Intervertebral disc (IVD) degeneration (IVDD) leads to structural and functional changes. Biomaterials for restoring IVD function and promoting regeneration are currently being investigated; however, such approaches require validation using animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Herein, we comprehensively characterized a sheep model of chondroitinase-ABC (C-ABC) induced IVDD. Briefly, C-ABC (1U) was injected into the L1/2, L2/3, and L3/4 IVDs. Degeneration was assessed via longitudinal magnetic resonance (MR) and radiographic imaging. Additionally, kinematic, biochemical, and histological analyses were performed on explanted functional spinal units (FSUs). At 17-weeks, C-ABC treated IVDs demonstrated significant reductions in MR index (p=0.030) and disc height (p=0.009) compared to pre-operative values. Additionally, C-ABC treated IVDs exhibited significantly increased creep displacement (p=0.004) and axial range of motion (p=0.007) concomitant with significant decreases in tensile (p=0.034) and torsional (p=0.021) stiffnesses and long-term viscoelastic properties (p=0.016). C-ABC treated IVDs also exhibited a significant decrease in NP glycosaminoglycan : hydroxyproline ratio (p=0.002) and changes in microarchitecture, particularly in the NP and endplates, compared to uninjured IVDs. Taken together, this study demonstrated that intradiscal injection of C-ABC induces significant degeneration in sheep lumbar IVDs and its potential for use in evaluating biomaterials for IVD repair.

中文翻译：

---

旨在评估生物材料的绵羊模型中软骨素酶诱导的腰椎间盘退变的特征

椎间盘（IVD）变性（IVDD）导致结构和功能改变。目前正在研究恢复体外诊断功能并促进再生的生物材料。但是，这种方法需要使用动物模型进行验证，该模型可以概括人类病理学的临床，生化和生物力学特征。在这里，我们全面表征了软骨素酶-ABC（C-ABC）诱导的IVDD的绵羊模型。简而言之，将C-ABC（1U）注入到L1 / 2，L2 / 3和L3 / 4 IVD中。通过纵向磁共振（MR）和射线照相成像评估变性。此外，对移植的功能性脊柱单位（FSU）进行了运动学，生化和组织学分析。在17周时，经C-ABC处理的IVD表现出MR指数（p = 0.030）和椎间盘高度（p = 0）明显降低。009）与术前值比较。此外，经C-ABC处理的IVD表现出蠕变位移（p = 0.004）和轴向运动范围（p = 0.007）显着增加，同时抗拉刚度（p = 0.034）和扭转刚度（p = 0.021）和长期刚度显着降低粘弹性（p ＝ 0.016）。与未受伤的IVD相比，经C-ABC处理的IVD还显示出NP糖胺聚糖：羟脯氨酸的比率显着降低（p = 0.002），并且微结构的变化，特别是NP和终板。综上所述，这项研究表明，椎间盘内注射C-ABC会导致绵羊腰部IVD发生明显的变性，并具有用于评估IVD修复生物材料的潜力。004）和轴向运动范围（p = 0.007），同时抗拉刚度（p = 0.034）和扭转刚度（p = 0.021）和长期粘弹性（p = 0.016）显着降低。与未受伤的IVD相比，经C-ABC处理的IVD还显示出NP糖胺聚糖：羟脯氨酸的比率显着降低（p = 0.002），并且微结构的变化，特别是NP和终板。综上所述，这项研究表明，椎间盘内注射C-ABC会导致绵羊腰部IVD发生明显的变性，并具有用于评估IVD修复生物材料的潜力。004）和轴向运动范围（p = 0.007），同时抗拉刚度（p = 0.034）和扭转刚度（p = 0.021）和长期粘弹性（p = 0.016）显着降低。与未受伤的IVD相比，经C-ABC处理的IVD还显示出NP糖胺聚糖：羟脯氨酸的比率显着降低（p = 0.002），并且微结构的变化，特别是NP和终板。综上所述，这项研究表明，椎间盘内注射C-ABC会导致绵羊腰部IVD发生明显的变性，并具有用于评估IVD修复生物材料的潜力。与未损伤的IVD相比，羟脯氨酸比率（p = 0.002）和微结构的变化，尤其是NP和终板的变化。综上所述，这项研究表明，椎间盘内注射C-ABC会导致绵羊腰部IVD发生明显的变性，并具有用于评估IVD修复生物材料的潜力。与未损伤的IVD相比，羟脯氨酸比率（p = 0.002）和微结构的变化，尤其是NP和终板的变化。综上所述，这项研究表明，椎间盘内注射C-ABC会导致绵羊腰部IVD发生明显的变性，并具有用于评估IVD修复生物材料的潜力。