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Persistent degenerative changes in the intervertebral disc after burst fracture in an in vitro model mimicking physiological post-traumatic conditions

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Abstract

Purpose

Post-traumatic disc degeneration (DD) is currently investigated with models not fully matching the clinical condition, in particular post-traumatic loading of the disc is not considered. Therefore, the aim was to establish an in vitro burst fracture model that more closely mimics the in vivo situation by including post-traumatic physiological loading and to investigate DD under these conditions.

Methods

72 rabbit spinal segments (disc/endplates + 1/3 of adjacent vertebrae) were harvested from T8/9 to L5/6 and assigned to control (n = 36) or trauma groups (n = 36). Burst fractures were induced at day 0 in the trauma group using a dropped-weight device. From day 1 to 28, all specimens were cultured at 37 °C and were dynamically loaded daily (~1 MPa nominal pressure, 1 Hz, 2,500 cycles). At day 1, 7, 14, and 28, 9 specimens from each group were taken for analysis: histology (n = 2), total disc glycosaminoglycan (GAG) content (n = 3) normalized to DNA, and qPCR of DD marker genes (n = 4) in the nucleus pulposus and the annulus fibrosus.

Results

Burst fracture with post-traumatic physiological loading resulted in a 65 % loss of GAG/DNA by day 28. Histological sections confirmed the remodeling of the matrix. Catabolic (MMP-1/-3), pro-apoptotic (TNF-α, fas ligand), and pro-inflammatory (IL-1/-6, iNOS) gene transcription was substantially up-regulated in the nucleus after the trauma and did not normalize to control within 28 days. Similar results were found for the annulus on lower levels.

Conclusion

An in vitro burst fracture model with physiological post-traumatic loading was established. Under these conditions, burst spinal segments undergo strong and persistent degenerative changes.

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Acknowledgments

We thank Jochen Walser and Peter Schwilch for their help with the design of the loading device. This study was funded by the Swiss National Science Foundation #310000-122105.

Conflict of interest

None of the authors has any potential conflict of interest.

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Correspondence to Stefan Dudli.

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Dudli, S., Haschtmann, D. & Ferguson, S.J. Persistent degenerative changes in the intervertebral disc after burst fracture in an in vitro model mimicking physiological post-traumatic conditions. Eur Spine J 24, 1901–1908 (2015). https://doi.org/10.1007/s00586-014-3301-3

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  • DOI: https://doi.org/10.1007/s00586-014-3301-3

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