Lazaro-Pacheco Daniela, Mohseni Mina, Rudd Samuel, Cooper-White Justin, Holsgrove Timothy Patrick
Department of Engineering, University of Exeter, Harrison Building, Streatham Campus, North Park Road, Exeter EX4 4QF, United Kingdom.
School of Chemical Engineering, The University of Queensland, St. Lucia QLD 4072, Australia.
APL Bioeng. 2023 May 8;7(2):021501. doi: 10.1063/5.0137698. eCollection 2023 Jun.
Low back pain is the leading cause of disability, producing a substantial socio-economic burden on healthcare systems worldwide. Intervertebral disc (IVD) degeneration is a primary cause of lower back pain, and while regenerative therapies aimed at full functional recovery of the disc have been developed in recent years, no commercially available, approved devices or therapies for the regeneration of the IVD currently exist. In the development of these new approaches, numerous models for mechanical stimulation and preclinical assessment, including cell studies using microfluidics, organ studies coupled with bioreactors and mechanical testing rigs, and testing in a variety of large and small animals, have emerged. These approaches have provided different capabilities, certainly improving the preclinical evaluation of these regenerative therapies, but challenges within the research environment, and compromises relating to non-representative mechanical stimulation and unrealistic test conditions, remain to be resolved. In this review, insights into the ideal characteristics of a disc model for the testing of IVD regenerative approaches are first assessed. Key learnings from , , and IVD models under mechanical loading stimulation to date are presented alongside the merits and limitations of each model based on the physiological resemblance to the human IVD environment (biological and mechanical) as well as the possible feedback and output measurements for each approach. When moving from simplified models to and approaches, the complexity increases resulting in less controllable models but providing a better representation of the physiological environment. Although cost, time, and ethical constraints are dependent on each approach, they escalate with the model complexity. These constraints are discussed and weighted as part of the characteristics of each model.
腰痛是导致残疾的主要原因，给全球医疗系统带来了巨大的社会经济负担。椎间盘退变是下腰痛的主要原因，尽管近年来已开发出旨在使椎间盘实现完全功能恢复的再生疗法，但目前尚无用于椎间盘再生的可商购、获批的设备或疗法。在这些新方法的开发过程中，出现了多种机械刺激和临床前评估模型，包括使用微流控技术的细胞研究、结合生物反应器和机械测试装置的器官研究，以及在各种大小动物身上进行的测试。这些方法具备不同的能力，无疑改善了这些再生疗法的临床前评估，但研究环境中的挑战以及与非代表性机械刺激和不现实测试条件相关的妥协仍有待解决。在本综述中，首先评估了用于测试椎间盘再生方法的理想椎间盘模型的特征。介绍了迄今为止在机械负荷刺激下从细胞、器官和整体椎间盘模型中获得的关键经验教训，以及基于与人类椎间盘环境（生物学和力学）的生理相似性以及每种方法可能的反馈和输出测量结果，每种模型的优缺点。从简化的细胞模型转向器官和整体方法时，复杂性增加，导致模型的可控性降低，但能更好地反映生理环境。尽管成本、时间和伦理限制取决于每种方法，但它们会随着模型复杂性的增加而上升。这些限制作为每种模型特征的一部分进行了讨论和权衡。
