Dissipation as variable in cartilage mechanobiology

Mechanobiology is the analysis of the role of mechanical forces in educing a molecular response in cells. Nowadays, mechanobiology may contribute to clinical progress. In particular, mechanical stimulation has been proposed to induce chondrogenesis in engineered cartilage constructs. However, the effects of mechanical stimuli on cell-scaffold constructs may vary substantially between different scaffolds. This advocates for the need to identify an overarching mechanobiological variable. We hypothesized that energy dissipation during dynamic loading could be such a variable. Dissipation would thus help in the engineering of cartilage constructs, but also would give insights on the cartilage mechanobiology in general. The goal of this thesis was to assess the effect of dissipation phenomena on chondrogenic expression during cyclic stimulation. We focused our work on three main aspects. First, we assessed the direct effect of mechanical dissipation on chondro-progenitor cells subject to cycling loading. Polymeric scaffolds showing different levels of dissipation for a same dynamic deformation were seeded with cells and were subject to cyclic unconfined compression. Chondrogenic markers were maximally expressed in scaffolds having the dissipation close to the dissipation of healthy human cartilage. Then, we quantified the cartilage self-heating due to dissipation with deformation calorimetry. We showed that dissipation was sufficient to rise the temperature in knee cartilage from 33°C to 37°C after 40 minutes of walking, assuming adiabatic conditions due to cartilage avascularity. On a cellular level, the 4°C temperature increase upregulated chondrogenic markers in human chondro-progenitors cells. Taken together, these results denoted the implication of cartilage dissipation in chondrogenic expression via self-heating. Finally, we developed a mathematical model allowing to calculate more precisely the cartilage temperature evolution due to dissipation by considering heat transfer from the cartilage. Limitations related to the assumption of cartilage adiabaticity were thus circumvented with the model. As well, the parameters appearing in the developed model were experimentally determined, in part thanks to in vivo MRI thermometry. The model predictions indicated that despite heat transfer, dissipation could still rise significantly the temperature in knee cartilage from 33°C to 36.7°C after one hour of walking in normal healthy human cartilage. Notably, lower dissipation of degenerated cartilage could not increase temperature to reach optimal values for the metabolism of extracellular matrix proteins, suggesting a link between dissipative properties of the cartilage and its homeostasis. We concluded that energy dissipation could be a quantitative measurement of different thermo-mechanical processes related to chondrocytes environment. In particular, dissipation could then be considered as a mechanobiological variable and may be essential for cartilage homeostasis.