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Development of an ex vivo cavity model to study repair strategies in loaded intervertebral discs

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Abstract

Purpose

The aim of this study was to compare two approaches for the delivery of biomaterials to partially nucleotomised intervertebral discs in whole organ culture under loading. Such models can help to bridge the gap between in vitro and in vivo studies by assessing (1) suitability of biomaterial delivery and defect closure methods, (2) effect of mechanical loading and (3) tissue response.

Methods

Mechanical performance of bovine discs filled with a hyaluronan-based thermoreversible hydrogel delivered through the annulus fibrosus (AF) or the bony endplate (EP) was evaluated under cyclic axial loading in a bioreactor. The loading protocol was optimised to achieve physiological disc height changes in nucleotomised discs. A loading regime of 0.06 ± 0.02 MPa, 0.1 Hz, 6 h daily was applied on the nucleotomised discs. Disc height and stiffness were tracked for 5 days, followed by histological analyses.

Results

Creation of a defect is less demanding for AF approach, while sealing is superior with the EP approach. Dynamic compressive stiffness is reduced following nucleotomy, with no significant difference between the two approaches. Disc height loss was higher, disc height recovery was lower and region around the defect with reduced cell viability was smaller for AF-approached than EP-approached discs.

Conclusions

Two alternative methods for biomaterial testing in whole organ culture under loading were developed. Such models bring insights on the ability of the biomaterial to restore the mechanical behaviour of the discs. From a clinical perspective, the cavity models can simulate treatment of nucleotomy after disc herniation in young patients, whereby the remaining nucleus pulposus is still functional and therefore at high risk of re-herniation, though the defect may differ from the clinical situation.

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Acknowledgments

This study was supported by the European Commission under the FP7-NMP project NPmimetic (246351), AO Spine and North American Spine Society research grant. The authors gratefully acknowledge Stephan Zeiter for advice on suture techniques and Lorin Benneker for endplate approach development, Matteo D’Este and David Eglin for providing the hyaluronan hydrogel, Nora Goudsouzian and Mauro Bluvol for histological processing and Stephen Ferguson for valuable discussions.

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Authors and Affiliations

  1. AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland

    Zhen Li, Patrick Lezuo, Girish Pattappa, Mauro Alini, Sibylle Grad & Marianna Peroglio

  2. Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland

    Estelle Collin

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  1. Zhen Li
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Correspondence to Marianna Peroglio.

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Li, Z., Lezuo, P., Pattappa, G. et al. Development of an ex vivo cavity model to study repair strategies in loaded intervertebral discs. Eur Spine J 25, 2898–2908 (2016). https://doi.org/10.1007/s00586-016-4542-0

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  • DOI: https://doi.org/10.1007/s00586-016-4542-0

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