Si<i>x</i>-Axis, Physiological Activity Profiles Create a More Challenging Cellular Environment in the Intervertebral Disc Compared to Single-Axis Loading

Bioreactors provide a valuable way to explore interactions between the mechanical and biological environments of the intervertebral disc (IVD), but the replication of ecologically valid loading protocols is a huge challenge. The aim of this study was to address this through the combination of time use survey data and six-axis load data from <i>in vivo</i> measurements during functional movements and activities of daily living to create population-based activity profiles, which were employed using a unique si<i>x</i>-axis bioreactor and a whole-organ bovine tail IVD model. The results of the study show that six-axis activity profiles create a more challenging environment compared to single-axis loading or unloaded controls, resulting in lower cell viability in both the nucleus pulposus and annulus fibrosus regions of the IVD. Additionally, the six-axis activity profile representing a more active lifestyle led to an even lower cell viability in the annulus fibrosus, which may be due to the increased strains in this region of the IVD during activities of daily living. These findings highlight the importance of considering a wide range of activities and lifestyles in the development and evaluation of regenerative therapies and preventative interventions for IVD, if they are to be successfully translated to the clinical setting.