Comparison and optimization of sheep in vivo intervertebral disc injury model.
annulus fibrosus defect
discectomy
intervertebral disc degeneration
intervertebral disc injury
preclinical model
sheep
Journal
JOR spine
ISSN: 2572-1143
Titre abrégé: JOR Spine
Pays: United States
ID NLM: 101722350
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
14
09
2021
revised:
08
03
2022
accepted:
16
03
2022
entrez:
5
7
2022
pubmed:
6
7
2022
medline:
6
7
2022
Statut:
epublish
Résumé
The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box-cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre- and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading). All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box-cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box-cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height. The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.
Sections du résumé
Background
UNASSIGNED
The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare
Methods
UNASSIGNED
Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box-cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre- and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading).
Results
UNASSIGNED
All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box-cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box-cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height.
Conclusions
UNASSIGNED
The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.
Identifiants
pubmed: 35783908
doi: 10.1002/jsp2.1198
pii: JSP21198
pmc: PMC9238284
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e1198Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR057397
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR080096
Pays : United States
Informations de copyright
© 2022 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest
Références
Spine J. 2011 Oct;11(10):947-60
pubmed: 21843975
Spine (Phila Pa 1976). 2011 Dec 1;36(25):2147-51
pubmed: 21343849
Spine (Phila Pa 1976). 2001 Mar 1;26(5):E93-E113
pubmed: 11242399
J Occup Rehabil. 2009 Dec;19(4):419-26
pubmed: 19760488
J Neurosurg Spine. 2014 Jun;20(6):657-69
pubmed: 24702507
Eur Spine J. 2008 Sep;17(9):1131-48
pubmed: 18584218
Spine (Phila Pa 1976). 2017 Jul 15;42(14):1106-1114
pubmed: 28146015
Acta Biomater. 2015 Oct;26:215-24
pubmed: 26116448
Eur Spine J. 2014 Jan;23(1):19-26
pubmed: 24121748
Spine (Phila Pa 1976). 2014 Mar 15;39(6):E369-78
pubmed: 24384655
Biomed Res Int. 2016;2016:5952165
pubmed: 27314030
J Neurosurg Spine. 2010 Jun;12(6):680-6
pubmed: 20515355
J Bone Joint Surg Am. 2003 Jan;85(1):102-8
pubmed: 12533579
Spine (Phila Pa 1976). 1991 Jun;16(6):641-6
pubmed: 1862403
Spine (Phila Pa 1976). 2007 Nov 15;32(24):E708-12
pubmed: 18007231
Spine (Phila Pa 1976). 2012 Jan 1;37(1):18-25
pubmed: 22179320
Spine (Phila Pa 1976). 2009 Jun 15;34(14):1457-63
pubmed: 19525836
Spine (Phila Pa 1976). 2018 Feb 15;43(4):E208-E215
pubmed: 28719551
Clinicoecon Outcomes Res. 2018 Jun 26;10:349-357
pubmed: 29983583
Spine (Phila Pa 1976). 2008 Mar 15;33(6):588-96
pubmed: 18344851
J Bone Joint Surg Am. 1995 Jan;77(1):26-31
pubmed: 7822352
J Neurosurg Spine. 2016 May;24(5):715-26
pubmed: 26799116
Global Spine J. 2013 Jun;3(3):145-52
pubmed: 24436865
Eur Spine J. 1997;6(6):376-84
pubmed: 9455664
Spine (Phila Pa 1976). 1994 Apr 15;19(8):948-54
pubmed: 8009354
Neurosurg Clin N Am. 1991 Oct;2(4):791-806
pubmed: 1821758
Spine (Phila Pa 1976). 2010 Aug 15;35(18):1714-20
pubmed: 21374895
Spine (Phila Pa 1976). 2007 Feb 1;32(3):328-33
pubmed: 17268264
J Tissue Eng Regen Med. 2015 Apr;9(4):405-14
pubmed: 24227682
Spine (Phila Pa 1976). 2003 Dec 1;28(23):2570-6
pubmed: 14652473
AJR Am J Roentgenol. 2004 Aug;183(2):343-51
pubmed: 15269023
Spine (Phila Pa 1976). 1999 May 15;24(10):996-1002
pubmed: 10332792
Lab Anim Res. 2013 Dec;29(4):183-9
pubmed: 24396382
Spine (Phila Pa 1976). 2008 Dec 1;33(25):2789-800
pubmed: 19018250
J Neurosurg Spine. 2012 May;16(5):479-88
pubmed: 22404141
Spine (Phila Pa 1976). 2004 Dec 1;29(23):2742-50
pubmed: 15564923
Spine (Phila Pa 1976). 2001 Sep 1;26(17):1873-8
pubmed: 11568697
Anat Rec. 1997 Apr;247(4):542-55
pubmed: 9096794
Spine (Phila Pa 1976). 2002 Aug 15;27(16):1756-64
pubmed: 12195068
J Bone Joint Surg Am. 1990 Mar;72(3):403-8
pubmed: 2312537
Spine (Phila Pa 1976). 1997 Oct 15;22(20):2365-74
pubmed: 9355217
J Bone Joint Surg Am. 2011 Oct 19;93(20):1906-14
pubmed: 22012528
J Orthop Res. 1992 Sep;10(5):665-76
pubmed: 1500980
Int J Mol Sci. 2017 May 12;18(5):
pubmed: 28498326
Lancet. 1997 Jul 19;350(9072):178-81
pubmed: 9250186
Spine J. 2018 Mar;18(3):491-506
pubmed: 29055739
Ann N Y Acad Sci. 2019 Apr;1442(1):61-78
pubmed: 30604562
Spine (Phila Pa 1976). 1990 Aug;15(8):762-7
pubmed: 2237626
Spine (Phila Pa 1976). 2009 Sep 1;34(19):2044-51
pubmed: 19730212
JOR Spine. 2018 Oct 10;1(4):e1037
pubmed: 31463452
Eur Spine J. 2008 Jan;17(1):2-19
pubmed: 17632738
Spine (Phila Pa 1976). 2009 Jan 1;34(1):10-6
pubmed: 19127156
Spine (Phila Pa 1976). 2000 Sep 1;25(17):2165-70
pubmed: 10973397
J Tissue Eng Regen Med. 2018 Jan;12(1):e216-e226
pubmed: 27689852
Spine J. 2005 Nov-Dec;5(6 Suppl):267S-279S
pubmed: 16291123
Int J Biol Sci. 2009 Jun 03;5(5):388-96
pubmed: 19521550
J Tissue Eng Regen Med. 2018 Nov;12(11):2188-2202
pubmed: 30095863
Biometrics. 1977 Mar;33(1):159-74
pubmed: 843571
Spine (Phila Pa 1976). 2006 Mar 15;31(6):653-7
pubmed: 16540869
EBioMedicine. 2018 Nov;37:521-534
pubmed: 30389504
Neurosurgery. 2019 Aug 1;85(2):E350-E359
pubmed: 30476218
Sci Transl Med. 2020 Mar 11;12(534):
pubmed: 32161108
Spine J. 2012 Feb;12(2):89-97
pubmed: 22193055
Spine (Phila Pa 1976). 2014 Feb 1;39(3):198-206
pubmed: 24253790