This study investigates the role of degradation-mediated cellular traction in directing the fate of human mesenchymal stem cells (hMSCs) within covalently crosslinked hyaluronic acid (HA) hydrogels. The researchers found that hMSC differentiation is influenced by the ability of cells to degrade the hydrogel matrix and generate traction, rather than cell morphology or matrix mechanics. hMSCs in hydrogels with equivalent elastic moduli exhibited high or low degrees of cell spreading and traction, leading to osteogenesis or adipogenesis, respectively. Delayed secondary crosslinking reduced hydrogel degradation, suppressed traction, and switched hMSC fate from osteogenesis to adipogenesis without altering cell morphology. Inhibiting tension-mediated signaling mimicked the effects of delayed secondary crosslinking, while upregulating tension induced osteogenesis even in restrictive conditions. These findings highlight the importance of cell-generated tension and the type of hydrogel used in regulating hMSC fate.This study investigates the role of degradation-mediated cellular traction in directing the fate of human mesenchymal stem cells (hMSCs) within covalently crosslinked hyaluronic acid (HA) hydrogels. The researchers found that hMSC differentiation is influenced by the ability of cells to degrade the hydrogel matrix and generate traction, rather than cell morphology or matrix mechanics. hMSCs in hydrogels with equivalent elastic moduli exhibited high or low degrees of cell spreading and traction, leading to osteogenesis or adipogenesis, respectively. Delayed secondary crosslinking reduced hydrogel degradation, suppressed traction, and switched hMSC fate from osteogenesis to adipogenesis without altering cell morphology. Inhibiting tension-mediated signaling mimicked the effects of delayed secondary crosslinking, while upregulating tension induced osteogenesis even in restrictive conditions. These findings highlight the importance of cell-generated tension and the type of hydrogel used in regulating hMSC fate.