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Biomechanics in Annulus Fibrosus Degeneration and Regeneration

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Cutting-Edge Enabling Technologies for Regenerative Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1078))

Abstract

Degenerative disc degeneration (DDD) is the major cause of low back pain, which seriously affects the life of patients. Current surgical and conservative treatments only relieve the pain temporarily, yet fail to restore the normal biomechanics and functions of healthy spine. Indeed, high recurrence of disc herniation commonly happens after discectomy. Degenerative changes in biomechanical and structural properties of the intervertebral disc (IVD), including fissures in annulus fibrosus (AF) and volume loss of nucleus pulposus (NP), mainly contribute to DDD development. AF plays a critical role in the biomechanical properties of IVD as it structural integrity is essential to confine NP and maintain physiological intradiscal pressure under loading. Maintaining the homeostasis of AF and NP, and thereby IVD, requires regulation of their biomechanics, which is also involved in the onset and subsequent development of AF degeneration. Therefore, it is essential to understand the biomechanical changes of AF during degeneration, which can also provide valuable insights into the repair and regeneration of AF. In this review, we focus on the biomechanical properties of AF tissue associated with its homeostasis and degeneration, and discuss the biomechanical stimulus required for regeneration of AF. We also provide an overview of recent strategies to target and modulate cell mechanics toward AF regeneration.

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References

  1. Acaroglu ER, Iatridis JC et al (1995) Degeneration and aging affect the tensile behavior of human lumbar annulus fibrosus. Spine (Phila Pa 1976) 20(24):2690–2701

    Article  CAS  Google Scholar 

  2. Adams MA, Dolan P (2012) Intervertebral disc degeneration: evidence for two distinct phenotypes. J Anat 221(6):497–506

    Article  Google Scholar 

  3. Adams MA, McMillan DW et al (1996) Sustained loading generates stress concentrations in lumbar intervertebral discs. Spine (Phila Pa 1976) 21(4):434–438

    Article  CAS  Google Scholar 

  4. Adams MA, Freeman BJ et al (2000) Mechanical initiation of intervertebral disc degeneration. Spine (Phila Pa 1976) 25(13):1625–1636

    Article  CAS  Google Scholar 

  5. Adams MA, Dolan P et al (2009) The internal mechanical functioning of intervertebral discs and articular cartilage, and its relevance to matrix biology. Matrix Biol 28(7):384–389

    Article  CAS  Google Scholar 

  6. Andersson GB (1999) Epidemiological features of chronic low-back pain. Lancet 354(9178):581–585

    Article  CAS  Google Scholar 

  7. Bailey JF, Hargens AR et al (2014) Effect of microgravity on the biomechanical properties of lumbar and caudal intervertebral discs in mice. J Biomech 47(12):2983–2988

    Article  Google Scholar 

  8. Battie MC, Videman T et al (2009) The twin spine study: contributions to a changing view of disc degeneration. Spine J 9(1):47–59

    Article  Google Scholar 

  9. Beckstein JC, Sen S et al (2008) Comparison of animal discs used in disc research to human lumbar disc: axial compression mechanics and glycosaminoglycan content. Spine (Phila Pa 1976) 33(6):E166–E173

    Article  Google Scholar 

  10. Bhattacharjee M, Miot S et al (2012) Oriented lamellar silk fibrous scaffolds to drive cartilage matrix orientation: towards annulus fibrosus tissue engineering. Acta Biomater 8(9):3313–3325

    Article  CAS  Google Scholar 

  11. Blankenbaker DG, Haughton VM et al (2006) Axial rotation of the lumbar spinal motion segments correlated with concordant pain on discography: a preliminary study. AJR Am J Roentgenol 186(3):795–799

    Article  Google Scholar 

  12. Boubriak OA, Watson N et al (2013) Factors regulating viable cell density in the intervertebral disc: blood supply in relation to disc height. J Anat 222(3):341–348

    Article  Google Scholar 

  13. Bowles RD, Gebhard HH et al (2011) Tissue-engineered intervertebral discs produce new matrix, maintain disc height, and restore biomechanical function to the rodent spine. Proc Natl Acad Sci U S A 108(32):13106–13111

    Article  CAS  Google Scholar 

  14. Bruehlmann SB, Rattner JB et al (2002) Regional variations in the cellular matrix of the annulus fibrosus of the intervertebral disc. J Anat 201(2):159–171

    Article  Google Scholar 

  15. Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 20(11):1307–1314

    Article  CAS  Google Scholar 

  16. Chan SC, Ferguson SJ et al (2011) The effects of dynamic loading on the intervertebral disc. Eur Spine J 20(11):1796–1812

    Article  Google Scholar 

  17. Chen IR, Wei TS (2009) Disc height and lumbar index as independent predictors of degenerative spondylolisthesis in middle-aged women with low back pain. Spine (Phila Pa 1976) 34(13):1402–1409

    Article  Google Scholar 

  18. Cortes DH, Han WM et al (2013) Mechanical properties of the extra-fibrillar matrix of human annulus fibrosus are location and age dependent. J Orthop Res 31(11):1725–1732

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Court C, Chin JR et al (2007) Biological and mechanical consequences of transient intervertebral disc bending. Eur Spine J 16(11):1899–1906

    Article  Google Scholar 

  20. Doroski DM, Levenston ME et al (2010) Cyclic tensile culture promotes fibroblastic differentiation of marrow stromal cells encapsulated in poly(ethylene glycol)-based hydrogels. Tissue Eng Part A 16(11):3457–3466

    Article  CAS  Google Scholar 

  21. Driscoll TP, Nakasone RH et al (2013) Biaxial mechanics and inter-lamellar shearing of stem-cell seeded electrospun angle-ply laminates for annulus fibrosus tissue engineering. J Orthop Res 31(6):864–870

    Article  CAS  Google Scholar 

  22. Elliott DM, Sarver JJ (2004) Young investigator award winner: validation of the mouse and rat disc as mechanical models of the human lumbar disc. Spine (Phila Pa 1976) 29(7):713–722

    Article  Google Scholar 

  23. Elsaadany M, Winters K et al (2017) Equiaxial strain modulates adipose-derived stem cell differentiation within 3D biphasic scaffolds towards annulus fibrosus. Sci Rep 7:12868

    Article  Google Scholar 

  24. Engler AJ, Sen S et al (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689

    Article  CAS  Google Scholar 

  25. Finch P (2006) Technology insight: imaging of low back pain. Nat Clin Pract Rheumatol 2(10):554–561

    Article  Google Scholar 

  26. Guo QP, Liu C et al (2015) Gene expression modulation in TGF-3-mediated rabbit bone marrow stem cells using electrospun scaffolds of various stiffness. J Cell Mol Med 19(7):1582–1592

    Article  CAS  Google Scholar 

  27. Haglund L, Moir J et al (2011) Development of a bioreactor for axially loaded intervertebral disc organ culture. Tissue Eng Part C Methods 17(10):1011–1019

    Article  CAS  Google Scholar 

  28. Holguin N, Uzer G et al (2011) Brief daily exposure to low-intensity vibration mitigates the degradation of the intervertebral disc in a frequency-specific manner. J Appl Physiol (1985) 111(6):1846–1853

    Article  Google Scholar 

  29. Holguin N, Martin JT et al (2013) Low-intensity vibrations partially maintain intervertebral disc mechanics and spinal muscle area during deconditioning. Spine J 13(4):428–436

    Article  Google Scholar 

  30. Holzapfel GA, Schulze-Bauer CA et al (2005) Single lamellar mechanics of the human lumbar annulus fibrosus. Biomech Model Mechanobiol 3(3):125–140

    Article  CAS  Google Scholar 

  31. Hsieh AH, Twomey JD (2010) Cellular mechanobiology of the intervertebral disc: new directions and approaches. J Biomech 43(1):137–145

    Article  Google Scholar 

  32. Hudson KD, Alimi M et al (2013) Recent advances in biological therapies for disc degeneration: tissue engineering of the annulus fibrosus, nucleus pulposus and whole intervertebral discs. Curr Opin Biotechnol 24(5):872–879

    Article  CAS  Google Scholar 

  33. Iatridis JC, Setton LA et al (1998) Degeneration affects the anisotropic and nonlinear behaviors of human annulus fibrosus in compression. J Biomech 31(6):535–544

    Article  CAS  Google Scholar 

  34. Iatridis JC, MacLean JJ et al (2006) Effects of mechanical loading on intervertebral disc metabolism in vivo. J Bone Joint Surg Am 88(Suppl 2):41–46

    PubMed  PubMed Central  Google Scholar 

  35. Iatridis JC, Nicoll SB et al (2013) Role of biomechanics in intervertebral disc degeneration and regenerative therapies: what needs repairing in the disc and what are promising biomaterials for its repair? Spine J 13(3):243–262

    Article  Google Scholar 

  36. Ivanovska IL, Shin JW et al (2015) Stem cell mechanobiology: diverse lessons from bone marrow. Trends Cell Biol 25(9):523–532

    Article  Google Scholar 

  37. Khetan S, Guvendiren M et al (2013) Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat Mater 12(5):458–465

    Article  CAS  Google Scholar 

  38. Kim J, Yang SJ et al (2012) Effect of shear force on intervertebral disc (IVD) degeneration: an in vivo rat study. Ann Biomed Eng 40(9):1996–2004

    Article  Google Scholar 

  39. Korecki CL, MacLean JJ et al (2008) Dynamic compression effects on intervertebral disc mechanics and biology. Spine (Phila Pa 1976) 33(13):1403–1409

    Article  Google Scholar 

  40. Kroeber MW, Unglaub F 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):2684–2690

    Article  Google Scholar 

  41. Lacroix D, Prendergast PJ (2002) A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J Biomech 35(9):1163–1171

    Article  CAS  Google Scholar 

  42. Lambeek LC, van Tulder MW et al (2011) The trend in total cost of back pain in The Netherlands in the period 2002 to 2007. Spine (Phila Pa 1976) 36(13):1050–1058

    Article  Google Scholar 

  43. Le Maitre CL, Freemont AJ et al (2005) The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther 7(4):R732–R745

    Article  Google Scholar 

  44. Le Maitre CL, Frain J et al (2008) Human cells derived from degenerate intervertebral discs respond differently to those derived from non-degenerate intervertebral discs following application of dynamic hydrostatic pressure. Biorheology 45(5):563–575

    PubMed  Google Scholar 

  45. Li B, Wang JH (2010) Application of sensing techniques to cellular force measurement. Sensors (Basel) 10(11):9948–9962

    Article  Google Scholar 

  46. Li J, Wang J et al (2012) The influence of delayed compressive stress on TGF-beta1-induced chondrogenic differentiation of rat BMSCs through Smad-dependent and Smad-independent pathways. Biomaterials 33(33):8395–8405

    Article  CAS  Google Scholar 

  47. Li J, Liu C et al (2014) Regional variations in the cellular, biochemical, and biomechanical characteristics of rabbit annulus fibrosus. PLoS One 9(3):e91799

    Article  Google Scholar 

  48. Li B, Li J et al (2017) Annulus fibrosus tissue engineering: achievements and future development. In: Khang G (ed) Handbook of intelligent scaffolds for tissue engineering and regenerative medicine, 2nd edn. Pan Stanford Publishing, Singapore, pp 1029–1069

    Google Scholar 

  49. Liu GZ, Ishihara H et al (2001) Nitric oxide mediates the change of proteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure. Spine (Phila Pa 1976) 26(2):134–141

    Article  CAS  Google Scholar 

  50. Liu C, Guo Q et al (2014) Identification of rabbit annulus fibrosus-derived stem cells. PLoS One 9(9):e108239

    Article  Google Scholar 

  51. Liu C, Zhu C et al (2015) The effect of the fibre orientation of electrospun scaffolds on the matrix production of rabbit annulus fibrosus-derived stem cells. Bone Res 3:15012

    Article  Google Scholar 

  52. Martin JT, Milby AH et al (2014) Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model. Acta Biomater 10(6):2473–2481

    Article  CAS  Google Scholar 

  53. Mizuno H, Roy AK et al (2004) Tissue-engineered composites of annulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine (Phila Pa 1976) 29(12):1290–1297 discussion 1297-1298

    Article  Google Scholar 

  54. Mok FP, Samartzis D et al (2010) ISSLS prize winner: prevalence, determinants, and association of Schmorl nodes of the lumbar spine with disc degeneration: a population-based study of 2449 individuals. Spine (Phila Pa 1976) 35(21):1944–1952

    Article  Google Scholar 

  55. Moraes C, Sun Y et al (2011) (Micro)managing the mechanical microenvironment. Integr Biol (Camb) 3(10):959–971

    Article  Google Scholar 

  56. Murray CJ, Vos T et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 380(9859):2197–2223

    Article  Google Scholar 

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

    Article  Google Scholar 

  58. Nerurkar NL, Baker BM et al (2009) Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus. Nat Mater 8(12):986–992

    Article  CAS  Google Scholar 

  59. Nerurkar NL, Sen S et al (2011) Dynamic culture enhances stem cell infiltration and modulates extracellular matrix production on aligned electrospun nanofibrous scaffolds. Acta Biomater 7(2):485–491

    Article  CAS  Google Scholar 

  60. Paul CP, Zuiderbaan HA et al (2012) Simulated-physiological loading conditions preserve biological and mechanical properties of caprine lumbar intervertebral discs in ex vivo culture. PLoS One 7(3):e33147

    Article  CAS  Google Scholar 

  61. Purmessur D, Walter BA et al (2013) A role for TNFalpha in intervertebral disc degeneration: a non-recoverable catabolic shift. Biochem Biophys Res Commun 433(1):151–156

    Article  CAS  Google Scholar 

  62. Roy TC, Lopez HP et al (2013) Loads worn by soldiers predict episodes of low back pain during deployment to Afghanistan. Spine (Phila Pa 1976) 38(15):1310–1317

    Article  Google Scholar 

  63. Sayson JV, Hargens AR (2008) Pathophysiology of low back pain during exposure to microgravity. Aviat Space Environ Med 79(4):365–373

    Article  Google Scholar 

  64. Setton LA, Chen J (2004) Cell mechanics and mechanobiology in the intervertebral disc. Spine (Phila Pa 1976) 29(23):2710–2723

    Article  Google Scholar 

  65. Smith RL, Carter DR et al (2004) Pressure and shear differentially alter human articular chondrocyte metabolism: a review. Clin Orthop Relat Res 427(Suppl):S89–S95

    Google Scholar 

  66. Stefanakis M, Luo J et al (2014) ISSLS prize winner: mechanical influences in progressive intervertebral disc degeneration. Spine (Phila Pa 1976) 39(17):1365–1372

    Article  Google Scholar 

  67. Taunton JE, Ryan MB et al (2002) A retrospective case-control analysis of 2002 running injuries. Br J Sports Med 36(2):95–101

    Article  CAS  Google Scholar 

  68. Urban JP (2002) The role of the physicochemical environment in determining disc cell behaviour. Biochem Soc Trans 30(Pt 6):858–864

    Article  CAS  Google Scholar 

  69. Urban JP, Smith S et al (2004) Nutrition of the intervertebral disc. Spine (Phila Pa 1976) 29(23):2700–2709

    Article  Google Scholar 

  70. van der Meulen MC, Huiskes R (2002) Why mechanobiology? A survey article. J Biomech 35(4):401–414

    Article  Google Scholar 

  71. Vergroesen PP, van der Veen AJ et al (2014) Intradiscal pressure depends on recent loading and correlates with disc height and compressive stiffness. Eur Spine J 23(11):2359–2368

    Article  Google Scholar 

  72. Wan Y, Feng G et al (2008) Biphasic scaffold for annulus fibrosus tissue regeneration. Biomaterials 29(6):643–652

    Article  CAS  Google Scholar 

  73. Wang DL, Jiang SD et al (2007) Biologic response of the intervertebral disc to static and dynamic compression in vitro. Spine (Phila Pa 1976) 32(23):2521–2528

    Article  Google Scholar 

  74. Wilke HJ, Neef P et al (1999) New in vivo measurements of pressures in the intervertebral disc in daily life. Spine (Phila Pa 1976) 24(8):755–762

    Article  CAS  Google Scholar 

  75. Wismer N, Grad S et al (2014) Biodegradable electrospun scaffolds for annulus fibrosus tissue engineering: effect of scaffold structure and composition on annulus fibrosus cells in vitro. Tissue Eng Part A 20(3–4):672–682

    CAS  PubMed  Google Scholar 

  76. Yeganegi M, Kandel RA et al (2010) Characterization of a biodegradable electrospun polyurethane nanofiber scaffold: mechanical properties and cytotoxicity. Acta Biomater 6(10):3847–3855

    Article  CAS  Google Scholar 

  77. Yurube T, Takada T et al (2012) Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration. Arthritis Res Ther 14(2):R51

    Article  CAS  Google Scholar 

  78. Zhang YH, Zhao CQ et al (2011) Substrate stiffness regulates apoptosis and the mRNA expression of extracellular matrix regulatory genes in the rat annular cells. Matrix Biol 30(2):135–144

    Article  Google Scholar 

  79. Zhu C, Li J et al (2016) Modulation of the gene expression of annulus fibrosus-derived stem cells using poly(ether carbonate urethane)urea scaffolds of tunable elasticity. Acta Biomater 29:228–238

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Key R&D Program of China (2016YFC1100203), National Natural Science Foundation of China (81672213 and 31530024), Jiangsu Provincial Special Program of Medical Science (BL2012004), Jiangsu Provincial Clinical Orthopedic Center, Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, and Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_2529).

Conflict of Interests

The authors declare that there is no conflict of interest regarding the publication of this paper.

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  1. Author contributed equally with all other contributors.Genglei Chu and Chen Shi

Authors and Affiliations

  1. Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China

    Genglei Chu, Huan Wang, Huilin Yang & Bin Li

  2. Department of Orthopaedic Surgery, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China

    Genglei Chu, Jun Lin, Shenghao Wang, Huan Wang, Tao Liu, Huilin Yang & Bin Li

  3. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

    Chen Shi

  4. China Orthopaedic Regenerative Medicine Group (CORMed), Hangzhou, Zhejiang, China

    Bin Li

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  1. Genglei Chu
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  3. Jun Lin
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  4. Shenghao Wang
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  5. Huan Wang
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  6. Tao Liu
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Correspondence to Bin Li .

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Editors and Affiliations

  1. The Catholic University of Korea, Seoul, Korea (Republic of)

    Heung Jae Chun

  2. Hallym University, Gangwon-do, Korea (Republic of)

    Chan Hum Park

  3. Kyung Hee University, Seoul, Korea (Republic of)

    Il Keun Kwon

  4. Chonbuk National University, Jeonju, Korea (Republic of)

    Gilson Khang

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Chu, G. et al. (2018). Biomechanics in Annulus Fibrosus Degeneration and Regeneration. In: Chun, H., Park, C., Kwon, I., Khang, G. (eds) Cutting-Edge Enabling Technologies for Regenerative Medicine. Advances in Experimental Medicine and Biology, vol 1078. Springer, Singapore. https://doi.org/10.1007/978-981-13-0950-2_21

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