinked alginate hydrogels for nucleus pulposus cell encapsulation. J Biomed Mater Res A 91(1):187–194Google Scholar
  119. 119.
    Chou AI, Akintoye SO, Nicoll SB (2009) Photo-crosslinked alginate hydrogels support enhanced matrix accumulation by nucleus pulposus cells in vivo. Osteoarthr Cartil 17(10):1377–1384Google Scholar
  120. 120.
    Leone G et al (2008) Amidic alginate hydrogel for nucleus pulposus replacement. J Biomed Mater Res A 84(2):391–401Google Scholar
  121. 121.
    Gaetani P et al (2008) Adipose-derived stem cell therapy for intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules. Tissue Eng Part A 14(8):1415–1423Google Scholar
  122. 122.
    Roughley P et al (2006) The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation. Biomaterials 27(3):388–396Google Scholar
  123. 123.
    Reza AT, Nicoll SB (2009) Characterization of novel photocrosslinked carboxymethylcellulose hydrogels for encapsulation of nucleus pulposus cells. Acta Biomater 6(1):179–186Google Scholar
  124. 124.
    Yang SH et al (2008) Three-dimensional culture of human nucleus pulposus cells in fibrin clot: comparisons on cellular proliferation and matrix synthesis with cells in alginate. Artif Organs 32(1):70–73Google Scholar
  125. 125.
    Hamilton DJ et al (2006) Formation of a nucleus pulposus-cartilage endplate construct in vitro. Biomaterials 27(3):397–405Google Scholar
  126. 126.
    Brown RQ, Mount A, Burg KJ (2005) Evaluation of polymer scaffolds to be used in a composite injectable system for intervertebral disc tissue engineering. J Biomed Mater Res A 74(1):32–39Google Scholar
  127. 127.
    Abbushi A et al (2008) Regeneration of intervertebral disc tissue by resorbable cell-free polyglycolic acid-based implants in a rabbit model of disc degeneration. Spine 33(14):1527–1532Google Scholar
  128. 128.
    Revell PA et al (2007) Tissue engineered intervertebral disc repair in the pig using injectable polymers. J Mater Sci Mater Med 18(2):303–308Google Scholar
  129. 129.
    Nomura T et al (2001) Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop Relat Res 389:94–101Google Scholar
  130. 130.
    Alini M et al (2008) Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 17(1):2–19Google Scholar
  131. 131.
    O’Connell GD, Vresilovic EJ, Elliott DM (2007) Comparison of animals used in disc research to human lumbar disc geometry. Spine (Phila Pa 1976) 32(3):328–333Google Scholar
  132. 132.
    Gillett NA et al (1988) Age-related changes in the beagle spine. Acta Orthop Scand 59(5):503–507Google Scholar
  133. 133.
    Nuckley DJ et al (2008) Intervertebral disc degeneration in a naturally occurring primate model: radiographic and biomechanical evidence. J Orthop Res 26(9):1283–1288Google Scholar
  134. 134.
    Ziv I et al (1992) Physicochemical properties of the aging and diabetic sand rat intervertebral disc. J Orthop Res 10(2):205–210Google Scholar
  135. 135.
    Masuda K et al (2005) A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 30(1):5–14Google Scholar
  136. 136.
    Sobajima S et al (2005) A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine 30(1):15–24Google Scholar
  137. 137.
    Singh K, Masuda K, An H (2008) Animal models for human disc degeneration. In: Yue J, Bertagnoli R, McAfee P, An H (eds) Motion preservation surgery of the spine: advanced techniques and controversies. Elsevier, Philadelphia, pp 639–648Google Scholar
  138. 138.
    Ulrich JA et al (2007) ISSLS prize winner: repeated disc injury causes persistent inflammation. Spine 32(25):2812–2819Google Scholar
  139. 139.
    Iatridis JC et al (1999) Compression-induced changes in intervertebral disc properties in a rat tail model. Spine (Phila Pa 1976) 24(10):996–1002Google Scholar
  140. 140.
    Kroeber MW et al (2002) New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine (Phila Pa 1976) 27(23):2684–2690Google Scholar
  141. 141.
    Kim KS et al (2005) Disc degeneration in the rabbit: a biochemical and radiological comparison between four disc injury models. Spine (Phila Pa 1976) 30(1):33–37Google Scholar
  142. 142.
    Hoogendoorn RJ et al (2007) Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat. Spine (Phila Pa 1976) 32(17):1816–1825Google Scholar
  143. 143.
    Zhou H et al (2007) A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology. Spine (Phila Pa 1976) 32(8):864–872Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of BioengineeringClemson UniversityClemsonUSA
  2. 2.Department of BioengineeringClemson UniversityClemsonUSA

Personalised recommendations