College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom.
College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom.
J Biomech. 2022 Sep;142:111260. doi: 10.1016/j.jbiomech.2022.111260. Epub 2022 Aug 17.
The intervertebral disc (IVD) provides flexibility, acts as a shock absorber, and transmits load. Degeneration of the IVD includes alterations in the biomechanics, extracellular matrix (ECM), and cellular activity. These changes are not always perceived, however, IVD degeneration can lead to severe health problems including long-term disability. To understand the pathogenesis of IVD degeneration and suitable testing methods for emerging treatments and therapies, this review documents in-vitro models of IVD degeneration including physical disruption, hyperphysiological loading, ECM degradation by enzyme digestion, or a combination of these methods. This paper reviews and critically analyses the models of degeneration published since the year 2000 in either in human or animal specimens. The results are categorised in terms of the IVD biomechanics, physical attributes, ECM composition, tissue damage and cellularity to evaluate the models with respect to natural human degeneration, and to provide recommendations for clinically relevant models for the various stages of degeneration. There is no one model that replicates the wide range of degenerative changes that occur as part of normal degeneration. However, cyclic overloading replicates many aspects of degeneration, with the advantage of a dose-response allowing the tuning of damage initiated. Models of severe degeneration are currently lacking, but there is potential that combining cyclic overloading and enzymatic digestion will provide model that closely resembles human IVD degeneration. This will provide an effective way to investigate the effects of severe degeneration, and the evaluation of treatments for the IVD, which would generally be indicated at this advanced stage of degeneration.
椎间盘（IVD）提供灵活性，充当减震器，并传递负载。IVD 的退化包括生物力学、细胞外基质（ECM）和细胞活性的改变。然而，这些变化并不总是被察觉，IVD 退化可能导致严重的健康问题，包括长期残疾。为了了解 IVD 退化的发病机制和新兴治疗方法和疗法的合适测试方法，本综述记录了 IVD 退化的体外模型，包括物理破坏、超生理负荷、酶消化 ECM 降解或这些方法的组合。本文综述和批判性分析了自 2000 年以来在人体或动物标本中发表的退化模型。结果根据 IVD 生物力学、物理特性、ECM 组成、组织损伤和细胞活力进行分类，以评估模型与自然人类退化的相关性，并为各种退化阶段的临床相关模型提供建议。没有一种模型可以复制正常退化过程中发生的广泛退化变化。然而，循环超负荷复制了许多退化方面，具有剂量反应的优势，可以启动损伤的调整。目前严重退化的模型仍然缺乏，但有可能将循环超负荷和酶消化结合起来，提供一种更接近人类 IVD 退化的模型。这将为严重退化的影响以及 IVD 的治疗评估提供一种有效的方法，而在这种退化的晚期阶段，通常需要进行这些治疗。
