Skip to main content

Recent Advances in Regenerative Approaches to Intervertebral Disc Degeneration

  • Chapter
  • First Online:
Biomedical Engineering: Frontier Research and Converging Technologies

Part of the book series: Biosystems & Biorobotics ((BIOSYSROB,volume 9))

  • 2392 Accesses

Abstract

Intervertebral disc (IVD) degeneration is one of the major neurodegenerative diseases throughout the world. Development of new and advanced treatment methods are highly warranted due to the limitations of conventional protocols. Very recently, regenerative medicine techniques based on biomaterials, stem cell and bioactive molecules have been demonstrated as the most powerful concept to regenerate IVD. In this chapter, we will review the recent progress in (1) biomaterial scaffolds for annulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous end plates (CEP), (2) stem cells as cell sources, and finally introduce (3) our recent research studies focusing on the fabrication of natural/synthetic hybrid scaffolds for various purposes during the last 5 years.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Sakai, D., Anderson, G.B.J.: Stem cell therapy for intervertebral disc regeneration: obstacles and solution. Nat. Rev. Rheumatol. (2015). doi:10.1038/nrrheum.2015.13

    Google Scholar 

  2. Maidhof, R., Alipui, D.O., Rafiuddin, A., Levine, M., Grande, D.A., Chahine, N.O.: Emerging trends in biological therapy for intervertebral disc degeneration. Discov. Med. 14, 401–411 (2012)

    Google Scholar 

  3. Kalson, N.S., Richardson, S., Hoyland, J.A.: Strategies for regeneration of the intervertebral disc. Regen. Medicine 3, 717–729 (2008)

    Article  Google Scholar 

  4. Wei, A., Shen, B., Williams, L., Diwan, A.: Mesenchymal stem cells: potential application in intervertebral disc regeneration. Transl. Pediatr. 3, 71–90 (2014)

    Google Scholar 

  5. Huang, Y.C., Urban, J.P., Luk, K.D.: Intervertebral disc regeneration: do nutrients lead the way? Nat. Rev. Rheumatol. 10, 561–566 (2014)

    Article  Google Scholar 

  6. Whatley, B.R., Wen, X.: Intervertebral disc (IVD): Structure, degeneration, repair and regeneration. Mater. Sci. Eng. C32, 61–77 (2012)

    Article  Google Scholar 

  7. Iatridis, J.C., Nicoll, S.B., Michalek, A.J., Walter, B.A., Gupta, M.S.: Role of biomechanics in intervertebral disc degeneration and regenerative therapies: what needs repairing in the disc and what are promising biomaterials for its repair? The Spine J. 13, 243–262 (2013)

    Article  Google Scholar 

  8. Nerurkar, N.L., Elliott, D.M., Mauck, R.L.: Mechanical design criteria for intervertebral disc tissue engineering. J Biomechan. 43, 1017–1030 (2010)

    Article  Google Scholar 

  9. Kepler, C.K., Ponnappan, R.K., Tannoury, C.A., Risbud, M.V., Anderson, D.G.: The molecular basis of intervertebral disc degeneration. The Spine J. 13, 318–330 (2013)

    Article  Google Scholar 

  10. Broek, P.R., Huyghe, J.M., Wilson, W., Ito, K.: Design of next generation total disk replacements. J. Biomechan. 45, 134–140 (2012)

    Article  Google Scholar 

  11. Sharifi, S., Bulstra, S.K., Grijpma, D.W., Kuijer, R.: Treatment of the degenerated intervertebral disc; closure, repair and regeneration of the annulus fibrosus. J. Tissue Eng. Regen. Med. (2014) doi:10.1002/term.1866

    Google Scholar 

  12. Khang, G., Kim, M.S., Lee, H.B.: Manuals in Biomedical Research, vol. 4. A Manual for Biomaterials/Scaffold Fabrication Technology. World Scientific, Singapore (2007)

    Google Scholar 

  13. Khang, G., Kim, S.H., Kim, M.S., Lee, H.B.: Hybrid, composite, and complex biomaterials for scaffolds. In: Lanza, R., Atala, A., Nerem, R., Thomson, W. (eds) Principles of Regenerative Medicine, pp 636−655. Academic Press. New York (2008)

    Google Scholar 

  14. Khang, G.: chap 1, introduction. In: Khang, G. (ed.) Handbook of Intelligent Scaffold for Tissue Engineering & Regenerative Medicine, pp 3−40. Pan Stanford Pub., New York (2012)

    Google Scholar 

  15. Khang, G., Shimizu, T:. Manuals for Differentiation of Bone Marrow-Derived Stem Cell to Specific Cell Types. World Scientific, Singapore (2014)

    Google Scholar 

  16. Khang, G., Kim, S.H., Rhee, J.M., Sha’Ban, M., Idrus, R.B.H.: Chap. synthetic/natural hybrid scaffold for cartilage and DIsc regenerations. In: Tateishi, T. (ed.) Biomaterials in Asia in Commemoration of the 1st Asian Biomaterials Congress World Scientific, Singapore (2008)

    Google Scholar 

  17. Khang, G.: Importance of inflammation reaction of scaffold for the application of regenerative medicine. Inflammation Regeneration 32(5), 178–196 (2012)

    Article  Google Scholar 

  18. Brona, J.L., Vonkb, L.A., Smita, T.H., Koenderinkd, G.H.: Engineering alginate for intervertebral disc repair. J. Mechan. Behavior. Biomed. Mater. 4, 1196–1205 (2011)

    Article  Google Scholar 

  19. Zhuang, Y., Huang, B., Li, C.Q., Liu, L.T., Pan, Y., Zheng, W.J., Luo, G., Zhou, Y.: Construction of tissue-engineered composite intervertebral disc and preliminary morphological and biochemical evaluation. Biochem. Biophys. Res. Comm. 407, 327–332 (2011)

    Article  Google Scholar 

  20. Strange, D.G., Oyen, M.L.: Composite hydrogels for nucleus pulposus tissue engineering. J. Mechan. Behavior Biomed. Mater. 11, 16–26 (2012)

    Article  Google Scholar 

  21. Gorapalli, D., Seth, A., Vournakis, J., Whyne, C., Akens, M., Zhang, A., Demcheva, M., Qamirani, E., Yee, A.: Evaluation of a novel poly N-acetyl glucosamine (pGlcNAc) hydrogel for treatment of the degenerating intervertebral disc. Life Sci. 91, 1328–1335 (2012)

    Article  Google Scholar 

  22. Chen, Y.C., Su, W.Y., Yang, S.H., Gefen, A., Lin, F.H.: In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration. Acta Biomaterialia 9, 5181–5193 (2013)

    Article  Google Scholar 

  23. Li, Z., Kaplan, K.M., Wertzel, A., Peroglio, M., Amit, B., Alini, M., Grad, S., Yayon, A.: Biomimetic fibrin-hyaluronan hydrogels for nucleus pulposus regeneration. Regen. Med. 9(3), 309–326 (2014)

    Article  Google Scholar 

  24. Jeong, C.G., Francisco, A.T., Niu, Z., Mancino, R.L., Craig, S.L., Setton, L.A.: Screening of hyaluronic acid-poly(ethylene glycol) composite hydrogels to support intervertebral disc cell biosynthesis using artificial neural network analysis. Acta Biomater. 10(8), 3421–3430 (2014)

    Article  Google Scholar 

  25. Francisco, A.T., Hwang, P.Y., Jeong, C.G., Jing, L., Chen, J., Setton, L.A.: Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration. Acta Biomater. 10(3), 1102–1111 (2014)

    Article  Google Scholar 

  26. Feng, G., Zhang, Z., Jin, X., Hu, J., Gupte, M.J., Holzwarth, J.M., Ma, P.X.: Regenerating nucleus pulposus of the intervertebral disc using biodegradable nanofibrous polymer scaffolds. Tissue Eng. Part A 18(21–22), 2231–2238 (2012)

    Article  Google Scholar 

  27. Kim, S.H., Song, J.E., Lee, D., Khang, G.: Development of poly(lactide-co-glycolide) scaffold-impregnated small intestinal submucosa with pores that stimulate extracellular matrix production in disc regeneration. J. Tissue Eng. Regen. Med. 8(4), 279–290 (2014)

    Article  Google Scholar 

  28. Pereira, D.R., Silva-Correia, J., Caridade, S.G., Oliveira, J.T., Sousa, R.A., Salgado, A.J., Oliveira, J.M., Mano, J.F., Sousa, N., Reis, R.L.: Development of gellan gum-based microparticles/hydrogel matrices for application in the intervertebral disc regeneration. Tissue Eng. Part C Methods 17(10), 961–972 (2011)

    Article  Google Scholar 

  29. Nagae, M., Ikeda, T., Mikami, Y., Hase, H., Ozawa, H., Matsuda, K., Sakamoto, H., Tabata, Y., Kawata, M., Kubo, T.: Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng. 13(1), 147–158 (2007)

    Article  Google Scholar 

  30. Le Visage, C., Yang, S.H., Kadakia, L., Sieber, A.N., Kostuik, J.P., Leong, K.W.: Small intestinal submucosa as a potential bioscaffold for intervertebral disc regeneration. Spine(Phila Pa 1976) 31(21), 2423–2430 (2006)

    Article  Google Scholar 

  31. Chen, W.H., Liu, H.Y., Lo, W.C., Wu, S.C., Chi, C.H., Chang, H.Y., Hsiao, S.H., Wu, C.H., Chiu, W.T., Chen, B.J., Deng, W.P.: Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 30(29), 5523–5533 (2009)

    Article  Google Scholar 

  32. Cai, F., Wu, X.T., Xie, X.H., Wang, F., Hong, X., Zhuang, S.Y., Zhu, L., Rui, Y.F., Shi, R.: Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits. Int. Orthop., August 13 2014 (Epub ahead of print)

    Google Scholar 

  33. Kumar, D., Gerges, I., Tamplenizza, M., Lenardi, C., Forsyth, N.R., Liu, Y.: Three-dimensional hypoxic culture of human mesenchymal stem cells encapsulated in a photocurable, biodegradable polymer hydrogel: a potential injectable cellular product for nucleus pulposus regeneration. Acta Biomater. 10(8), 3463–3474 (2014)

    Article  Google Scholar 

  34. Frith, J.E., Cameron, A.R., Menzies, D.J., Ghosh, P., Whitehead, D.L., Gronthos, S., Zannettino, A.C., Cooper-White, J.J.: An injectable hydrogel incorporating mesenchymal precursor cells and pentosan polysulphate for intervertebral disc regeneration. Biomaterials 34(37), 9430–9440 (2013)

    Article  Google Scholar 

  35. Wang, H., Zhou, Y., Huang, B., Liu, L.T., Liu, M.H., Wang, J., Li, C.Q., Zhang, Z.F., Chu, T.W., Xiong, C.J.: Utilization of stem cells in alginate for nucleus pulposus tissue engineering. Tissue Eng. Part A. 20(5–6), 908–920 (2014)

    Article  Google Scholar 

  36. Huang, Y.C., Leung, V.Y., Lu, W.W., Luk, K.D.: Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J. Cell. Mol. Med. 12(6A), 2205–2216 (2008)

    Article  Google Scholar 

  37. Liang, C., Li, H., Tao, Y., Zhou, X., Li, F., Chen, G., Chen, Q.: Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc. J. Translational. Med. 10, 49–61 (2012)

    Article  Google Scholar 

  38. Potier, E., de Vries, S., van Doeselaar, M., Ito, K.: Potential application of notochordal cells for intervertebral disc regeneration: an in vitro assessment. Eur. Cell. Mater. 25, 68–80 (2014)

    Google Scholar 

  39. Shoukry, M., Li, J., Pei, M.: Reconstruction of an in vitro niche for the transition from intervertebral disc development to nucleus pulposus regeneration. Stem Cells Dev. 22(8), 1162–1176 (2013)

    Article  Google Scholar 

  40. Liu, Y., Fu, S., Rahaman, M.N., Mao, J.J., Bal, B.S.: Native nucleus pulposus tissue matrix promotes notochordal differentiation of human induced pluripotent stem cells with potential for treating intervertebral disc degeneration. J. Biomed. Mater. Res. A (2014). doi:10.1002/jbm.a.35243

    Google Scholar 

  41. Tao, Y.Q., Liang, C.Z., Li, H., Zhang, Y.J., Li, F.C., Chen, G., Chen, Q.X.: Potential of co-culture of nucleus pulposus mesenchymal stem cells and nucleus pulposus cells in hyperosmotic microenvironment for intervertebral disc regeneration. Cell Biol. Int. 37(8), 826–834 (2013)

    Article  Google Scholar 

  42. McCann, M.R., Bacher, C.A., Séguin, C.A.: Exploiting notochord cells for stem cell-based regeneration of the intervertebral disc. J. Cell Commun. Signal. 18, 39–43 (2011)

    Article  Google Scholar 

  43. Feng, G., Zhao, X., Liu, H., Zhang, H., Chen, X., Shi, R., Liu, X., Zhao, X., Zhang, W., Wang, B.: Transplantation of mesenchymal stem cells and nucleus pulposus cells in a degenerative disc model in rabbits: a comparison of 2 cell types as potential candidates for disc regeneration. J. Neurosurg. Spine 14(3), 322–329 (2011)

    Article  Google Scholar 

  44. Chen, S., Emery, S.E., Pei, M.: Coculture of synovium-derived stem cells and nucleus pulposus cells in serum-free defined medium with supplementation of transforming growth factor-beta1: a potential application of tissue-specific stem cells in disc regeneration. Spine(Phila Pa 1976) 34(12), 1272–1280 (2009)

    Article  Google Scholar 

  45. Ko, J.T., Lee, J.H., Kim, J.M., Kim, M.S., Rhee, J.M., Lee, H.B., Khang, G.: Development of biodegradable methoxy poly(ethyleneglycol)-polyesters diblock copolymers as drug carrier for implantable disc. Tissue Eng. Regen. Medicine. 3, 158–168 (2006)

    Google Scholar 

  46. Ko, Y.K., Kim, S.H., Ha, H.J., Yoon, S.J., Rhee, J.M., Kim, M.S., Lee, H.B., Khang, G.: Emerging trends in biological therapy for intervertebral disc degeneration. Key Eng. Mater. 342–343, 173–176 (2007)

    Article  Google Scholar 

  47. Bae, J.Y., Shin, Y.N., Hwang, J.H., Kim, E.Y., Yoo, H., Lee, D., Yoon, K.H., Khang, G.: Effect of purified alginate microcapsules on the regeneration of annulus fibrosus cells. Internat J. Tissue Regen. 2(3), 103–110 (2011)

    Google Scholar 

  48. Choi, J.H., Jang, J.W., Kim, S.H., Hong, H.K., Min, B.H., Son, Y., Rhee, J.M., Khang, G.: The effect of BMP-2 in DBP sponge for annulus fibrosus regeneration. Tissue Eng. Regen. Medicine. 5(4–6), 877–884 (2008)

    Google Scholar 

  49. Ha, H.J., Kim, S.H., Yoon, S.J., Park, S.W., So, J.W., Rhee, J.M., Kim, M.S., Khang, G., Lee, H.B.: Evaluation of various scaffolds for tissue engineered biodisc using annulus fibrcosus cells. Polymer (Korea) 32, 26–30 (2008)

    Google Scholar 

  50. Ko, Y.K., Kim, S.H., Jeong, J.S., Ha, H.J., Yoon, S.J., Rhee, J.M., Kim, K.S., Lee, H.B., Khang, G.: Biodisc tissue-engineered using PLGA/DBP hybrid scaffold. Polymer(Korea) 31, 14–19 (2007)

    Google Scholar 

  51. Ko, Y.K., Kim, S.H., Ha, H.J., Kim, M.S., Han, C.W., Rhee, J.M., Son, Y., Lee, H.B., Khang, G.: Tissue engineered biodisc using human intervertebral disc cells and PLGA/DBP scaffold. Tissue Eng. Regen. Medicine 4, 67–72 (2007)

    Google Scholar 

  52. Ko, Y.K., Jeong, J.S., Kim, S.H., Lim, J.Y., Rhee, J.M., Kim, M.S., Lee, H.B., Khang, G.: Effect of 2-D DBP/PLGA hybrid films on attachment and proliferation of intervertebral disc cells. Polymer(Korea) 32, 109–115 (2008)

    Google Scholar 

  53. Lim, J.Y., Kim, S.H., Park, S.W., So, J.W., Back, M.O., Kim, M.S., Khang, G., Rhee, J.M., Lee, H.B.: Regeneration of biodisc using annulus fibrosus and nucleus pulposus cell on PLGA/DBP hybrid scaffold. Tissue Eng. Regen. Medicine 5, 96–102 (2008)

    Google Scholar 

  54. Lee, S.K., Hong, H.K., Kim, S.J., Kim, Y.K., Song, Y.S., Ha, Y., Lee, D., Khang, G.: The comparison of sponges and PLGA scaffolds impregnated with DBP on growth behaviors of human intervertebral disc cells. Polymer(Korea) 34, 398–404 (2010)

    Google Scholar 

  55. Park, S.M., Kim, H.M., Kim, E.Y., Lee, H.G., Lee, C.J., Lee, D., Khang, G.: Influence of cell-based demineralized bone particle gels and sponges on nucleus pulposus therapy for intervertebral disc regeneration; In vivo study. Inter. J. Tissue Regen. 5, 96–102 (2013)

    Google Scholar 

  56. Jang, J.E., Kim, H.M., Song, J.E., Kee, D., Kwon, S.Y., Chung, J.W., Khang, G.: Regeneration of intervertebral disc using poly(lactic-co-glycolic acid) scaffolds included demineralized bone particle in vivo. Polymer(Korea) 37, 669–676 (2013)

    Google Scholar 

  57. So, J.W., Kim, S.H., Baek, M.O., Lim, J.Y., Roh, H.W., Lee, N.R., Kim, M.S., Ryu, G.H., Cho, Y.H., Lee, S.J., Min, B.H., Khang, G., Lee, H.B.: Effect of size of PLGA microsphere on proliferation and phenotype for human intervertebral disc cells. Tissue Eng. Regen. Medicine 4, 577–582 (2007)

    Google Scholar 

  58. Lee, J.H., Jang, J.W., So, J.W., Choi, J.H., Park, J.H., Ahn, S.I., Son, Y., Min, B.H., Khang, G.: Adhesion of human intervertebral disk cells on alginate/PLGA microspheres. Polymer(Korea) 33, 7–12 (2009)

    Google Scholar 

  59. So, J.W., Jang, J.W., Kim, S.H., Choi, J.H., Rhee, J.M., Min, B.H., Khang, G.: The effect of pore sizes on poly(L-lactide-co-glycolide) scaffolds for annulus fibrosus tissue regeneration. Polymer(Korea) 32, 516–522 (2008)

    Google Scholar 

  60. Kim, S.H., Choi, B.S., Ko, Y.K., Ha, H.J., Yoon, S.J., Rhee, J.M., Kim, M.S., Lee, H.B., Khang, G.: The characterization of PLGA/small intestinal submucosa composites as scaffolds for intervertebral disc. Key Eng. Mater. 342–343, 112–116 (2007)

    Google Scholar 

  61. Collier, J.P., Mayor, M.B., Jensen, R.E., Surprenant, V.A., Surprenant, H.P., McNamar, J.L. Belec, L.: Mechanisms of failure of modular prostheses. Clin. Orthop. Relat. Res., 129−39 (1992)

    Google Scholar 

  62. Shaban, M., Yoon, S.J., Ko, Y.K., Ha, H.J., Kim, S.H., So, J.W., Idrus, R.B.H., Khang, G.: Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold. J. Biomater. Sci. Polymer. Edn. 19, 1219–1237 (2008)

    Article  Google Scholar 

  63. Choi, J.H., Kim, S.H., Hong, H.K., Kim, S.J., Lee, S.K., Kim, O.Y., Park, J.H., Rhee, J.M., Khang, G.: Regeneration of biodisc using annulus fibrosus cell on hyaluronic acid loaded PLGA scaffold. Tissue Eng. Regen. Medicine 6, 83–88 (2009)

    Google Scholar 

  64. Jang, J.E., Kim, H.M., Song, J.E., Kee, D., Kwon, S.Y., Chung, J.W., Khang, G.: Regeneration of intervertebral disc using poly(lactic-co-glycolic acid) scaffolds included demineralized bone particle in vivo. Polymer(Korea) 37, 669–676 (2013)

    Google Scholar 

  65. Lee, S.K., Hong, H.K., Kim, S.J., Kim, Y.K., Lee, D., Khang, G.: Effects of laminated cylindrical scaffolds of keratin/poly(lactic-co-glycolic acid) hybrid film on annulus fibrous tissue regeneration. Polymer (Korea) 34, 474–479 (2010)

    Google Scholar 

  66. Hong, H.K., Lee, S.K., Song, Y.S., Kim, D.S., Eom, S., Kim, E.Y., Lee, D., Khang, G.: Biodisc regeneration using annulus fibrosus cell with hyaluronic acid impregnated small intestinal submucosa sponge. Polymer(Korea) 34, 282–288 (2010)

    Google Scholar 

  67. Ha, H.J., Kim, S.H., Yoon, S.J., Ko, Y.K., Lee, E.K., Son, Y., Kim, M.S., Rhee, J.M., Khang, G., Lee, H.B.: Characterization of annulus fibrosus and nucleus pulposus with sequential passage. Tissue Eng. Regen. Medicine 3, 416–422 (2006)

    Google Scholar 

  68. Kang, Y., Song, Y.S., Kim, E.Y., Oh, S.C., Song, J.E., Lee, D., Khang, G.: Differentiation of bone marrow stromal clls to nucleus pulposus cells by mixed co-culture. Intern. J. Tissue Regen. 3, 21–27 (2012)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gilson Khang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Khang, G., Song, J.E., Tripathy, N., Kim, E.Y., Lee, D. (2016). Recent Advances in Regenerative Approaches to Intervertebral Disc Degeneration. In: Jo, H., Jun, HW., Shin, J., Lee, S. (eds) Biomedical Engineering: Frontier Research and Converging Technologies. Biosystems & Biorobotics, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-21813-7_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-21813-7_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-21812-0

  • Online ISBN: 978-3-319-21813-7

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics