Constant Caroline, Hom Warren W, Nehrbass Dirk, Carmel Eric-Norman, Albers Christoph E, Deml Moritz C, Gehweiler Dominic, Lee Yunsoo, Hecht Andrew, Grad Sibylle, Iatridis James C, Zeiter Stephan
AO Research Institute Davos Davos Switzerland.
Department of Orthopaedics Icahn School of Medicine, Mount Sinai Health System New York New York USA.
JOR Spine. 2022 Apr 22;5(2):e1198. doi: 10.1002/jsp2.1198. eCollection 2022 Jun.
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 IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies.
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.
目前椎间盘（IVD）突出症的标准治疗方法是手术椎间盘切除术，但该方法无法修复纤维环（AF）缺损，部分原因是缺乏有效的修复方法，这也是新的修复策略在临床前得到广泛研究和测试的原因。需要在大型动物中建立标准化的IVD损伤模型，以便对临床前研究结果进行比较和解读。本研究的目的是比较绵羊的IVD损伤模型，以确定哪种纤维环（AF）缺损类型与部分髓核（NP）切除相结合能更好地模拟人类脊柱退行性病变。
将6只骨骼成熟的绵羊随机分配到两个观察期（1个月和3个月）之一，采用外侧腹膜后手术入路，在三个腰椎水平创建3种不同的AF缺损类型（裂隙、十字形和方形切除AF缺损），并切除0.1 g NP。术前、术后2周、安乐死时通过临床CT扫描监测脊柱，安乐死后通过磁共振成像（MRI）和组织学检查确定退变的严重程度（椎间盘高度丢失、Pfirrmann分级、半定量组织病理学分级）。
所有AF缺损在CT和MR图像上均导致明显的退行性改变，导致椎间盘组织膨出但无椎间盘突出，并导致退行性和炎症性组织病理学改变。然而术后3个月时，AF缺损在椎间盘高度丢失方面并不相同；十字形和方形切除AF缺损与术前高度相比椎间盘高度显著降低，方形切除缺损导致的椎间盘高度丢失最大，而裂隙AF缺损显示术前正常椎间盘高度得以恢复。
所测试的IVD损伤模型并非都能产生可比的椎间盘退变，但可被认为是研究新治疗方法的合适IVD损伤模型。本研究结果清楚表明，如果将椎间盘高度作为主要结果之一，应避免使用裂隙AF缺损；可能需要更多的验证性研究来推广这一发现
