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Enhancement of Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Devices

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Abstract

Insufficient nutrient supply has been suggested to be one of the etiologies for intervertebral disc (IVD) degeneration. We are investigating nutrient transport into the IVD as a potential treatment strategy for disc degeneration. Most cellular activities in the IVD (e.g., cell proliferation and extracellular matrix production) are mainly driven by adenosine-5′-triphosphate (ATP) which is the main energy currency. The objective of this study was to investigate the effect of increased mass transfer on ATP production in the IVD by the implantation of polyurethane (PU) mass transfer devices. In this study, the porcine functional spine units were used and divided into intact, device and surgical groups. For the device and surgical groups, two puncture holes were created bilaterally at the dorsal side of the annulus fibrosus (AF) region and the PU mass transfer devices were only implanted into the holes in the device group. Surgical groups were observed for the effects of placing the holes through the AF only. After 7 days of culture, the surgical group exhibited a significant reduction in the compressive stiffness and disc height compared to the intact and device groups, whereas no significant differences were found in compressive stiffness, disc height and cell viability between the intact and device groups. ATP, lactate and the proteoglycan contents in the device group were significantly higher than the intact group. These results indicated that the implantation of the PU mass transfer device can promote the nutrient transport and enhance energy production without compromising mechanical and cellular functions in the disc. These results also suggested that compromise to the AF has a negative impact on the IVD and must be addressed when treatment strategies are considered. The results of this study will help guide the development of potential strategies for disc degeneration.

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References

  1. Acosta, F. L., L. Metz, H. D. Adkisson, J. Liu, E. Carruthers-Liebenberg, C. Milliman, M. Maloney, and J. C. Lotz. Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells. Tissue Eng. Pt. A 17(23–24):3045–3055, 2011.

    Article  CAS  Google Scholar 

  2. Adams, M. A., and P. J. Roughley. What is intervertebral disc degeneration, and what causes it? Spine 31(18):2151–2161, 2006.

    Article  PubMed  Google Scholar 

  3. An, H. S., P. A. Anderson, V. M. Haughton, J. C. Iatridis, J. D. Kang, J. C. Lotz, R. N. Natarajan, T. R. Oegema, Jr, P. Roughley, L. A. Setton, J. P. Urban, T. Videman, G. B. Andersson, and J. N. Weinstein. Introduction: disc degeneration: summary. Spine (Phila Pa 1976) 29(23):2677–2678, 2004.

    Article  Google Scholar 

  4. Andersson, G. B. J. Epidemiological features of chronic low-back pain. Lancet 354(9178):581–585, 1999.

    Article  CAS  PubMed  Google Scholar 

  5. Bibby, S. R., D. A. Jones, R. M. Ripley, and J. P. Urban. Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells. Spine (Phila Pa 1976) 30(5):487–496, 2005.

    Article  Google Scholar 

  6. Bibby, S. R. S., D. A. Jones, R. M. Ripley, and J. P. G. Urban. Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells. Spine 30(5):487–496, 2005.

    Article  PubMed  Google Scholar 

  7. Boubriak, O. A., N. Watson, S. S. Sivan, N. Stubbens, and J. P. Urban. Factors regulating viable cell density in the intervertebral disc: blood supply in relation to disc height. J. Anat. 222(3):341–348, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bron, J. L., A. J. van der Veen, M. N. Helder, B. J. van Royen, T. H. Smit, S. T. E. G. Amsterdam, and R. I. Move. Biomechanical and in vivo evaluation of experimental closure devices of the annulus fibrosus designed for a goat nucleus replacement model. Eur. Spine J. 19(8):1347–1355, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Burnstock, G. The past, present and future of purine nucleotides as signalling molecules. Neuropharmacology 36(9):1127–1139, 1997.

    Article  CAS  PubMed  Google Scholar 

  10. Chida, J., K. Yamane, T. Takei, and H. Kido. An efficient extraction method for quantitation of adenosine triphosphate in mammalian tissues and cells. Anal. Chim. Acta 727:8–12, 2012.

    Article  CAS  PubMed  Google Scholar 

  11. Croucher, L. J., A. Crawford, P. V. Hatton, R. G. G. Russell, and D. J. Buttle. Extracellular ATP and UTP stimulate cartilage proteoglycan and collagen accumulation in bovine articular chondrocyte pellet cultures. Bba-Mol. Basis Dis. 1502(2):297–306, 2000.

    Article  CAS  Google Scholar 

  12. Drazin, D., J. Rosner, P. Avalos, and F. Acosta. Stem cell therapy for degenerative disc disease. Adv. Orthop. 2012:961052, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Elliott, D. M., C. S. Yerramalli, J. C. Beckstein, J. I. Boxberger, W. Johannessen, and E. J. Vresilovic. The effect of relative needle diameter in puncture and sham injection animal models of degeneration. Spine (Phila Pa 1976) 33(6):588–596, 2008.

    Article  Google Scholar 

  14. Feng, G. J., X. F. Zhao, H. Liu, H. N. Zhang, X. J. Chen, R. Shi, X. Liu, X. D. Zhao, W. L. Zhang, and B. Y. Wang. 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 laboratory investigation. J. Neurosurg.Spine 14(3):322–329, 2011.

    Article  PubMed  Google Scholar 

  15. Fernando, H. N., J. Czamanski, T. Y. Yuan, W. Gu, A. Salahadin, and C. Y. Huang. Mechanical loading affects the energy metabolism of intervertebral disc cells. J. Orthop. Res. 29(11):1634–1641, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gawri, R., F. Mwale, J. Ouellet, P. J. Roughley, T. Steffen, J. Antoniou, and L. Haglund. Development of an organ culture system for Long-Term survival of the intact human intervertebral disc. Spine 36(22):1835–1842, 2011.

    Article  PubMed  Google Scholar 

  17. Gilson, A., M. Dreger, and J. P. G. Urban. Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers. Arthritis Res. Ther. 12(1):R24, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gonzales, S., B. Rodriguez, C. Barrera, and C. Y. C. Huang. Measurement of ATP-induced membrane potential changes in IVD cells. Cell. Mol. Bioeng. 7(4):598–606, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gonzales, S., C. Wang, H. Levene, H. S. Cheung, and C. Y. C. Huang. ATP promotes extracellular matrix biosynthesis of intervertebral disc cells. Cell Tissue Res. 359(2):635–642, 2015.

    Article  CAS  PubMed  Google Scholar 

  20. Grunhagen, T., A. Shirazi-Adl, J. C. Fairbank, and J. P. Urban. Intervertebral disk nutrition: a review of factors influencing concentrations of nutrients and metabolites. Orthop. Clin. North Am. 42(4):465–477, 2011.

    Article  PubMed  Google Scholar 

  21. Grunhagen, T., G. Wilde, D. M. Soukane, S. A. Shirazi-Adl, and J. P. Urban. Nutrient supply and intervertebral disc metabolism. J. Bone Joint Surg. Am. 88(Suppl 2):30–35, 2006.

    PubMed  Google Scholar 

  22. Gu, W. Y., and H. Yao. Effects of hydration and fixed charge density on fluid transport in charged hydrated soft tissues. Ann. Biomed. Eng. 31(10):1162–1170, 2003.

    Article  PubMed  Google Scholar 

  23. Guehring, T., G. Wilde, M. Sumner, T. Grunhagen, G. B. Karney, U. K. Tirlapur, and J. P. G. Urban. Notochordal intervertebral disc cells sensitivity to nutrient deprivation. Arthritis Rheum. 60(4):1026–1034, 2009.

    Article  PubMed  Google Scholar 

  24. Henriksson, H. B., T. Svanvik, M. Jonsson, M. Hagman, M. Horn, A. Lindahl, and H. Brisby. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine 34(2):141–148, 2009.

    Article  PubMed  Google Scholar 

  25. Hirschberg, C. B., P. W. Robbins, and C. Abeijon. Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. Annu. Rev. Biochem. 67:49–69, 1998.

    Article  CAS  PubMed  Google Scholar 

  26. Horner, H. A., and J. P. G. Urban. 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 26(23):2543–2549, 2001.

    Article  CAS  PubMed  Google Scholar 

  27. Hsieh, A. H., D. Hwang, D. A. Ryan, A. K. Freeman, and H. Kim. Degenerative anular changes induced by puncture are associated with insufficiency of disc biomechanical function. Spine 34(10):998–1005, 2009.

    Article  PubMed  Google Scholar 

  28. Huang, C. Y. C., M. A. Deitzer, and H. S. Cheung. Effects of fibrinolytic inhibitors on chondrogenesis of bone-marrow derived mesenchymal stem cells in fibrin gels. Biomech. Model. Mechan. 6(1–2):5–11, 2007.

    Article  Google Scholar 

  29. Huang, C. Y., and W. Y. Gu. Effects of mechanical compression on metabolism and distribution of oxygen and lactate in intervertebral disc. J. Biomech. 41(6):1184–1196, 2008.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Huang, Y. C., J. P. G. Urban, and K. D. K. Luk. Opinion intervertebral disc regeneration: do nutrients lead the way? Nat. Rev. Rheumatol. 10(9):561–566, 2014.

    Article  PubMed  Google Scholar 

  31. Jackson, A., and W. Gu. Transport Properties of Cartilaginous Tissues. Curr. Rheumatol. Rev. 5(1):40, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jackson, A. R., C. Y. Huang, and W. Y. Gu. Effect of endplate calcification and mechanical deformation on the distribution of glucose in intervertebral disc: a 3D finite element study. Comput. Method Biomec. 14(2):195–204, 2011.

    Article  Google Scholar 

  33. Johnson, K., A. Jung, A. Murphy, A. Andreyev, J. Dykens, and R. Terkeltaub. Mitochondrial oxidative phosphorylation is a downstream regulator of nitric oxide effects on chondrocyte matrix synthesis and mineralization. Arthritis Rheum. 43(7):1560–1570, 2000.

    Article  CAS  PubMed  Google Scholar 

  34. Johnson, S., and P. Rabinovitch. Ex vivo imaging of excised tissue using vital dyes and confocal microscopy. Curr. Protoc. Cytom. 9:9–39, 2012.

    Google Scholar 

  35. Johnson, K., C. I. Svensson, D. Van Etten, S. S. Ghosh, A. N. Murphy, H. C. Powell, and R. Terkeltaub. Mediation of spontaneous knee osteoarthritis by progressive chondrocyte ATP depletion in Hartley guinea pigs. Arthritis Rheum. 50(4):1216–1225, 2004.

    Article  CAS  PubMed  Google Scholar 

  36. Katz, J. N. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J. Bone Joint Surg. Am. 88a:21–24, 2006.

    Google Scholar 

  37. Korecki, C. L., J. J. Costi, and J. C. Iatridis. Needle puncture injury affects intervertebral disc mechanics and biology in an organ culture model. Spine 33(3):235–241, 2008.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Levene, H. B. Analysis of Tyrosine-Derived Novel Synthetic Polymer Scaffold Devices for Guided Tissue Regeneration, Rutgers University and the University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, 1999, p. 167.

  39. Likhitpanichkul, M., M. Dreischarf, S. Illien-Junger, B. A. Walter, T. Nukaga, R. G. Long, D. Sakai, A. C. Hecht, and J. C. Iatridis. Fibrin-genipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, situ biomechanics, and in vivo degradation tests. Eur. Cells Mater. 28:25–38, 2014.

    Article  CAS  Google Scholar 

  40. Long, R. G., S. G. Rotman, W. W. Hom, D. J. Assael, D. W. Grijpma, and J. C. Iatridis. In vitro and biomechanical screening of polyethylene glycol and poly(trimethylene carbonate) block copolymers for annulus fibrosus repair, J. Tissue Eng. Regen. Med. 2016.

  41. Long, R. G., O. M. Torre, W. W. Hom, D. J. Assael, and J. C. Iatridis. Design requirements for annulus fibrosus repair: review of forces, displacements, and material properties of the intervertebral disk and a summary of candidate hydrogels for repair. J. Biomech. Eng. 138(2):021007, 2016.

    Article  PubMed  Google Scholar 

  42. MacLean, J. J., C. R. Lee, S. Grad, K. Ito, M. Alini, and J. C. Iatridis. Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo. Spine 28(10):973–981, 2003.

    PubMed  Google Scholar 

  43. Martin, J. A., A. Martini, A. Molinari, W. Morgan, W. Ramalingam, J. A. Buckwalter, and T. O. McKinley. Mitochondrial electron transport and glycolysis are coupled in articular cartilage. Osteoarthr. Cartilage 20(4):323–329, 2012.

    Article  CAS  Google Scholar 

  44. Masuda, K., T. R. Oegema, and H. S. An. Growth factors and treatment of intervertebral disc degeneration. Spine 29(23):2757–2769, 2004.

    Article  PubMed  Google Scholar 

  45. Michalek, A. J., M. R. Buckley, L. J. Bonassar, I. Cohen, and J. C. Iatridis. The effects of needle puncture injury on microscale shear strain in the intervertebral disc annulus fibrosus. Spine J. 10(12):1098–1105, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Neidlinger-Wilke, C., A. Mietsch, C. Rinkler, H. J. Wilke, A. Ignatius, and J. Urban. Interactions of environmental conditions and mechanical loads have influence on matrix turnover by nucleus pulposus cells. J. Orthop. Res. 30(1):112–121, 2012.

    Article  PubMed  Google Scholar 

  47. Osada, R., H. Ohshima, H. Ishihara, K. Yudoh, K. Sakai, H. Matsui, and H. Tsuji. 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. Orthopaed. Res. 14(5):690–699, 1996.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pratsinis, H., and D. Kletsas. 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(11):1858–1866, 2007.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Prydz, K., and K. T. Dalen. Synthesis and sorting of proteoglycans—commentary. J. Cell. Sci. 113(2):193–205, 2000.

    CAS  PubMed  Google Scholar 

  51. Schmidt, H., A. Shirazi-Adl, F. Galbusera, and H. J. Wilke. Response analysis of the lumbar spine during regular daily activities–a finite element analysis. J. Biomech. 43(10):1849–1856, 2010.

    Article  PubMed  Google Scholar 

  52. Smith, L. J., N. L. Nerurkar, K. S. Choi, B. D. Harfe, and D. M. Elliott. Degeneration and regeneration of the intervertebral disc: lessons from development. Dis. Model Mech. 4(1):31–41, 2011.

    Article  PubMed  Google Scholar 

  53. Sobajima, S., J. F. Kompel, J. S. Kim, C. J. Wallach, D. D. Robertson, M. T. Vogt, J. D. Kang, and L. G. Gilbertson. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine 30(1):15–24, 2005.

    Article  PubMed  Google Scholar 

  54. Urban, J. P. G., and S. Roberts. Degeneration of the intervertebral disc. Arthritis Res. Ther. 5(3):120–130, 2003.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Urban, J. P. G., S. Smith, and J. C. T. Fairbank. Nutrition of the intervertebral disc. Spine 29(23):2700–2709, 2004.

    Article  PubMed  Google Scholar 

  56. Waldman, S. D., J. Usprech, L. E. Flynn, and A. A. Khan. Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs. Osteoarthr. Cartilage 18(6):864–872, 2010.

    Article  CAS  Google Scholar 

  57. Walter, B. A., C. L. Korecki, D. Purmessur, P. J. Roughley, A. J. Michalek, and J. C. Iatridis. Complex loading affects intervertebral disc mechanics and biology. Osteoarthr. Cartilage 19(8):1011–1018, 2011.

    Article  CAS  Google Scholar 

  58. Wang, Y. F., C. M. Barrera, E. A. Dauer, W. Gu, F. Andreopoulos, and C. C. Huang. Systematic characterization of porosity and mass transport and mechanical properties of porous polyurethane scaffolds. J. Mech. Behav. Biomed. Mater. 65:657–664, 2016.

    Article  PubMed  Google Scholar 

  59. Wang, C., S. Gonzales, H. Levene, W. Y. Gu, and C. Y. C. Huang. Energy metabolism of intervertebral disc under mechanical loading. J. Orthopaed. Res. 31(11):1733–1738, 2013.

    CAS  Google Scholar 

  60. Wang, D. L., S. D. Jiang, and L. Y. Dai. Biologic response of the intervertebral disc to static and dynamic compression in vitro. Spine (Phila Pa 1976) 32(23):2521–2528, 2007.

    Article  Google Scholar 

  61. Wu, Y. R., S. Cisewski, B. L. Sachs, and H. Yao. Effect of cartilage endplate on cell based disc regeneration: a finite element analysis. Mol. Cell. Biomech. 10(2):159–182, 2013.

    PubMed  PubMed Central  Google Scholar 

  62. Yao, H., M. A. Justiz, D. Flagler, and W. Y. Gu. Effects of swelling pressure and hydraulic permeability on dynamic compressive behavior of lumbar annulus fibrosus. Ann. Biomed. Eng. 30(10):1234–1241, 2002.

    Article  PubMed  Google Scholar 

  63. Zhou, S., Z. Cui, and J. P. Urban. Nutrient gradients in engineered cartilage: metabolic kinetics measurement and mass transfer modeling. Biotechnol. Bioeng. 101(2):408–421, 2008.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Grant AR066240 from the NIH and the University of Miami Provost’s Research Award.

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Authors and Affiliations

  1. Department of Biomedical Engineering, College of Engineering, University of Miami, 1251 Memorial Dr #219, Coral Gables, FL, 33146, USA

    Yu-Fu Wang & C. -Y. Charles Huang

  2. Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Howard B. Levene

  3. Department of Mechanical and Aerospace Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA

    Weiyong Gu

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  1. Yu-Fu Wang
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Correspondence to C. -Y. Charles Huang.

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Associate Editor Peter E. McHugh oversaw the review of this article.

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Wang, YF., Levene, H.B., Gu, W. et al. Enhancement of Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Devices. Ann Biomed Eng 45, 2098–2108 (2017). https://doi.org/10.1007/s10439-017-1867-8

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