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Strategies towards injectable, load-bearing materials for the intervertebral disc: a review and outlook

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Abstract

Currently available treatments for the degenerated intervertebral disc present disadvantages, such as surgical invasiveness and inadequate load distribution results. Load-bearing, injectable materials may be interesting for future therapies, but have not been studied in depth. In this study, the existing literature was screened for studies on injectable materials for the intervertebral disc and a rationale for load-bearing, injectable materials was formulated. Requirements for such a material were discussed, partly based on the experience of materials used for similar applications. Important properties were discussed and found to include biocompatibility, bioactivity, porosity, handling, injectability, working time, setting time, radiopacity, containment and mechanical properties, where several of these properties are linked to one another. In conclusion, there is a need for consensus on the properties of new materials developed for use in minimally invasive procedures in the spine. A substantial amount of attention may need to be given to non-toxic setting reactions.

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References

  1. Bjorck-van Dijken C, Fjellman-Wiklund A, Hildingsson C. Low back pain, lifestyle factors and physical activity: a population based-study. J Rehabil Med. 2008;40(10):864–9. doi:10.2340/16501977-0273.

    Google Scholar 

  2. Brisby H. Pathology and possible mechanisms of nervous system response to disc degeneration. J Bone Joint Surg. 2006;88:68–71.

    Article  Google Scholar 

  3. Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976). 2006;31(18):2151–61. doi:10.1097/01.brs.0000231761.73859.2c.

    Article  Google Scholar 

  4. Bouwmeester W, van Enst A, van Tulder M. Quality of low back pain guidelines improved. Spine (Phila Pa 1976). 2009;34(23):2562–7. doi:10.1097/BRS.0b013e3181b4d50d.

    Article  Google Scholar 

  5. Bao QB, McCullen GM, Higham PA, Dumbleton JH, Yuan HA. The artificial disc: theory, design and materials. Biomaterials. 1996;17(12):1157–67.

    Article  CAS  Google Scholar 

  6. Shikinami Y, Kotani Y, Cunningham BW, Abumi K, Kaneda K. A biomimetic artificial disc with improved mechanical properties compared to biological intervertebral discs. Adv Funct Mater. 2004;14(11):1039–46. doi:10.1002/adfm.200305038.

    Article  CAS  Google Scholar 

  7. Gloria A, Causa F, De Santis R, Netti PA, Ambrosio L. Dynamic-mechanical properties of a novel composite intervertebral disc prosthesis. J Mater Sci Mater Med. 2007;18(11):2159–65. doi:10.1007/s10856-007-3003-z.

    Article  CAS  Google Scholar 

  8. Gloria A, Santis RD, Ambrosio L, Causa F, Tanner KE. A multi-component fiber-reinforced PHEMA-based hydrogel/HAPEXTM device for customized intervertebral disc prosthesis. J Biomater Appl. 2010;. doi:10.1177/0885328209360933.

    Google Scholar 

  9. Ghiselli G, Wang JC, Bhatia NN, Hsu WK, Dawson EG. Adjacent segment degeneration in the lumbar spine. J Bone Joint Surg Am. 2004;86–A(7):1497–503.

    Google Scholar 

  10. Gillet P. The fate of the adjacent motion segments after lumbar fusion. J Spinal Disord Tech. 2003;16(4):338–45.

    Article  Google Scholar 

  11. Park P, Garton HJ, Gala VC, Hoff JT, McGillicuddy JE. Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature. Spine (Phila Pa 1976). 2004;29(17):1938–44.

    Article  Google Scholar 

  12. Siepe CJ, Zelenkov P, Sauri-Barraza JC, Szeimies U, Grubinger T, Tepass A, et al. The fate of facet joint and adjacent level disc degeneration following total lumbar disc replacement: a prospective clinical, X-ray, and magnetic resonance imaging investigation. Spine (Phila Pa 1976). 2010;35(22):1991–2003. doi:10.1097/BRS.0b013e3181d6f878.

    Article  Google Scholar 

  13. Nyqvist C, Berg S, Tropp H, editors. Total disc replacement compared to lumbar fusion: a randomised controlled trial with five-year follow-up. ISASS 12; 2012; Barcelona.

  14. Sakalkale DP, Bhagia SA, Slipman CW. A historical review and current perspective on the intervertebral disc prosthesis. Pain Physician. 2003;6(2):195–8.

    Google Scholar 

  15. Bao QB, Yuan HA. Artificial disc technology. Neurosurg Focus. 2000;9(4):e14.

    Article  CAS  Google Scholar 

  16. van den Eerenbeemt KD, Ostelo RW, van Royen BJ, Peul WC, van Tulder MW. Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature. Eur Spine J. 2010;19(8):1262–80. doi:10.1007/s00586-010-1445-3.

    Article  Google Scholar 

  17. van Ooij A, Oner FC, Verbout AJ. Complications of artificial disc replacement: a report of 27 patients with the SB charite disc. J Spinal Disord Tech. 2003;16(4):369–83.

    Article  Google Scholar 

  18. Kurtz SM, Peloza J, Siskey R, Villarraga ML. Analysis of a retrieved polyethylene total disc replacement component. Spine J. 2005;5(3):344–50. doi:10.1016/j.spinee.2004.11.011.

    Article  Google Scholar 

  19. Guyer RD, Shellock J, MacLennan B, Hanscom D, Knight RQ, McCombe P, et al. Early failure of metal-on-metal artificial disc prostheses associated with lymphocytic reaction: diagnosis and treatment experience in four cases. Spine (Phila Pa 1976). 2011;36(7):E492–7. doi:10.1097/BRS.0b013e31820ea9a2.

    Article  Google Scholar 

  20. Cavanaugh DA, Nunley PD, Kerr EJ 3rd, Werner DJ, Jawahar A. Delayed hyper-reactivity to metal ions after cervical disc arthroplasty: a case report and literature review. Spine (Phila Pa 1976). 2009;34(7):E262–5. doi:10.1097/BRS.0b013e318195dd60.

    Article  Google Scholar 

  21. Berry MR, Peterson BG, Alander DH. A granulomatous mass surrounding a Maverick total disc replacement causing iliac vein occlusion and spinal stenosis: a case report. J Bone Joint Surg Am. 2010;92(5):1242–5. doi:10.2106/jbjs.h.01625.

    Article  Google Scholar 

  22. Kurtz SM, Edidin AA. Spine technology handbook. Amsterdam: Elsevier Academic Press; 2006.

    Google Scholar 

  23. Masuda K, Imai Y, Okuma M, Muehleman C, Nakagawa K, Akeda K, et al. Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model. Spine (Phila Pa 1976). 2006;31(7):742–54. doi:10.1097/01.brs.0000206358.66412.7b.

    Article  Google Scholar 

  24. Bertram H, Kroeber M, Wang H, Unglaub F, Guehring T, Carstens C, et al. Matrix-assisted cell transfer for intervertebral disc cell therapy. Biochem Biophys Res Commun. 2005;331(4):1185–92. doi:10.1016/j.bbrc.2005.04.034.

    Article  CAS  Google Scholar 

  25. Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med. 2011;. doi:10.1002/term.433.

    Google Scholar 

  26. Scholz B, Kinzelmann C, Benz K, Mollenhauer J, Wurst H, Schlosshauer B. Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration. Eur Cell Mater. 2010;20:24–36; discussion-7.

    Google Scholar 

  27. Gloria A, Borzacchiello A, Causa F, Ambrosio L. Rheological characterization of hyaluronic acid derivatives as injectable materials toward nucleus pulposus regeneration. J Biomater Appl. 2012;26(6):745–59. doi:10.1177/0885328210387174.

    Article  CAS  Google Scholar 

  28. Revell PA, Damien E, Di Silvio L, Gurav N, Longinotti C, Ambrosio L. Tissue engineered intervertebral disc repair in the pig using injectable polymers. J Mater Sci Mater Med. 2007;18(2):303–8. doi:10.1007/s10856-006-0693-6.

    Article  CAS  Google Scholar 

  29. Vernengo J, Fussell GW, Smith NG, Lowman AM. Synthesis and characterization of injectable bioadhesive hydrogels for nucleus pulposus replacement and repair of the damaged intervertebral disc. J Biomed Mater Res B Appl Biomater. 2010;93(2):309–17. doi:10.1002/jbm.b.31547.

    CAS  Google Scholar 

  30. Berlemann U, Schwarzenbach O. An injectable nucleus replacement as an adjunct to microdiscectomy: 2 year follow-up in a pilot clinical study. Eur Spine J. 2009;18(11):1706–12. doi:10.1007/s00586-009-1136-0.

    Article  Google Scholar 

  31. Lindley EM, Jaafar S, Noshchenko A, Baldini T, Nair DP, Shandas R, et al. Nucleus replacement device failure: a case report and biomechanical study. Spine (Phila Pa 1976). 2010;35(22):E1241–7. doi:10.1097/BRS.0b013e3181dfbc78.

    Article  Google Scholar 

  32. Baumgartner W, inventor US Patent 5171280: intervertebral prosthesis. 1992.

  33. Shimamura Y, Holding C, Haynes DR, Vernon-Roberts B, Blumbergs PC, Fraser RD, et al. The biologic response to particles from a potential disc prosthesis material. Spine (Phila Pa 1976). 2008;33(4):351–5. doi:10.1097/BRS.0b013e318163f323.

    Article  Google Scholar 

  34. Zollner J, Eysel P, inventors; US6520992: utilization of an autopolymerizing organosiloxane-based compound. 2003.

  35. Larraz E, Elvira C, Fernandez M, Parra J, Collia F, Lopez-Bravo A, et al. Self-curing acrylic formulations with applications in intervertebral disk restoration: drug release and biological behaviour. J Tissue Eng Regen Med. 2007;1(2):120–7. doi:10.1002/term.10.

    Article  CAS  Google Scholar 

  36. Larraz E, Elvira C, Roman JS. Design and properties of novel self-curing acrylic formulations for application in intervertebral disks restoration. Biomacromolecules. 2005;6(4):2058–66. doi:10.1021/bm050055z.

    Article  CAS  Google Scholar 

  37. López A, Persson C, Hilborn J, Engqvist H. Synthesis and characterization of injectable composites of poly[d, l-lactide-co-(ε-caprolactone)] reinforced with β-TCP and CaCO3 for intervertebral disk augmentation. J Biomed Mater Res B Appl Biomater. 2010;95(1):75–83.

    Google Scholar 

  38. Tsantrizos A, Ordway NR, Myint K, Martz E, Yuan HA. Mechanical and biomechanical characterization of a polyurethane nucleus replacement device injected and cured in situ within a balloon. SAS J. 2008;2(1):28–39.

    Article  Google Scholar 

  39. Peebles DJ, Ellis RH, Stride SD, Simpson BR. Cardiovascular effects of methylmethacrylate cement. Br Med J. 1972;1(5796):349–51.

    Article  CAS  Google Scholar 

  40. Nomura Y, Teshima W, Kawahara T, Tanaka N, Ishibashi H, Okazaki M, et al. Genotoxicity of dental resin polymerization initiators in vitro. J Mater Sci Mater Med. 2006;17(1):29–32. doi:10.1007/s10856-006-6326-2.

    Article  CAS  Google Scholar 

  41. Blattert TR, Jestaedt L, Weckbach A. Suitability of a calcium phosphate cement in osteoporotic vertebral body fracture augmentation: a controlled, randomized, clinical trial of balloon kyphoplasty comparing calcium phosphate versus polymethylmethacrylate. Spine (Phila Pa 1976). 2009;34(2):108–14. doi:10.1097/BRS.0b013e31818f8bc1.

    Article  Google Scholar 

  42. Li S, Chien S, Branemark PI. Heat shock-induced necrosis and apoptosis in osteoblasts. J Orthop Res. 1999;17(6):891–9. doi:10.1002/jor.1100170614.

    Article  CAS  Google Scholar 

  43. ISO10993. Biological evaluation of medical devices: international organization for standardization. 2001.

  44. Ahrens M, Tsantrizos A, Donkersloot P, Martens F, Lauweryns P, Le Huec JC, et al. 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). 2009;34(13):1376–84. doi:10.1097/BRS.0b013e3181a3967f.

    Article  Google Scholar 

  45. Lewis G. Injectable bone cements for use in vertebroplasty and kyphoplasty: state-of-the-art review. J Biomed Mater Res B Appl Biomater. 2006;76(2):456–68. doi:10.1002/jbm.b.30398.

    Google Scholar 

  46. Lewis G, Mladsi S. Effect of sterilization method on properties of Palacos R acrylic bone cement. Biomaterials. 1998;19(1–3):117–24.

    Article  CAS  Google Scholar 

  47. del Valle S, Mino N, Munoz F, Gonzalez A, Planell JA, Ginebra MP. In vivo evaluation of an injectable macroporous calcium phosphate cement. J Mater Sci Mater Med. 2007;18(2):353–61. doi:10.1007/s10856-006-0700-y.

    Article  Google Scholar 

  48. Takagi S, Chow LC, Hirayama S, Sugawara A. Premixed calcium-phosphate cement pastes. J Biomed Mater Res B Appl Biomater. 2003;67(2):689–96.

    Article  Google Scholar 

  49. Gbureck U, Dembski S, Thull R, Barralet JE. Factors influencing calcium phosphate cement shelf-life. Biomaterials. 2005;26(17):3691–7. doi:10.1016/j.biomaterials.2004.09.036.

    Article  CAS  Google Scholar 

  50. Eckel TS, Olan W. Vertebroplasty and vertebral augmentation techniques. Tech Vasc Interv Radiol. 2009;12(1):44–50.

    Article  Google Scholar 

  51. Dang L, Wardlaw D, Hukins DW. Removal of nucleus pulposus from the intervertebral disc—the use of chymopapain enhances mechanical removal with rongeurs: a laboratory study. BMC Musculoskelet Disord. 2007;8:122. doi:10.1186/1471-2474-8-122.

    Article  Google Scholar 

  52. Sherman J, Horton C, Norton B, editors. Initial cadaver evaluation of a mechanical nucleus removal device. Annual Meeting of the Spine Arthroplasty Society; 2008; Miami Beach, FL.

  53. Carrodeguas RG, Lasa BV, Del Barrio JS. Injectable acrylic bone cements for vertebroplasty with improved properties. J Biomed Mater Res B Appl Biomater. 2004;68(1):94–104. doi:10.1002/jbm.b.20007.

    Article  Google Scholar 

  54. Gbureck U, Spatz K, Thull R, Barralet JE. Rheological enhancement of mechanically activated alpha-tricalcium phosphate cements. J Biomed Mater Res B Appl Biomater. 2005;73(1):1–6. doi:10.1002/jbm.b.30148.

    CAS  Google Scholar 

  55. Loeffel M, Heini PF, Bouduban N, Burger J, Nolte LP, Kowal J. Development of a computer-assisted high-pressure injection device for vertebroplasty. IEEE Trans Biomed Eng. 2007;54(11):2051–6. doi:10.1109/TBME.2007.894964.

    Article  Google Scholar 

  56. Unosson E. Mechanical properties and spreading characteristics of bone cement for spinal applications. Luleå: Luleå University of Technology; 2010.

    Google Scholar 

  57. ASTM F 451-08. Standard specification for acrylic bone cement. American Society for Testing and Materials; 2008.

  58. ASTM C 266-99. Standard test method for time of setting of hydraulic-cement paste by Gillmore needles. American Society for Testing and Materials; 1999.

  59. Morgan EF, Yetkinler DN, Constantz BR, Dauskardt RH. Mechanical properties of carbonated apatite bone mineral substitute: strength, fracture and fatigue behaviour. J Mater Sci Mater Med. 1997;8(9):559–70.

    Article  CAS  Google Scholar 

  60. Scuderi GJ, Brusovanik GV, Campbell DR, Henry RP, Kwon B, Vaccaro AR. Evaluation of non-lead-based protective radiological material in spinal surgery. Spine J. 2006;6(5):577–82. doi:10.1016/j.spinee.2005.09.010.

    Article  Google Scholar 

  61. Boelen EJ, Lewis G, Xu J, Slots T, Koole LH, van Hooy-Corstjens CS. Evaluation of a highly-radiopaque iodine-containing acrylic bone cement for use in augmentation of vertebral compression fractures. J Biomed Mater Res A. 2008;86(1):76–88. doi:10.1002/jbm.a.31601.

    Google Scholar 

  62. Lewis G, Towler MR, Boyd D, German MJ, Wren AW, Clarkin OM, et al. Evaluation of two novel aluminum-free, zinc-based glass polyalkenoate cements as alternatives to PMMA bone cement for use in vertebroplasty and balloon kyphoplasty. J Mater Sci Mater Med. 2009;. doi:10.1007/s10856-009-3845-7.

    Google Scholar 

  63. López A, Montazerolghaem M, Ott M, Engqvist H, Persson C. Strontium halides as degradable radiopacifiers. GRIBOI; Uppsala: European Cells and Materials; 2012. S3, p. 45.

  64. Johannessen W, Elliott DM. Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine (Phila Pa 1976). 2005;30(24):E724–9.

    Article  Google Scholar 

  65. Guerin HA, Elliott DM. Degeneration affects the fiber reorientation of human annulus fibrosus under tensile load. J Biomech. 2006;39(8):1410–8. doi:10.1016/j.jbiomech.2005.04.007.

    Article  Google Scholar 

  66. Wilke H-J, Neef P, Caimi M, Hoogland T, Claes LE. New in vivo measurements of pressures in the intervertebral disc in daily life. Spine. 1999;24(8):755–62.

    Article  CAS  Google Scholar 

  67. ASTM F2423: Standard guide for functional, kinematic, and wear assessment of total disc prostheses; 2005.

  68. ISO 18192. Implants for surgery—wear of total intervertebral spinal disc prostheses—part 1: loading and displacement parameters for wear testing and corresponding environmental conditions for test; 2008.

  69. ASTM F2118-03. Standard test method for constant amplitude of force controlled fatigue testing of acrylic bone cement materials; 2009.

  70. Hulme PA, Boyd SK, Ferguson SJ. Regional variation in vertebral bone morphology and its contribution to vertebral fracture strength. Bone. 2007;41(6):946–57. doi:10.1016/j.bone.2007.08.019.

    Article  CAS  Google Scholar 

  71. ISO5833. Implants for surgery—acrylic resin cements. The International Organization for Standardization; 2002.

  72. Zhang Z, Kuijer R, Bulstra SK, Grijpma DW, Feijen J. The in vivo and in vitro degradation behavior of poly(trimethylene carbonate). Biomaterials. 2006;27(9):1741–8. doi:10.1016/j.biomaterials.2005.09.017.

    Article  CAS  Google Scholar 

  73. Engstrand J, López A, Engqvist H, Persson C. Polyhedral oligomeric silsesquioxane (POSS)—poly(ethylene glycol) (PEG) hybrids as injectable biomaterials. Biomed Mater. 2012;7(3). doi:10.1088/1748-6041/7/3/035013.

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Funding from the Carl Trygger Foundation is gratefully acknowledged.

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Correspondence to Cecilia Persson.

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Persson, C., Berg, S. Strategies towards injectable, load-bearing materials for the intervertebral disc: a review and outlook. J Mater Sci: Mater Med 24, 1–10 (2013). https://doi.org/10.1007/s10856-012-4776-2

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