TABLE 1.

Comparison of models used for studying intervertebral disc degeneration.

Model type	Species used	Degeneration induction methods	Advantages	Limitations	References
In vitro	Human/Animal disc cells (2D and 3D cultures)	Mechanical stress, Enzymes, Cytokines (biochemical), Hybrid (mechanical + biochemical)	Cost-effective, high-throughput, controlled conditions, ethical	Does not replicate IVD’s full complexity (e.g., avascularity, hypoxia, ECM structure)	(Rivera et al., 2022; Lazaro-Pacheco et al., 2023; Cao et al., 2021; Marinkovic et al., 2016; Vinken and Blaauboer, 2017; An and Masuda, 2006)
Ex vivo	Mouse, Rat, Rabbit, Bovine, Ovine, Caprine, Porcine, Human (cadaveric)	Proinflammatory cytokines, Mechanical injury, Degenerative loading, Enzymes	Preserves native disc structure and environment, reduces animal use, physiologically relevant	No systemic circulation, difficult to mimic low-nutrient conditions	(Salzer et al., 2023; Tang et al., 2022; McDonnell and Buckley, 2021b)
In vivo	Rodents, Rabbits, Dogs, Sheep, Pigs, Goats, Non-human primates	Surgical injury, Needle puncture, Enzymes, Mechanical loading	Replicates systemic interactions (vascular, immune), long-term assessment, clinically relevant biomechanics	High cost, ethical concerns, interspecies differences	(Tang et al., 2022; Poletto et al., 2022; Goel et al., 2020; Ribitsch et al., 2020; Kiani et al., 2022)