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Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model

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 injur...

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Autores principales: Long, Rose G., Ferguson, Stephen J., Benneker, Lorin M., Sakai, Daisuke, Li, Zhen, Pandit, Abhay, Grijpma, Dirk W., Eglin, David, Zeiter, Stephan, Schmid, Tanja, Eberli, Ursula, Nehrbass, Dirk, Di Pauli von Treuheim, Theodor, Alini, Mauro, Iatridis, James C., Grad, Sibylle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084058/
https://www.ncbi.nlm.nih.gov/pubmed/32211587
http://dx.doi.org/10.1002/jsp2.1074
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author Long, Rose G.
Ferguson, Stephen J.
Benneker, Lorin M.
Sakai, Daisuke
Li, Zhen
Pandit, Abhay
Grijpma, Dirk W.
Eglin, David
Zeiter, Stephan
Schmid, Tanja
Eberli, Ursula
Nehrbass, Dirk
Di Pauli von Treuheim, Theodor
Alini, Mauro
Iatridis, James C.
Grad, Sibylle
author_facet Long, Rose G.
Ferguson, Stephen J.
Benneker, Lorin M.
Sakai, Daisuke
Li, Zhen
Pandit, Abhay
Grijpma, Dirk W.
Eglin, David
Zeiter, Stephan
Schmid, Tanja
Eberli, Ursula
Nehrbass, Dirk
Di Pauli von Treuheim, Theodor
Alini, Mauro
Iatridis, James C.
Grad, Sibylle
author_sort Long, Rose G.
collection PubMed
description 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.
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spelling pubmed-70840582020-03-24 Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model Long, Rose G. Ferguson, Stephen J. Benneker, Lorin M. Sakai, Daisuke Li, Zhen Pandit, Abhay Grijpma, Dirk W. Eglin, David Zeiter, Stephan Schmid, Tanja Eberli, Ursula Nehrbass, Dirk Di Pauli von Treuheim, Theodor Alini, Mauro Iatridis, James C. Grad, Sibylle JOR Spine Research Articles 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. John Wiley & Sons, Inc. 2019-12-21 /pmc/articles/PMC7084058/ /pubmed/32211587 http://dx.doi.org/10.1002/jsp2.1074 Text en © 2019 The Authors. JOR Spine published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Long, Rose G.
Ferguson, Stephen J.
Benneker, Lorin M.
Sakai, Daisuke
Li, Zhen
Pandit, Abhay
Grijpma, Dirk W.
Eglin, David
Zeiter, Stephan
Schmid, Tanja
Eberli, Ursula
Nehrbass, Dirk
Di Pauli von Treuheim, Theodor
Alini, Mauro
Iatridis, James C.
Grad, Sibylle
Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model
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 Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084058/
https://www.ncbi.nlm.nih.gov/pubmed/32211587
http://dx.doi.org/10.1002/jsp2.1074
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