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The challenge and advancement of annulus fibrosus tissue engineering

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Abstract

Background

Intervertebral disc degeneration, a main cause of back pain, is an endemic problem and a big economic burden for the health care system. Current treatments are symptom relieving but do not address underlying problems—biological and structural deterioration of the disc. Tissue engineering is an emerging approach for the treatment of intervertebral disc degeneration since it restores the functionality of native tissues. Although numerous studies have focused on the nucleus pulposus tissue engineering and achieved successes in laboratory settings, disc tissue engineering without annulus fibrosus for the end stage of disc degeneration is deemed to fail. The purpose of this article is to review the advancement of annulus fibrosus tissue engineering.

Material and Methods

Relevant articles regarding annulus fibrosus tissue engineering were identified in PubMed and Medline databases.

Results

The ideal strategy for disc regeneration is to restore the function and integrity of the disc by using biomaterials, native matrices, growth factors, and cells that producing matrices. In the past decades there are tremendous advancement in annulus fibrosus tissue engineering including cell biology, biomaterials, and whole disc replacement. The recent promising results on whole disc tissue engineering—a composite of annulus fibrosus and nucleus pulposus—make the tissue engineering approach more appealing.

Conclusion

Despite the promising results in disc tissue engineering, there is still much work to be done regarding the clinical application.

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References

  1. Freemont TJ, LeMaitre C, Watkins A, Hoyland JA (2001) Degeneration of intervertebral discs: current understanding of cellular and molecular events, and implications for novel therapies. Expert Rev Mol Med 2001:1–10

    PubMed  Google Scholar 

  2. Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P (2000) Mechanical initiation of intervertebral disc degeneration. Spine (Phila Pa 1976) 25:1625–1636

    Article  CAS  Google Scholar 

  3. Mannion AF, Adams MA, Dolan P (2000) Sudden and unexpected loading generates high forces on the lumbar spine. Spine (Phila Pa 1976) 25:842–852

    Article  CAS  Google Scholar 

  4. Horner HA, Urban JP (2001) Volvo award winner in basic science studies: effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine (Phila Pa 1976) 26:2543–2549

    Article  CAS  Google Scholar 

  5. Brown MD, Malinin TI, Davis PB (1976) A roentgenographic evaluation of frozen allografts versus autografts in anterior cervical spine fusions. Clin Orthop Relat Res 119:231–236

    PubMed  Google Scholar 

  6. Bibby SR, Urban JP (2004) Effect of nutrient deprivation on the viability of intervertebral disc cells. Eur Spine J 13:695–701

    Article  PubMed  CAS  Google Scholar 

  7. Yang X, Li X (2009) Nucleus pulposus tissue engineering: a brief review. Eur Spine J 18:1564–1572

    Article  PubMed  Google Scholar 

  8. Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 20:1307–1314

    CAS  Google Scholar 

  9. Haefeli M, Elfering A, Kilian R, Min K, Boos N (2006) Nonoperative treatment for adolescent idiopathic scoliosis: A 10- to 60-year follow-up with special reference to health-related quality of life. Spine (Phila Pa 1976) 31:355–366 discussion 367

    Article  Google Scholar 

  10. Anderson DG, Tannoury C (2005) Molecular pathogenic factors in symptomatic disc degeneration. Spine J 5:260S–266S

    Article  PubMed  Google Scholar 

  11. Anderson DG, Albert TJ, Fraser JK, Risbud M, Wuisman P, Meisel HJ, Tannoury C, Shapiro I, Vaccaro AR (2005) Cellular therapy for disc degeneration. Spine (Phila Pa 1976) 30:S14–S19

    Article  Google Scholar 

  12. Kurtz SM, Devine JN (2007) PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials 28:4845–4869

    Article  PubMed  CAS  Google Scholar 

  13. Kurtz SM, Ong KL, Schmier J, Mowat F, Saleh K, Dybvik E, Karrholm J, Garellick G, Havelin LI, Furnes O, Malchau H, Lau E (2007) Future clinical and economic impact of revision total hip and knee arthroplasty. J Bone Joint Surg Am 89(Suppl 3):144–151

    Article  PubMed  Google Scholar 

  14. Kurtz SM, van Ooij A, Ross R, de Waal Malefijt J, Peloza J, Ciccarelli L, Villarraga ML (2007) Polyethylene wear and rim fracture in total disc arthroplasty. Spine J 7:12–21

    Article  PubMed  Google Scholar 

  15. Punt IM, Visser VM, van Rhijn LW, Kurtz SM, Antonis J, Schurink GW, van Ooij A (2008) Complications and reoperations of the SB charite lumbar disc prosthesis: experience in 75 patients. Eur Spine J 17:36–43

    Article  PubMed  Google Scholar 

  16. Serhan HA, Dooris AP, Parsons ML, Ares PJ, Gabriel SM (2006) In vitro wear assessment of the charite artificial disc according to ASTM recommendations. Spine (Phila Pa 1976) 31:1900–1910

    Article  Google Scholar 

  17. Slivka MA, Spenciner DB, Seim HB 3rd, Welch WC, Serhan HA, Turner AS (2006) High rate of fusion in sheep cervical spines following anterior interbody surgery with absorbable and nonabsorbable implant devices. Spine (Phila Pa 1976) 31:2772–2777

    Article  Google Scholar 

  18. Lyons G, Eisenstein SM, Sweet MB (1981) Biochemical changes in intervertebral disc degeneration. Biochim Biophys Acta 673:443–453

    Article  PubMed  CAS  Google Scholar 

  19. An HS, Masuda K, Cs-Szabo G, Zhang Y, Chee A, Andersson GB, Im HJ, Thonar EJ, Kwon YM (2011) Biologic repair and regeneration of the intervertebral disk. J Am Acad Orthop Surg 19:450–452

    PubMed  Google Scholar 

  20. Cs-Szabo G, Ragasa-San Juan D, Turumella V, Masuda K, Thonar EJ, An HS (2002) Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during intervertebral disc degeneration. Spine (Phila Pa 1976) 27:2212–2219

    Article  Google Scholar 

  21. O’Halloran DM, Pandit AS (2007) Tissue-engineering approach to regenerating the intervertebral disc. Tissue Eng 13:1927–1954

    Article  PubMed  Google Scholar 

  22. Chan SC, Gantenbein-Ritter B (2012) Intervertebral disc regeneration or repair with biomaterials and stem cell therapy–feasible or fiction? Swiss Med Wkly 142:w13598

    PubMed  Google Scholar 

  23. Alini M, Roughley PJ, Antoniou J, Stoll T, Aebi M (2002) A biological approach to treating disc degeneration: not for today, but maybe for tomorrow. Eur Spine J 11(Suppl 2):S215–S220

    PubMed  Google Scholar 

  24. Nesti LJ, Li WJ, Shanti RM, Jiang YJ, Jackson W, Freedman BA, Kuklo TR, Giuliani JR, Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng Part A 14:1527–1537

    Article  PubMed  CAS  Google Scholar 

  25. Woiciechowsky C, Abbushi A, Zenclussen ML, Casalis P, Kruger JP, Freymann U, Endres M, Kaps C (2012) Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds. J Tissue Eng Regen Med [Epub ahead of print]

  26. Pei M, Shoukry M, Li J, Daffner SD, France JC, Emery SE (2012) Modulation of in vitro microenvironment facilitates synovium-derived stem cell-based nucleus pulposus tissue regeneration. Spine (Phila Pa 1976) 37:1538–1547

    Article  Google Scholar 

  27. Gupta MS, Cooper ES, Nicoll SB (2011) Transforming growth factor-beta 3 stimulates cartilage matrix elaboration by human marrow-derived stromal cells encapsulated in photocrosslinked carboxymethylcellulose hydrogels: potential for nucleus pulposus replacement. Tissue Eng Part A 17:2903–2910

    Article  PubMed  CAS  Google Scholar 

  28. Collin EC, Grad S, Zeugolis DI, Vinatier CS, Clouet JR, Guicheux JJ, Weiss P, Alini M, Pandit AS (2011) An injectable vehicle for nucleus pulposus cell-based therapy. Biomaterials 32:2862–2870

    Article  PubMed  CAS  Google Scholar 

  29. Mortisen D, Peroglio M, Alini M, Eglin D (2010) Tailoring thermoreversible hyaluronan hydrogels by “click” chemistry and RAFT polymerization for cell and drug therapy. Biomacromolecules 11:1261–1272

    Article  PubMed  CAS  Google Scholar 

  30. Peroglio M, Grad S, Mortisen D, Sprecher CM, Illien-Junger S, Alini M, Eglin D (2012) Injectable thermoreversible hyaluronan-based hydrogels for nucleus pulposus cell encapsulation. Eur Spine J 21(Suppl 6):S839–S849

    Article  PubMed  Google Scholar 

  31. Bowles RD, Gebhard HH, Hartl R, Bonassar LJ (2011) Tissue-engineered intervertebral discs produce new matrix, maintain disc height, and restore biomechanical function to the rodent spine. Proc Natl Acad Sci USA 108:13106–13111

    Article  PubMed  CAS  Google Scholar 

  32. Lazebnik M, Singh M, Glatt P, Friis LA, Berkland CJ, Detamore MS (2011) Biomimetic method for combining the nucleus pulposus and annulus fibrosus for intervertebral disc tissue engineering. J Tissue Eng Regen Med 5:e179–e187

    Article  PubMed  CAS  Google Scholar 

  33. Schollmeier G, Lahr-Eigen R, Lewandrowski KU (2000) Observations on fiber-forming collagens in the anulus fibrosus. Spine (Phila Pa 1976) 25:2736–2741

    Article  CAS  Google Scholar 

  34. Yu J, Tirlapur U, Fairbank J, Handford P, Roberts S, Winlove CP, Cui Z, Urban J (2007) Microfibrils, elastin fibres and collagen fibres in the human intervertebral disc and bovine tail disc. J Anat 210:460–471

    Article  PubMed  Google Scholar 

  35. Adams P, Eyre DR, Muir H (1977) Biochemical aspects of development and ageing of human lumbar intervertebral discs. Rheumatol Rehabil 16:22–29

    Article  PubMed  CAS  Google Scholar 

  36. Hayes AJ, Benjamin M, Ralphs JR (2001) Extracellular matrix in development of the intervertebral disc. Matrix Biol 20:107–121

    Article  PubMed  CAS  Google Scholar 

  37. Hayes AJ, Smith SM, Gibson MA, Melrose J (2011) Comparative immunolocalisation of the elastin fibre associated proteins fibrillin-1, LTBP2 and MAGP-1 with components of the collagenous and proteoglycan matrix of the foetal human IVD. Spine (Phila Pa 1976) 36(21):E1365–E1372

    Article  Google Scholar 

  38. Eyre DR, Muir H (1976) Types I and II collagens in intervertebral disc. interchanging radial distributions in annulus fibrosus. Biochem J 157:267–270

    PubMed  CAS  Google Scholar 

  39. Rufai A, Benjamin M, Ralphs JR (1995) The development of fibrocartilage in the rat intervertebral disc. Anat Embryol (Berl) 192:53–62

    Article  CAS  Google Scholar 

  40. Hayes AJ, Isaacs MD, Hughes C, Caterson B, Ralphs JR (2011) Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc. Eur Cell Mater 22:226–241

    PubMed  CAS  Google Scholar 

  41. Singh K, Masuda K, Thonar EJ, An HS, Cs-Szabo G (2009) Age-related changes in the extracellular matrix of nucleus pulposus and anulus fibrosus of human intervertebral disc. Spine (Phila Pa 1976) 34:10–16

    Article  Google Scholar 

  42. Pattappa G, Li Z, Peroglio M, Wismer N, Alini M, Grad S (2012) Diversity of intervertebral disc cells: phenotype and function. J Anat 221(6):480–496

    Article  PubMed  CAS  Google Scholar 

  43. Bruehlmann SB, Rattner JB, Matyas JR, Duncan NA (2002) Regional variations in the cellular matrix of the annulus fibrosus of the intervertebral disc. J Anat 201:159–171

    Article  PubMed  Google Scholar 

  44. Errington RJ, Puustjarvi K, White IR, Roberts S, Urban JP (1998) Characterisation of cytoplasm-filled processes in cells of the intervertebral disc. J Anat 192(Pt 3):369–378

    Article  PubMed  Google Scholar 

  45. Roughley P, Hoemann C, DesRosiers E, Mwale F, Antoniou J, Alini M (2006) The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation. Biomaterials 27:388–396

    Article  PubMed  CAS  Google Scholar 

  46. Clouet J, Grimandi G, Pot-Vaucel M, Masson M, Fellah HB, Guigand L, Cherel Y, Bord E, Rannou F, Weiss P, Guicheux J, Vinatier C (2009) Identification of phenotypic discriminating markers for intervertebral disc cells and articular chondrocytes. Rheumatology (Oxford) 48:1447–1450

    Article  CAS  Google Scholar 

  47. Minogue BM, Richardson SM, Zeef LA, Freemont AJ, Hoyland JA (2010) Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes. Arthritis Res Ther 12:R22

    Article  PubMed  CAS  Google Scholar 

  48. Gruber HE, Hoelscher GL, Hanley EN Jr (2010) Annulus cells from more degenerated human discs show modified gene expression in 3D culture compared with expression in cells from healthier discs. Spine J 10:721–727

    Article  PubMed  Google Scholar 

  49. Feng G, Yang X, Shang H, Marks IW, Shen FH, Katz A, Arlet V, Laurencin CT, Li X (2010) Multipotential differentiation of human anulus fibrosus cells: an in vitro study. J Bone Joint Surg Am 92:675–685

    Article  PubMed  Google Scholar 

  50. Risbud MV, Guttapalli A, Tsai TT, Lee JY, Danielson KG, Vaccaro AR, Albert TJ, Gazit Z, Gazit D, Shapiro IM (2007) Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine (Phila Pa 1976) 32:2537–2544

    Article  Google Scholar 

  51. Poiraudeau S, Monteiro I, Anract P, Blanchard O, Revel M, Corvol MT (1999) Phenotypic characteristics of rabbit intervertebral disc cells. Comparison with cartilage cells from the same animals. Spine (Phila Pa 1976) 24:837–844

    Article  CAS  Google Scholar 

  52. Gruber HE, Fisher EC Jr, Desai B, Stasky AA, Hoelscher G, Hanley EN Jr (1997) Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res 235:13–21

    Article  PubMed  CAS  Google Scholar 

  53. Maldonado BA, Oegema TR Jr (1992) Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res 10:677–690

    Article  PubMed  CAS  Google Scholar 

  54. Gruber HE, Leslie K, Ingram J, Hoelscher G, Norton HJ, Hanley EN Jr (2004) Colony formation and matrix production by human anulus cells: modulation in three-dimensional culture. Spine (Phila Pa 1976) 29:E267–E274

    Article  Google Scholar 

  55. Mizuno H, Roy AK, Vacanti CA, Kojima K, Ueda M, Bonassar LJ (2004) Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine (Phila Pa 1976) 29:1290–1297 discussion 1297–8

    Article  Google Scholar 

  56. Yang X, Wang D, Hao J, Gong M, Arlet V, Balian G, Shen FH, Li XJ (2011) Enhancement of matrix production and cell proliferation in human annulus cells under bioreactor culture. Tissue Eng Part A 17:1595–1603

    Article  PubMed  CAS  Google Scholar 

  57. Le Maitre CL, Richardson SM, Baird P, Freemont AJ, Hoyland JA (2005) Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc. J Pathol 207:445–452

    Article  PubMed  CAS  Google Scholar 

  58. Tolonen J, Gronblad M, Vanharanta H, Virri J, Guyer RD, Rytomaa T, Karaharju EO (2006) Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor. Eur Spine J 15:588–596

    Article  PubMed  Google Scholar 

  59. Kim JH, Studer RK, Vo NV, Sowa GA, Kang JD (2009) p38 MAPK inhibition selectively mitigates inflammatory mediators and VEGF production in AF cells co-cultured with activated macrophage-like THP-1 cells. Osteoarthritis Cartilage 17:1662–1669

    Article  PubMed  CAS  Google Scholar 

  60. Gilbert HT, Hoyland JA, Freemont AJ, Millward-Sadler SJ (2011) The involvement of interleukin-1 and interleukin-4 in the response of human annulus fibrosus cells to cyclic tensile strain: an altered mechanotransduction pathway with degeneration. Arthritis Res Ther 13:R8

    Article  PubMed  CAS  Google Scholar 

  61. Hegewald AA, Neumann K, Kalwitz G, Freymann U, Endres M, Schmieder K, Kaps C, Thome C (2011) The chemokines CXCL10 and XCL1 recruit human annulus fibrosus cells. Spine (Phila Pa 1976) 37(2):101–107

    Article  Google Scholar 

  62. Thonar E, An H, Masuda K (2002) Compartmentalization of the matrix formed by nucleus pulposus and annulus fibrosus cells in alginate gel. Biochem Soc Trans 30:874–878

    Article  PubMed  CAS  Google Scholar 

  63. Thompson JP, Oegema TR Jr, Bradford DS (1991) Stimulation of mature canine intervertebral disc by growth factors. Spine (Phila Pa 1976) 16:253–260

    Article  CAS  Google Scholar 

  64. Masuda K, Takegami K, An H, Kumano F, Chiba K, Andersson GB, Schmid T, Thonar E (2003) Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads. J Orthop Res 21:922–930

    Article  PubMed  CAS  Google Scholar 

  65. Masuda K, An HS (2006) Prevention of disc degeneration with growth factors. Eur Spine J 15(Suppl 3):S422–S432

    Article  PubMed  Google Scholar 

  66. Takegami K, An HS, Kumano F, Chiba K, Thonar EJ, Singh K, Masuda K (2005) Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis. Spine J 5:231–238

    Article  PubMed  Google Scholar 

  67. Gilbertson L, Ahn SH, Teng PN, Studer RK, Niyibizi C, Kang JD (2008) The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J 8:449–456

    Article  PubMed  Google Scholar 

  68. Cui M, Wan Y, Anderson DG, Shen FH, Leo BM, Laurencin CT, Balian G, Li X (2008) Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression. Spine J 8:287–295

    Article  PubMed  Google Scholar 

  69. Shen FH, Zeng Q, Lv Q, Choi L, Balian G, Li X, Laurencin CT (2006) Osteogenic differentiation of adipose-derived stromal cells treated with GDF-5 cultured on a novel three-dimensional sintered microsphere matrix. Spine J 6:615–623

    Article  PubMed  Google Scholar 

  70. Walsh AJ, Bradford DS, Lotz JC (2004) In vivo growth factor treatment of degenerated intervertebral discs. Spine (Phila Pa 1976) 29:156–163

    Article  Google Scholar 

  71. Hayes AJ, Ralphs JR (2011) The response of foetal annulus fibrosus cells to growth factors: modulation of matrix synthesis by TGF-beta1 and IGF-1. Histochem Cell Biol 136:163–175

    Article  PubMed  CAS  Google Scholar 

  72. Masuda K, An HS (2004) Growth factors and the intervertebral disc. Spine J 4:330S–340S

    Article  PubMed  Google Scholar 

  73. Osada R, Ohshima H, Ishihara H, Yudoh K, Sakai K, Matsui H, Tsuji H (1996) Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs. J Orthop Res 14:690–699

    Article  PubMed  CAS  Google Scholar 

  74. Pratsinis H, Kletsas D (2007) PDGF, bFGF and IGF-I stimulate the proliferation of intervertebral disc cells in vitro via the activation of the ERK and akt signaling pathways. Eur Spine J 16:1858–1866

    Article  PubMed  Google Scholar 

  75. Chujo T, An HS, Akeda K, Miyamoto K, Muehleman C, Attawia M, Andersson G, Masuda K (2006) Effects of growth differentiation factor-5 on the intervertebral disc–in vitro bovine study and in vivo rabbit disc degeneration model study. Spine (Phila Pa 1976) 31:2909–2917

    Article  Google Scholar 

  76. Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD (2008) Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 8:888–896

    Article  PubMed  Google Scholar 

  77. Tim Yoon S, Su Kim K, Li J, Soo Park J, Akamaru T, Elmer WA, Hutton WC (2003) The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine (Phila Pa 1976) 28:1773–1780

    Article  CAS  Google Scholar 

  78. Zhang Y, Anderson DG, Phillips FM, Thonar EJ, He TC, Pietryla D, An HS (2007) Comparative effects of bone morphogenetic proteins and Sox9 overexpression on matrix accumulation by bovine anulus fibrosus cells: implications for anular repair. Spine (Phila Pa 1976) 32:2515–2520

    Article  Google Scholar 

  79. Li X, Leo BM, Beck G, Balian G, Anderson GD (2004) Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular changes when treating disk cells with recombinant growth factor. Spine (Phila Pa 1976) 29:2229–2234

    Article  Google Scholar 

  80. Feng G, Wan Y, Balian G, Laurencin CT, Li X (2008) Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells. Growth Factors 26:132–142

    Article  PubMed  CAS  Google Scholar 

  81. Liang H, Ma SY, Feng G, Shen FH, Joshua Li X (2010) Therapeutic effects of adenovirus-mediated growth and differentiation factor-5 in a mice disc degeneration model induced by annulus needle puncture. Spine J 10:32–41

    Article  PubMed  Google Scholar 

  82. Mwale F, Demers CN, Petit A, Roughley P, Poole AR, Steffen T, Aebi M, Antoniou J (2003) A synthetic peptide of link protein stimulates the biosynthesis of collagens II, IX and proteoglycan by cells of the intervertebral disc. J Cell Biochem 88:1202–1213

    Article  PubMed  CAS  Google Scholar 

  83. Mwale F, Masuda K, Pichika R, Epure LM, Yoshikawa T, Hemmad A, Roughley PJ, Antoniou J (2011) The efficacy of link N as a mediator of repair in a rabbit model of intervertebral disc degeneration. Arthritis Res Ther 13:R120

    Article  PubMed  Google Scholar 

  84. Petit A, Yao G, Rowas SA, Gawri R, Epure L, Antoniou J, Mwale F (2011) Effect of synthetic link N peptide on the expression of type I and type II collagens in human intervertebral disc cells. Tissue Eng Part A 17:899–904

    Article  PubMed  CAS  Google Scholar 

  85. Sato M, Kikuchi M, Ishihara M, Ishihara M, Asazuma T, Kikuchi T, Masuoka K, Hattori H, Fujikawa K (2003) Tissue engineering of the intervertebral disc with cultured annulus fibrosus cells using atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS scaffold). Med Biol Eng Comput 41:365–371

    Article  PubMed  CAS  Google Scholar 

  86. Sato M, Asazuma T, Ishihara M, Ishihara M, Kikuchi T, Kikuchi M, Fujikawa K (2003) An experimental study of the regeneration of the intervertebral disc with an allograft of cultured annulus fibrosus cells using a tissue-engineering method. Spine (Phila Pa 1976) 28:548–553

    Google Scholar 

  87. Saad L, Spector M (2004) Effects of collagen type on the behavior of adult canine annulus fibrosus cells in collagen-glycosaminoglycan scaffolds. J Biomed Mater Res A 71:233–241

    Article  PubMed  CAS  Google Scholar 

  88. Shao X, Hunter CJ (2007) Developing an alginate/chitosan hybrid fiber scaffold for annulus fibrosus cells. J Biomed Mater Res A 82:701–710

    PubMed  Google Scholar 

  89. Wan Y, Feng G, Shen FH, Balian G, Laurencin CT, Li X (2007) Novel biodegradable poly(1,8-octanediol malate) for annulus fibrosus regeneration. Macromol Biosci 7:1217–1224

    Article  PubMed  CAS  Google Scholar 

  90. Helen W, Gough JE (2008) Cell viability, proliferation and extracellular matrix production of human annulus fibrosus cells cultured within PDLLA/Bioglass composite foam scaffolds in vitro. Acta Biomater 4:230–243

    Article  PubMed  CAS  Google Scholar 

  91. Helen W, Merry CL, Blaker JJ, Gough JE (2007) Three-dimensional culture of annulus fibrosus cells within PDLLA/Bioglass composite foam scaffolds: assessment of cell attachment, proliferation and extracellular matrix production. Biomaterials 28:2010–2020

    Article  PubMed  CAS  Google Scholar 

  92. Chang G, Kim HJ, Vunjak-Novakovic G, Kaplan DL, Kandel R (2010) Enhancing annulus fibrosus tissue formation in porous silk scaffolds. J Biomed Mater Res A 92:43–51

    PubMed  Google Scholar 

  93. Chang G, Kim HJ, Kaplan D, Vunjak-Novakovic G, Kandel RA (2007) Porous silk scaffolds can be used for tissue engineering annulus fibrosus. Eur Spine J 16:1848–1857

    Article  PubMed  CAS  Google Scholar 

  94. Schek RM, Michalek AJ, Iatridis JC (2011) Genipin-crosslinked fibrin hydrogels as a potential adhesive to augment intervertebral disc annulus repair. Eur Cell Mater 21:373–383

    PubMed  CAS  Google Scholar 

  95. Yang L, Kandel RA, Chang G, Santerre JP (2009) Polar surface chemistry of nanofibrous polyurethane scaffold affects annulus fibrosus cell attachment and early matrix accumulation. J Biomed Mater Res A 91:1089–1099

    PubMed  Google Scholar 

  96. Yeganegi M, Kandel RA, Santerre JP (2010) Characterization of a biodegradable electrospun polyurethane nanofiber scaffold: mechanical properties and cytotoxicity. Acta Biomater 6:3847–3855

    Article  PubMed  CAS  Google Scholar 

  97. Koepsell L, Zhang L, Neufeld D, Fong H, Deng Y (2011) Electrospun nanofibrous polycaprolactone scaffolds for tissue engineering of annulus fibrosus. Macromol Biosci 11:391–399

    Article  PubMed  CAS  Google Scholar 

  98. Nerurkar NL, Elliott DM, Mauck RL (2007) Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res 25:1018–1028

    Article  PubMed  CAS  Google Scholar 

  99. Vadala G, Mozetic P, Rainer A, Centola M, Loppini M, Trombetta M, Denaro V (2012) Bioactive electrospun scaffold for annulus fibrosus repair and regeneration. Eur Spine J 21(Suppl 1):S20–S26

    Article  PubMed  Google Scholar 

  100. Bhattacharjee M, Miot S, Gorecka A, Singha K, Loparic M, Dickinson S, Das A, Bhavesh NS, Ray AR, Martin I, Ghosh S (2012) Oriented lamellar silk fibrous scaffolds to drive cartilage matrix orientation: towards annulus fibrosus tissue engineering. Acta Biomater 8:3313–3325

    Article  PubMed  CAS  Google Scholar 

  101. Saeidi N, Karmelek KP, Paten JA, Zareian R, Dimasi E, Ruberti JW (2012) Molecular crowding of collagen: a pathway to produce highly-organized collagenous structures. Biomaterials 33:7366–7374

    Article  PubMed  CAS  Google Scholar 

  102. Wan Y, Feng G, Shen FH, Laurencin CT, Li X (2008) Biphasic scaffold for annulus fibrosus tissue regeneration. Biomaterials 29:643–652

    Article  PubMed  CAS  Google Scholar 

  103. Mizuno H, Roy AK, Zaporojan V, Vacanti CA, Ueda M, Bonassar LJ (2006) Biomechanical and biochemical characterization of composite tissue-engineered intervertebral discs. Biomaterials 27:362–370

    Article  PubMed  CAS  Google Scholar 

  104. See EY, Toh SL, Goh JC (2012) Simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell sheets and silk scaffolds for annulus fibrosus regeneration. J Tissue Eng Regen Med 6:528–535

    Google Scholar 

  105. Park SH, Gil ES, Cho H, Mandal BB, Tien LW, Min BH, Kaplan DL (2012) Intervertebral disk tissue engineering using biphasic silk composite scaffolds. Tissue Eng Part A 18:447–458

    Article  PubMed  CAS  Google Scholar 

  106. Bowles RD, Gebhard HH, Dyke JP, Ballon DJ, Tomasino A, Cunningham ME, Hartl R, Bonassar LJ (2011) Image-based tissue engineering of a total intervertebral disc implant for restoration of function to the rat lumbar spine. NMR Biomed 25(3):443–451

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We apologize for not citing all of the important contributions to this field due to space limitations. We deeply appreciate Mrs. Janet Stack and Mr. Phillip Scott for their editing assistance. We thank the financial support from AO International and AONA Young Investigator Award.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Virginia, Hospital Drive, Cobb Hall B039, P.O. Box 800374, 22908, Charlottesville, VA, USA

    Li Jin, Adam L. Shimmer & Xudong Li

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  1. Li Jin
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  2. Adam L. Shimmer
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  3. Xudong Li
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Correspondence to Xudong Li.

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Jin, L., Shimmer, A.L. & Li, X. The challenge and advancement of annulus fibrosus tissue engineering. Eur Spine J 22, 1090–1100 (2013). https://doi.org/10.1007/s00586-013-2663-2

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  • DOI: https://doi.org/10.1007/s00586-013-2663-2

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