Control of Dissipation Sources: A Central Aspect for Enhancing the Mechanical and Mechanobiological Performances of Hydrogels

Development of mechanically durable and biologically inductive hydrogels is a major challenge for load-bearing applications such as engineered cartilage. Dissipative capacity of articular cartilage is central to its functional behavior when submitted to loading. While fluid frictional drag is playing a significant role in this phenomenon, the flow-dependent source of dissipation is mostly overlooked in the design of hydrogel scaffolds. Herein, we propose an original strategy based on the combination of fluidic and polymeric dissipation sources to simultaneously enhance hydrogel mechanical and mechanobiological performances. The nondestructive dissipation processes were carefully designed by hybrid cross-linking of the hydrogel network and low permeability of the porous structure. It was found that intrachain and pore water distribution in the porous hydrogels improves the mechanical properties in high water fractions. In contrast to widely reported tough hydrogels presenting limited load support capability at low strain values, we obtained stiff and dissipative hydrogels with unique fatigue behavior. We showed that the fatigue resistance capability is not a function of morphology, dissipation level, and stiffness of the viscoelastic hydrogels but rather depends on the origin of the dissipation. Moreover, the preserved dissipation source under mechanical stimulation maintained a mechanoinductive niche for enhancing chondrogenesis owing to fluid frictional drag contribution. The proposed strategy can be widely used to design functional scaffolds in high loading demands for enduring physiological stimuli and generating regulatory cues to cells.