INTERVERTEBRAL DISC MECHANOBIOLOGY: INSIGHTS AND INCONSISTENCIES FROM WHOLE-ORGAN BIOREACTOR STUDIES

No conflicts of interest. Sources of funding: EPSRC Doctoral Landscape Award Studentship. Background Poor intervertebral disc (IVD) health is a major contributor to low back pain and disability worldwide. Whole-organ bioreactors provide a platform to investigate IVD mechanobiology by replicating physiological loading, bridging the gap between cell culture models and animal studies, reducing animal use, and enabling cost-effective pre-clinical evaluation of interventions and regenerative strategies. Activities of daily living subject the IVD to complex loading in all six axes, but most whole-organ bioreactors are limited to applying simplified loading regimes in one or two axes. Furthermore, there is a lack of standardisation in bioreactor test protocols, resulting in substantial variability in applied load type, magnitude, duration, and IVD preparation and species. Methods This work aimed to evaluate previous IVD bioreactor studies to provide a better understanding of how loading influences cell viability and gene expression. Results Of the studies included, most reported no significant change in 15 commonly evaluated genes. When differences were identified, collagens I and II were more frequently downregulated in the annulus fibrosus, particularly under low-magnitude axial compression, whereas nucleus pulposus responses remained inconsistent across magnitudes and durations. A high variability in cell viability was observed across studies. Although lower loads often resulted in higher viability, the protocols typically employed shorter daily loading durations than higher-magnitude diurnal regimes, which limits direct comparisons. Conclusion This work highlights challenges in comparing IVD bioreactor studies and underscores limitations imposed by the absence of standardised practices. By identifying key trends and gaps, it supports the development of standardised loading protocols to strengthen mechanobiological insight and translational impact.