The role of mechanical hysteresis source in mechanical and mechanobiological performances of load-bearing biomaterials

Tissue engineering is a promising approach for articular cartilage regeneration as no satisfactory treatment is actually available for cartilage, partly due to the very limited self-healing capability of this tissue. To successfully induce a cartilaginous tissue formation, however, a variety of contributing factors either from a biological or engineering standpoint should be optimized. In particular, sufficient biophysical signals should be provided to promote the response of the spatially distributed cells in a biomimetic three dimensional (3D) scaffold. Given the significance of cartilage dissipative properties when it is submitted to loading, we hypothesized that hydrogels presenting adequate viscoelastic properties could provide a mechano-mimetic niche that would support chondrocyte precursors proliferation and differentiation. In addition, a preserved hysteresis source is an essential feature for a tough biomaterial with robust mechanical behavior. As a consequence, a carefully designed dissipative hydrogels might simultaneously enhance its mechanical and mechanobiological performances. Therefore, the development of mechanically and biologically functional hydrogels as model systems to study the mechanobiology of cartilage is the central aim of this thesis. Indeed, elucidating the aspects of cartilage mechanobiology can facilitate the clinical translation of engineered construct as the mechanical cues significantly influence the cells response. In parallel, temperature evolution due to the conversion of the dissipated energy to heat following cyclic loading brings new insights to interpret the effects of mechanical forces on the cells behavior. In this context, identifying the optimal thermo-mechanical stimulation of cells-laden hydrogel can positively contribute to the development of engineered cartilage. Given hydrogel as a biphasic material, it can dissipate the input mechanical energy via interstitial fluid frictional drag and macromolecular network resistance to deformation. These two fundamentally different physical mechanisms, which induce a mechanical hysteresis, can be controlled by the biphasic material’s permeability and by the composition of its network, respectively. Accordingly, we firstly developed an experimental method to directly measure the strain-dependent permeability of visco-porous hydrogels. Based on the correlation between the permeability-composition pair and the hydrogel dissipation, an original combination of flow-dependent and flow-independent dissipation source was proposed for the design of biomechanically functional hydrogels. In particular, a heteroporous yet low permeable, fatigue resistance hydrogel was developed via an hybrid crosslinking strategy presenting weak physical bonds and strong covalent bonds. We showed that hydrogels with the same level of stiffness and energy dissipation respond to fatigue loading in a significant different way, depending on their preserved or shrank hysteresis curves during cyclic loading. By developing a semi-inverse poro-viscoelastic model, we also showed that the load is partly carried by the solid phase in hybridly crosslinked hydrogel with low permeability thanks to the support of the pressurized fluid. Before evaluating the role of the dissipation mechanisms in chondrogenesis, we developed a reproducible cell seeding technique via a combination of computational and experimental approaches. In particular, the optimized compression release-induced suction