Cartilaginous microtissues exhibit extreme resilience under compression with size-dependent mechanical properties.

Self-assembled cartilaginous microtissues provide a promising means of repairing challenging skeletal defects and connective tissues. However, despite their considerable promise in tissue engineering, the mechanical response of these engineered microtissues is not well understood. Here we examine the mechanical and viscoelastic response of progenitor cell aggregates formed from human primary periosteal cells and the resulting cartilaginous microtissues under large deformations as might be encountered in vivo. We find that the mechanical response of these tissues is strongly size dependent due to surface tension effects, with a scaling law for the Young's modulus of E ∝ D(m), where D is the diameter of the tissues, and m varies with the tissue type. Similar size effects are found to govern the interfacial surface tension and the viscosity. In addition, these microtissues are extremely resilient, as they sustain over 90 % of compressive strain without mechanical failure. Stress relaxation experiments reveal a fast stress dissipation at short time scale within a few seconds, followed by oscillations in measured stresses that depend on actomyosin contractility. In summary, these experiments reveal the remarkable and unanticipated resilience of cartilaginous microtissues under large mechanical strains, a property that may facilitate their use in a variety of tissue engineering applications. More broadly, our data highlight the importance of surface tensions in determining the mechanical properties of tissues on the micron and the mm length scales.