Stem cell‐derived 3D tissues such as spheroids are excellent models for investigating mechanisms of tissue formation and responses to physiological and mechanical cues. Neuronal spheroids, also known as neurospheres, have attracted particular interest. A lot is now known about the differentiation and maturation of neurospheres, as well as their responses to biochemical cues. However, understanding about their mechanical properties pales in comparison, which is all the more galling in light of newfound insights about how mechanical stimuli trigger the onset of neurodegenerative conditions. Herein, formative steps are taken to fill this knowledge gap. Neurospheres are generated from murine neural stem cells and are subjected to compressive forces. It is observed that neurospheres exhibit stress relaxation under static compression and viscoelastic behavior at low strains. The suitability of the Tatara model for characterizing the mechanical properties of neurospheres is also evaluated. The study is the first study of its kind to investigate the mechanical properties of in vitro 3D tissues. Moreover, the methodologies developed in the study can also be used to improve the quality and safety of cell and tissue biomanufacturing processes.
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