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 (ChABC) induced IVDD. Briefly, ChABC (1 U) was injected into the L_1/2, L_2/3, and L_3/4 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, ChABC treated IVDs demonstrated significant reductions in MR index (p = 0.030) and disc height (p = 0.009) compared with pre‐operative values. Additionally, ChABC 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). ChABC 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 with uninjured IVDs. Taken together, this study demonstrated that intradiscal injection of ChABC induces significant degeneration in sheep lumbar IVDs and the potential for using this model in evaluating biomaterials for IVD repair, regeneration, or fusion.

中文翻译：

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在用于评估生物材料的绵羊模型中表征软骨素酶诱导的腰椎间盘退变

椎间盘 (IVD) 退化 (IVDD) 导致结构和功能变化。目前正在研究恢复体外诊断功能和促进再生的生物材料；然而，这些方法需要使用能够概括人类病理学的临床、生化和生物力学特征的动物模型进行验证。在此，我们全面表征了软骨素酶-ABC (ChABC) 诱导的 IVDD 绵羊模型。简而言之，将 ChABC (1 U) 注入 L _1/2、L _2/3和 L _3/4体外诊断设备。通过纵向磁共振 (MR) 和放射成像评估退化。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，与术前值相比，ChABC 治疗的 IVD 显示 MR 指数 ( p = 0.030) 和椎间盘高度 ( p = 0.009) 显着降低。此外，ChABC 处理的体外诊断器械表现出显着增加的蠕变位移 ( p = 0.004) 和轴向运动范围 ( p = 0.007)，同时拉伸 ( p = 0.034) 和扭转 ( p = 0.021) 刚度和长期粘弹性性能显着降低( p= 0.016)。与未受伤的 IVD 相比，ChABC 处理的 IVD 还表现出 NP 糖胺聚糖：羟脯氨酸比率 ( p = 0.002) 和微结构的显着降低，特别是在 NP 和终板中。总之，这项研究表明，ChABC 的椎间盘内注射会导致羊腰椎 IVD 显着退化，以及使用该模型评估用于 IVD 修复、再生或融合的生物材料的潜力。