Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model
Abstract Tissue engineering repair of annulus fibrosus (AF) defects has the potential to prevent disability and pain from intervertebral disc (IVD) herniation and its progression to degeneration. Clinical translation of AF repair methods requires assessment in long‐term large animal models. An ovine...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-03-01
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| Series: | JOR Spine |
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| Online Access: | https://doi.org/10.1002/jsp2.1074 |
| _version_ | 1811336080153116672 |
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| author | Rose G. Long Stephen J. Ferguson Lorin M. Benneker Daisuke Sakai Zhen Li Abhay Pandit Dirk W. Grijpma David Eglin Stephan Zeiter Tanja Schmid Ursula Eberli Dirk Nehrbass Theodor Di Pauli von Treuheim Mauro Alini James C. Iatridis Sibylle Grad |
| author_facet | Rose G. Long Stephen J. Ferguson Lorin M. Benneker Daisuke Sakai Zhen Li Abhay Pandit Dirk W. Grijpma David Eglin Stephan Zeiter Tanja Schmid Ursula Eberli Dirk Nehrbass Theodor Di Pauli von Treuheim Mauro Alini James C. Iatridis Sibylle Grad |
| author_sort | Rose G. Long |
| collection | DOAJ |
| description | Abstract Tissue engineering repair of annulus fibrosus (AF) defects has the potential to prevent disability and pain from intervertebral disc (IVD) herniation and its progression to degeneration. Clinical translation of AF repair methods requires assessment in long‐term large animal models. An ovine AF injury model was developed using cervical spinal levels and a biopsy‐type AF defect to assess composite tissue engineering repair in 1‐month and 12‐month studies. The repair used a fibrin hydrogel crosslinked with genipin (FibGen) to seal defects, poly(trimethylene carbonate) (PTMC) scaffolds to replace lost AF tissue, and polyurethane membranes to prevent herniation. In the 1‐month study, PTMC scaffolds sealed with FibGen herniated with polyurethane membranes. When applied alone, FibGen integrated with the surrounding AF tissue without herniation, showing promise for long‐term studies. The 12‐month long‐term study used only FibGen which showed fibrous healing, biomaterial resorption and no obvious hydrogel‐related complications. However, the 2 mm biopsy punch injury condition also exhibited fibrotic healing at 12 months. Both untreated and FibGen treated groups showed equivalency with no detectable differences in histological grades of proteoglycans, cellular morphology, IVD structure and blood vessel formation, biomechanical properties including torque range and axial range of motion, Pfirrmann grade, IVD height, and quantitative scores of vertebral body changes from clinical computed tomography. The biopsy‐type injury caused endplate defects with a high prevalence of osteophytes in all groups and no nucleus herniation, indicating that the biopsy‐type injury requires further refinement, such as reduction to a slit‐type defect that could penetrate the full depth of the AF without damaging the endplate. Results demonstrate translational feasibility of FibGen for AF repair to seal AF defects, although future study with a more refined injury model is required to validate the efficacy of FibGen before translation. |
| first_indexed | 2024-04-13T17:34:17Z |
| format | Article |
| id | doaj.art-6bb77191b8bd4216982cfa6341fd9e2d |
| institution | Directory Open Access Journal |
| issn | 2572-1143 |
| language | English |
| last_indexed | 2024-04-13T17:34:17Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | JOR Spine |
| spelling | doaj.art-6bb77191b8bd4216982cfa6341fd9e2d2022-12-22T02:37:28ZengWileyJOR Spine2572-11432020-03-0131n/an/a10.1002/jsp2.1074Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical modelRose G. Long0Stephen J. Ferguson1Lorin M. Benneker2Daisuke Sakai3Zhen Li4Abhay Pandit5Dirk W. Grijpma6David Eglin7Stephan Zeiter8Tanja Schmid9Ursula Eberli10Dirk Nehrbass11Theodor Di Pauli von Treuheim12Mauro Alini13James C. Iatridis14Sibylle Grad15Department of Genetics Harvard Medical School Boston MassachusettsETH Zurich, Institute for Biomechanics Zurich SwitzerlandDepartment for Orthopaedic Surgery, Spine Unit, Inselspital University Hospital of Bern Bern SwitzerlandDepartment of Orthopaedic Surgery Tokai University School of Medicine Kanagawa JapanAO Research Institute Davos Davos Platz SwitzerlandCÚRAM, Center for Research in Medical Devices National University of Ireland Galway IrelandUniversity of Twente, Technical Medical Centre Department of Biomaterials Science and Technology Faculty of Science and Technology Enschede The NetherlandsAO Research Institute Davos Davos Platz SwitzerlandAO Research Institute Davos Davos Platz SwitzerlandAO Research Institute Davos Davos Platz SwitzerlandAO Research Institute Davos Davos Platz SwitzerlandAO Research Institute Davos Davos Platz SwitzerlandLeni & Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New YorkAO Research Institute Davos Davos Platz SwitzerlandLeni & Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New YorkAO Research Institute Davos Davos Platz SwitzerlandAbstract Tissue engineering repair of annulus fibrosus (AF) defects has the potential to prevent disability and pain from intervertebral disc (IVD) herniation and its progression to degeneration. Clinical translation of AF repair methods requires assessment in long‐term large animal models. An ovine AF injury model was developed using cervical spinal levels and a biopsy‐type AF defect to assess composite tissue engineering repair in 1‐month and 12‐month studies. The repair used a fibrin hydrogel crosslinked with genipin (FibGen) to seal defects, poly(trimethylene carbonate) (PTMC) scaffolds to replace lost AF tissue, and polyurethane membranes to prevent herniation. In the 1‐month study, PTMC scaffolds sealed with FibGen herniated with polyurethane membranes. When applied alone, FibGen integrated with the surrounding AF tissue without herniation, showing promise for long‐term studies. The 12‐month long‐term study used only FibGen which showed fibrous healing, biomaterial resorption and no obvious hydrogel‐related complications. However, the 2 mm biopsy punch injury condition also exhibited fibrotic healing at 12 months. Both untreated and FibGen treated groups showed equivalency with no detectable differences in histological grades of proteoglycans, cellular morphology, IVD structure and blood vessel formation, biomechanical properties including torque range and axial range of motion, Pfirrmann grade, IVD height, and quantitative scores of vertebral body changes from clinical computed tomography. The biopsy‐type injury caused endplate defects with a high prevalence of osteophytes in all groups and no nucleus herniation, indicating that the biopsy‐type injury requires further refinement, such as reduction to a slit‐type defect that could penetrate the full depth of the AF without damaging the endplate. Results demonstrate translational feasibility of FibGen for AF repair to seal AF defects, although future study with a more refined injury model is required to validate the efficacy of FibGen before translation.https://doi.org/10.1002/jsp2.1074annulus fibrosusintervertebral discintervertebral disc herniationovine in vivo modeltissue engineering |
| spellingShingle | Rose G. Long Stephen J. Ferguson Lorin M. Benneker Daisuke Sakai Zhen Li Abhay Pandit Dirk W. Grijpma David Eglin Stephan Zeiter Tanja Schmid Ursula Eberli Dirk Nehrbass Theodor Di Pauli von Treuheim Mauro Alini James C. Iatridis Sibylle Grad Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model JOR Spine annulus fibrosus intervertebral disc intervertebral disc herniation ovine in vivo model tissue engineering |
| title | Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model |
| title_full | Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model |
| title_fullStr | Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model |
| title_full_unstemmed | Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model |
| title_short | Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model |
| title_sort | morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model |
| topic | annulus fibrosus intervertebral disc intervertebral disc herniation ovine in vivo model tissue engineering |
| url | https://doi.org/10.1002/jsp2.1074 |
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