Intervertebral disc degeneration: an experimental and numerical study using a rabbit model
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Animal models have been extensively used for the study of degenerative diseases and evaluation of new therapies to stop or even reverse the disease progression. The aim of this study is to reproduce lumbar intervertebral disc degeneration in a rabbit model by performing a percutaneous annular puncture at L4L5 level. The effect of this damage on the spine behaviour was analysed combining three different techniques: imaging processing, mechanical testing and computational modelling. Twenty New Zealand white rabbits were divided into control and experimental groups and followed up during 6 months. Intervertebral disc height, as well as nucleus area and signal intensity, decreased with degeneration while storage and loss moduli increased. Both changes may be related to the loss of water and tissue fibrosis. Similar but slighter changes were reported for adjacent discs. A finite element model was built based on MRI and mechanical testing findings to add new biomechanical information that cannot be obtained experimentally. Four stages were computationally simulated representing the different experimental phases. The numerical simulations showed that compressive stresses in the damaged and adjacent discs were modified with the progression of degeneration. Although extrapolation to humans should be carefully made, the use of numerical animal models combined with an experimental one could give a new insight of the overall mechanical behaviour of the spine.
KeywordsAnimal model Intervertebral disc degeneration Finite element model Experimental Lumbar spine
This work was supported by the Spanish Ministry of Economy and Competitiveness through projects DPI 2016-79302-R and by the Spanish Ministry of Education, Culture and Sports (Grant FPU13/01070).
Compliance with ethical standards
Conflict of interest
No conflict of interest should be declared by any of the authors.
This study was carried out in strict accordance with the recommendations in the Royal Decree 1201/2005 of 10 October 2005 (BOE from Oct. 21) on protection of animals used for experimentation and other scientific purposes. Experimental protocols were approved by the Committee on the Ethics of Animal Experiments of Minimally Invasive Surgery Centre Jesús Usón and by the Council of Agriculture and Rural Development of the Regional Government of Extremadura, Spain.
- 2.Vo N, Niedernhofer LJ, Nasto LA, Jacobs L, Robbins PD, Kang J et al (2013) An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints. J Orthop Res 31:831–837. https://doi.org/10.1002/jor.22204 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Osti OL, Vernon-Roberts B, Fraser RD (1990) 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine (Phila Pa 1976) 15:762–767Google Scholar
- 7.Reitmaier S, Schuelke J, Schmidt H, Volkheimer D, Ignatius A, Wilke HJ (2017) Spinal fusion without instrumentation—experimental animal study. Clin Biomech 46:6–14. https://doi.org/10.1016/j.clinbiomech.2017.04.008. CrossRefGoogle Scholar
- 10.Anderson GD, Li X, Tannoury T, Beck G, Balian GA (2003) Fibronectin fragment stimulates intervertebral disc degeneration in vivo. Spine (Phila Pa 1976) 28:2338–2345. https://doi.org/10.1097/01.BRS.0000096943.27853.BC. CrossRefGoogle Scholar
- 11.Kroeber MW, Unglaub F, Wang H, Schmid C, Thomsen M, Nerlich A 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) 27:2684–2690. https://doi.org/10.1097/00007632-200212010-00007. CrossRefGoogle Scholar
- 20.Leckie SK, Bechara BP, Hartman RA, Sowa GA, Woods BI, Coelho JP et al (2012) Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model. Spine J 12:7–20. https://doi.org/10.1016/j.spinee.2011.09.011 CrossRefPubMedGoogle Scholar
- 21.Gullbrand SE, Ashinsky BG, Martin JT, Pickup S, Smith LJ, Mauck RL et al (2016) Correlations between quantitative T2 and T1p MRI, mechanical properties and biochemical composition in a rabbit lumbar intervertebral disc degeneration model. J Orthop Res 34(8):1382. https://doi.org/10.1002/jor.23269 CrossRefPubMedGoogle Scholar
- 22.Hartman RA, Bell KM, Quan B, Nuzhao Y, Sowa GA, Kang JD (2015) Needle puncture in rabbit functional spinal units alters rotational biomechanics. J Spinal Disord Tech 28:E146–E153. https://doi.org/10.1161/CIRCRESAHA.116.303790.The. CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Beckstein JC, Sen S, Schaer TP, Vresilovic EJ, Elliott DM (2008) Comparison of animal discs used in disc research to human lumbar disc: torsion mechanics and collagen content. Spine (Phila Pa 1976) 33:E166–E173. https://doi.org/10.1097/BRS.0b013e31824d911c.Comparison. CrossRefGoogle Scholar
- 29.Meyers M, Chawla K (1998) Mechanical behavior of materials. Cambridge University Press, CambridgeGoogle Scholar
- 33.Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976) 31:2151–2161. https://doi.org/10.1097/01.brs.0000231761.73859.2c. CrossRefGoogle Scholar
- 35.Inoue N, Espinoza Orias A (2011) Biomechanics of intervertebral disc degeneration. Orthop Clin N Am 42:487–499. https://doi.org/10.1016/j.ocl.2011.07.001.Biomechanics. CrossRefGoogle Scholar
- 36.Zhou Z, Gao M, Wei F, Liang J, Deng W, Dai X et al (2014) Shock absorbing function study on denucleated intervertebral disc with or without hydrogel injection through static and dynamic biomechanical tests in vitro. Biomed Res Int 2014. https://doi.org/10.1155/2014/461724
- 41.Costi J, Stokes I, Gardner-Morse M, Iatridis JC (2008) Frequency-dependent behavior of the intervertebral disc in response to each of six degree of freedom dynamic loading: solid phase and fluid phase contributions. Spine (Phila Pa 1976) 33:173–1738. https://doi.org/10.3816/CLM.2009.n.003.Novel. CrossRefGoogle Scholar
- 43.Galbusera F, Schmidt H, Neidlinger-Wilke C, Wilke H-J (2011) The effect of degenerative morphological changes of the intervertebral disc on the lumbar spine biomechanics: a poroelastic finite element investigation. Comput Methods Biomech Biomed Eng 14:729–739. https://doi.org/10.1080/10255842.2010.493522 CrossRefGoogle Scholar
- 44.Galbusera F, Schmidt H, Neidlinger-Wilke C, Gottschalk A, Wilke HJ (2011) The mechanical response of the lumbar spine to different combinations of disc degenerative changes investigated using randomized poroelastic finite element models. Eur Spine J 20:563–571. https://doi.org/10.1007/s00586-010-1586-4 CrossRefPubMedGoogle Scholar
- 46.Malandrino A, Pozo JM, Castro-Mateos I, Frangi AF, van Rijsbergen MM, Ito K et al (2015) On the relative relevance of subject-specific geometries and degeneration-specific mechanical properties for the study of cell death in human intervertebral disk models. Front Bioeng Biotechnol 3:5. https://doi.org/10.3389/fbioe.2015.00005 CrossRefPubMedPubMedCentralGoogle Scholar
- 47.van Rijsbergen MM, Barthelemy VMP, Vrancken ACT, Crijns SPM, Wilke HJ, Wilson W et al (2016) Moderately degenerated lumbar motion segments: are they truly unstable? Biomech Model Mechanobiol:1–11. https://doi.org/10.1007/s10237-016-0835-9
- 50.Cegoñino J, Moramarco V, Calvo-Echenique A, Pappalettere C, Pérez Del Palomar A (2014) A constitutive model for the annulus of human intervertebral disc (IVD): implications for developing a degeneration model and its influence on lumbar spine functioning. J Appl Math 2014. https://doi.org/10.1155/2014/658719