Short-Term Dynamic Unloading of Bovine Tail Discs in Culture Partially Mitigates Induced Degeneration After...

Intervertebral disc (IVD) degeneration is driven by a vicious circle of interrelated biological and biomechanical factors. Dynamic unloading, defined as dynamic partial decompression, promotes water and metabolite flow, which is essential for IVD homeostasis. However, the mechanobiological effects of unloading remain poorly understood. IVD organ cultures offer a valuable model for studying IVD degeneration and regeneration at the molecular level. This study investigated the biological and biomechanical effects of induced degeneration and the subsequent short-term dynamic unloading of bovine tail IVDs in a bioreactor culture system.

We applied a one-strike degenerative trigger on Day 0 and assessed its immediate effects after 1 day of culture under bioreactor loading (Timepoint 1). The impact of dynamic unloading for three additional days (Timepoint 2) was evaluated in comparison to continued loading. We evaluated biological outcomes, namely cell viability, gene expression, water/sulfated glycosaminoglycan (sGAG) ratio, and sGAG release. Mechanical readouts included disc height, slope of the elastic zone, area under the curve, and neutral zone characteristics.

On Timepoint 1, we demonstrated degeneration in the nucleus pulposus with altered viability, increased inflammatory and catabolic gene expression, elevated sGAG release, a decreased slope of the elastic zone, and an increased area under the curve. On Timepoint 2, we noticed a sustained degenerative cascade in both degeneration groups. However, unloading showed a trend towards partial mitigation of the induced degeneration with decreased iNOS and TRPV4 expression, an increased water/sGAG ratio, reduced sGAG release, and recovery of the disc height.

This first ex vivo study on unloading mechanobiology of bovine degenerated IVDs unveils encouraging preliminary insights. The findings suggest potential benefits of unloading and, more broadly, therapeutic movement as regenerative strategies for degenerated IVDs. These results underscore the need for further studies and encourage research combining mechanical and biological approaches in organ culture models.