Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors
Abstract Bioreactors have become indispensable tools in spine research, enabling long‐term intervertebral disc culture under controlled biological and mechanical conditions. Conventional systems are often limited to uniaxial loading, restricting their ability to replicate the complex, multidirection...
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Wiley
2025-07-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.70033 |
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| author | Amra Šećerović Aapo Ristaniemi Francesco Crivelli Sarah Heub Mauro Alini Gilles Weder Diane Ledroit Stephen J. Ferguson Sibylle Grad |
| author_facet | Amra Šećerović Aapo Ristaniemi Francesco Crivelli Sarah Heub Mauro Alini Gilles Weder Diane Ledroit Stephen J. Ferguson Sibylle Grad |
| author_sort | Amra Šećerović |
| collection | DOAJ |
| description | Abstract Bioreactors have become indispensable tools in spine research, enabling long‐term intervertebral disc culture under controlled biological and mechanical conditions. Conventional systems are often limited to uniaxial loading, restricting their ability to replicate the complex, multidirectional biomechanics of the spine. To overcome this limitation, we developed a next‐generation bioreactor capable of simulating multiaxial motions while preserving the disc's biological environment. In this study, we investigated the effects of complex loading patterns on early disc degeneration by subjecting bovine whole‐organ discs to combined extension, lateral bending, and torsion at 0.3 Hz for 2 h daily over 14 days. To assess the impact of loading magnitude and the specific contribution of torsion, discs were exposed to either low‐ or high‐angle rotations, with or without torsional loading at higher angles. Histological analysis revealed a marked loss of glycosaminoglycans (GAG) and collagen type II within the inner annulus fibrosus and transitional nucleus pulposus (NP), encompassing the transition zone (TZ), as well as GAG depletion in the central NP. Matrix degradation was observed across all loading conditions, with the most severe breakdown occurring under high‐angle extension, bending, and torsion. All loading regimes induced cell death in the TZ and central NP, although torsion‐free loading better maintained cell viability. These findings highlight the TZ, alongside the commonly affected NP, as a critical early site of degeneration. The study further underscores the importance of incorporating multiaxial loading in disc degeneration models and provides new insights into the biomechanical mechanisms underlying disc pathology. |
| format | Article |
| id | doaj-art-c28402a4f8ff4ba7b4151ef2d7d2cba3 |
| institution | DOAJ |
| issn | 2380-6761 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-c28402a4f8ff4ba7b4151ef2d7d2cba32025-08-20T03:14:08ZengWileyBioengineering & Translational Medicine2380-67612025-07-01104n/an/a10.1002/btm2.70033Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactorsAmra Šećerović0Aapo Ristaniemi1Francesco Crivelli2Sarah Heub3Mauro Alini4Gilles Weder5Diane Ledroit6Stephen J. Ferguson7Sibylle Grad8AO Research Institute Davos Davos SwitzerlandAO Research Institute Davos Davos SwitzerlandSwiss Center for Electronics and Microtechnology Alpnach SwitzerlandSwiss Center for Electronics and Microtechnology Neuchatel SwitzerlandAO Research Institute Davos Davos SwitzerlandSwiss Center for Electronics and Microtechnology Neuchatel SwitzerlandSwiss Center for Electronics and Microtechnology Neuchatel SwitzerlandETH Zürich Institute for Biomechanics Zürich SwitzerlandAO Research Institute Davos Davos SwitzerlandAbstract Bioreactors have become indispensable tools in spine research, enabling long‐term intervertebral disc culture under controlled biological and mechanical conditions. Conventional systems are often limited to uniaxial loading, restricting their ability to replicate the complex, multidirectional biomechanics of the spine. To overcome this limitation, we developed a next‐generation bioreactor capable of simulating multiaxial motions while preserving the disc's biological environment. In this study, we investigated the effects of complex loading patterns on early disc degeneration by subjecting bovine whole‐organ discs to combined extension, lateral bending, and torsion at 0.3 Hz for 2 h daily over 14 days. To assess the impact of loading magnitude and the specific contribution of torsion, discs were exposed to either low‐ or high‐angle rotations, with or without torsional loading at higher angles. Histological analysis revealed a marked loss of glycosaminoglycans (GAG) and collagen type II within the inner annulus fibrosus and transitional nucleus pulposus (NP), encompassing the transition zone (TZ), as well as GAG depletion in the central NP. Matrix degradation was observed across all loading conditions, with the most severe breakdown occurring under high‐angle extension, bending, and torsion. All loading regimes induced cell death in the TZ and central NP, although torsion‐free loading better maintained cell viability. These findings highlight the TZ, alongside the commonly affected NP, as a critical early site of degeneration. The study further underscores the importance of incorporating multiaxial loading in disc degeneration models and provides new insights into the biomechanical mechanisms underlying disc pathology.https://doi.org/10.1002/btm2.70033bioreactorsintervertebral discmultiaxial loadingtransition zonewhole organ culture |
| spellingShingle | Amra Šećerović Aapo Ristaniemi Francesco Crivelli Sarah Heub Mauro Alini Gilles Weder Diane Ledroit Stephen J. Ferguson Sibylle Grad Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors Bioengineering & Translational Medicine bioreactors intervertebral disc multiaxial loading transition zone whole organ culture |
| title | Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors |
| title_full | Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors |
| title_fullStr | Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors |
| title_full_unstemmed | Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors |
| title_short | Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next‐generation bioreactors |
| title_sort | multiaxial rotational loading compromises the transition zone of the intervertebral disc ex vivo study using next generation bioreactors |
| topic | bioreactors intervertebral disc multiaxial loading transition zone whole organ culture |
| url | https://doi.org/10.1002/btm2.70033 |
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