The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA.
Department of Radiology, Greenville Health System, Greenville, South Carolina, USA.
J Biomed Mater Res A. 2021 Jul;109(7):1232-1246. doi: 10.1002/jbm.a.37117. Epub 2020 Oct 22.
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 , L , and L 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.
椎间盘（IVD）退变（IVDD）导致结构和功能改变。目前正在研究用于恢复 IVD 功能和促进再生的生物材料；然而，此类方法需要使用能够重现人类病理学的临床、生化和生物力学特征的动物模型进行验证。在此，我们全面描述了软骨素酶 ABC（ChABC）诱导的 IVDD 绵羊模型。简要地，将 ChABC（1U）注入 L 、 L 和 L IVD。通过纵向磁共振（MR）和放射影像学评估退变。此外，对离体功能脊柱单元（FSU）进行运动学、生化和组织学分析。在 17 周时，与术前值相比，ChABC 处理的 IVD 的 MR 指数（p=0.030）和椎间盘高度（p=0.009）显著降低。此外，ChABC 处理的 IVD 表现出明显增加的蠕变位移（p=0.004）和轴向运动范围（p=0.007），同时伴随着拉伸（p=0.034）和扭转（p=0.021）刚度以及长期粘弹性性质（p=0.016）的显著降低。与未受伤的 IVD 相比，ChABC 处理的 IVD 的 NP 糖胺聚糖：羟脯氨酸比（p=0.002）和微结构变化，特别是 NP 和终板也明显降低。总之，这项研究表明，椎间盘内注射 ChABC 可在绵羊腰椎 IVD 中引起明显退变，并有可能在评估用于 IVD 修复、再生或融合的生物材料时使用该模型。
