Does viscoelasticity of a Hydrogel-cell construct affect ECM production?

Intervertebral disc (IVD) degeneration is one of the prevailing medical concern and actual health cost. Industries and academic institutions research for therapeutic solutions going from drugs to complete and partial arthroplasty devices as well as engineered tissues. Most research focus on the nucleus pulposus (NP) of the IVD because it is believed that, in the degeneration process, the NP is the scene of the first (irreversible) biochemical and mechanical changes. Mechanical, biochemical, nutritional and genetic factors may induce the degenerative process. Authors agree that (dynamic) mechanical stimuli are essential to preserve the integrity of the NP tissue. Indeed, sustained static loading and joint immobilization are proven to accelerate tissue degeneration. One possible explanation is that dynamic stimuli are required to transport (by convection) macromolecules, whereas smaller molecules are solely driven by passive diffusion. Another explanation is the requirement of direct cell-solid and/or cell-fluid interactions, namely mechanotransduction. In reality, both mechanisms are believed to influence tissue maintenance and should be considered evenly. It is, however, difficult to find a quantitative variable that unifies both theories. Viscoelasticity is the result of imperfect processes in which energy is dissipated. These imperfections arise from microstructural interactions and internal transport phenomena. Integrated, they result in time dependent and observable macroscopic behaviour. Although, interactions between phases are probably dominant, it makes sense to assume that cell-phase interactions are proportionally related. Therefore, investigating correlations between viscoelastic properties of the NP with cell synthesis may provide an experimental and theoretical mean to investigate the effect of dynamic mechanical stimuli on living tissues. The objective of this project is to verify this hypothesis on a hydrogel-cell construct model. Because the following step is to localize the viscoelastic description, extracellular matrix production is to be assessed with a 3D spatial resolution.