Department of Orthopedics, Balgrist University Hospital, Zurich, Switzerland.
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
PLoS One. 2018 Dec 6;13(12):e0208460. doi: 10.1371/journal.pone.0208460. eCollection 2018.
The surgical standard of care for lumbar discectomy leaves the annulus fibrosus (AF) defect unrepaired, despite considerable risk for a recurrent herniation. Identification of a viable defect repair strategy has until now been elusive. The scope of this ex vivo biomechanical study was to evaluate crosslinking hydrogels as potentially promising AF defect sealants, and provide a baseline for their use in combination with collagen scaffolds that restore disc volume. This study directly compared genipin crosslinked fibrin hydrogel (FibGen) as a promising preclinical candidate against a clinically available adhesive composed of glutaraldehyde and albumin (BioGlue). Forty-two bovine coccygeal functional spine units (FSU) were randomly allocated into four groups, namely untreated (control, n = 12), repaired with either one of the tested hydrogels (BioGlue, n = 12; FibGen, n = 12), or FibGen used in combination with a collagen hydrogel scaffold (FibGen+Scaffold, n = 6). All specimens underwent a moderate mechanical testing protocol in intact, injured and repaired states. After completion of the moderate testing protocol, the samples underwent a ramp-to-failure test. Lumbar discectomy destabilized the FSU as quantified by increased torsional range of motion (28.0° (19.1, 45.1) vs. 41.39° (27.3, 84.9), p<0.001), torsional neutral zone (3.1° (1.2, 7.7) vs. 4.8° (2.1, 12.1), Z = -3.49, p < 0.001), hysteresis(24.4 J (12.8, 76.0) vs. 27.6 J (16.4, 54.4), Z = -2.61, p = 0.009), with loss of both disc height (7.0 mm (5.0, 10.5) vs 6.1 mm (4.0, 9.3), Z = -5.16, p < 0.001) and torsional stiffness (0.76 Nmdeg-1 (0.38, 1.07) vs. 0.66 Nmdeg-1 (0.38, 0.97), Z = -3.98, p < 0.001). Most FibGen repaired AF endured the entire testing procedure whereas only a minority of BioGlue repaired AF and all FibGen+Scaffold repaired AF failed (6/10 vs. 3/12 vs. 0/6 respectively, p = 0.041). Both BioGlue and FibGen+Scaffold repaired AF partially restored disc height (0.47 mm (0.07, 2.41), p = 0.048 and 1.52 mm (0.41, 2.57), p = 0.021 respectively) compared to sham treatment (0.08 mm (-0.63, 0.88)) whereas FibGen-only repaired AF had no such effect (0.04 mm (-0.73, 1.13), U = 48.0, p = 1). The AF injury model demonstrated considerable change of FSU mechanics that could be partially restored by use of an AF sealant. While inclusion of a volumetric collagen scaffold led to repair failure, use of FibGen alone demonstrated clinically relevant promise for prevention of mechanical reherniation, outperforming an FDA approved sealant in this ex vivo test series.
手术治疗腰椎间盘切除术时，纤维环（AF）缺陷未修复，尽管存在复发疝的相当大风险。直到现在，人们一直在寻找一种可行的缺陷修复策略。本体外生物力学研究的范围是评估交联水凝胶作为有希望的 AF 缺陷密封剂，并为它们与恢复椎间盘体积的胶原支架结合使用提供基线。本研究直接比较了基因交联纤维蛋白水凝胶（FibGen）作为一种有前途的临床前候选物，与由戊二醛和白蛋白组成的临床可用粘合剂（BioGlue）进行比较。42 个牛尾骨功能脊柱单位（FSU）被随机分配到四个组，即未处理（对照，n = 12）、用一种测试水凝胶修复（BioGlue，n = 12；FibGen，n = 12）或 FibGen 与胶原水凝胶支架联合使用（FibGen+支架，n = 6）。所有标本均在完整、损伤和修复状态下进行中度机械测试方案。中度测试方案完成后，样品进行斜坡至失效测试。腰椎间盘切除术使 FSU 不稳定，表现为扭转运动范围增加（28.0°（19.1，45.1）与 41.39°（27.3，84.9），p<0.001），扭转中立区（3.1°（1.2，7.7）与 4.8°（2.1，12.1），Z = -3.49，p < 0.001），滞后（24.4 J（12.8，76.0）与 27.6 J（16.4，54.4），Z = -2.61，p = 0.009），同时失去椎间盘高度（7.0 mm（5.0，10.5）与 6.1 mm（4.0，9.3），Z = -5.16，p < 0.001）和扭转刚度（0.76 Nmdeg-1（0.38，1.07）与 0.66 Nmdeg-1（0.38，0.97），Z = -3.98，p < 0.001）。大多数 FibGen 修复的 AF 能够承受整个测试过程，而只有少数 BioGlue 修复的 AF 和所有 FibGen+支架修复的 AF 失败（6/10 与 3/12 与 0/6，分别，p = 0.041）。BioGlue 和 FibGen+支架修复的 AF 部分恢复了椎间盘高度（0.47 mm（0.07，2.41），p = 0.048 和 1.52 mm（0.41，2.57），p = 0.021）与 sham 治疗（0.08 mm（-0.63，0.88）相比，而 FibGen 单独修复的 AF 则没有这种效果（0.04 mm（-0.73，1.13），U = 48.0，p = 1）。AF 损伤模型显示 FSU 力学发生了相当大的变化，使用 AF 密封剂可以部分恢复。虽然包含体积胶原支架导致修复失败，但单独使用 FibGen 显示出预防机械复发的临床相关前景，在本体外测试系列中优于 FDA 批准的密封剂。
