Combined Flexion, Torsion and Compression Drive Distinct Intervertebral Disc Failure Mechanisms Under Asymmetric, High‐Cycle Loading

Background: Recent advancements in next-generation bioreactors have substantially improved the simulation of complex, detrimental spinal mechanics in ex vivo intervertebral disc models. This study investigated intervertebral disc responses to combined flexion, torsion, and static compression. A range of loading frequencies, magnitudes, and patterns was applied to identify conditions that contribute to disc degeneration under complex motion. Methods: Twelve bovine coccygeal intervertebral discs (mean age 9 months) were subjected to three distinct loading regimes, with four samples per condition. Static compression of 0.1 MPa was combined with: (1) symmetrical 3° flexion/extension and 2° torsion, (2) symmetrical 6° flexion/extension and 4° torsion, and (3) asymmetrical 6° flexion and 4° torsion. Loading frequencies and durations ranged from 0.2 Hz for 1 h in symmetrical loading to 1 Hz for 2 h in asymmetrical loading over a 14-day period. Structural integrity, cell viability, tissue composition, and molecular responses were evaluated using histology, biochemical assays, and gene expression analysis. Results: < 0.01) and delamination on the compressed side. This structural damage occurred in AF regions with high cell viability (81% ± 17%), whereas significantly reduced cell viability was observed in the inner AF (30% ± 33%) and nucleus pulposus (28% ± 35%). Conclusions: Under conditions of asymmetrical and more frequent loading, complex motion involving flexion, torsion, and compression led to structural damage in the outer disc regions and promoted cell death in inner regions. These region-specific responses suggest the independent development of distinct failure mechanisms contributing to disc degeneration. They also underscore the importance of developing targeted strategies that address both structural integrity and cellular resilience in degeneration models and therapeutic interventions.