Dual-crosslinkable alginate hydrogel with dynamic viscoelasticity for chondrogenic and osteogenic differentiation of mesenchymal stem cells.

Tissue engineering presents an advanced approach for cartilage and bone tissue repair, with cells serving as a crucial component of the treatment process. The viscoelasticity, a defining fundamental mechanical property, significantly influences cellular behavior. The majority of current research has primarily focused on comparing static elastic and viscoelastic hydrogels with varying stress relaxation rates, while neglecting the inherent dynamic viscoelastic properties of native tissues. Herein, we developed a dynamic viscoelastic hydrogel system employing modified sodium alginate hydrogels to explore the impact of the transfer of viscoelasticity and elastic mechanical properties on the behavior and fate of mesenchymal stem cells (MSCs). The results demonstrated that a viscoelastic environment facilitates greater cell proliferation and spreading. Moreover, extended exposure to the viscoelastic environment resulted in significantly enhanced secretion of osteogenic/chondrogenic extracellular matrix (ECM), upregulates differentiation-specific gene expression, and supports nuclear localization of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). This study elucidates the mechanical microenvironment required for MSC differentiation, enriching the theoretical foundation for the design of optimized scaffold in cartilage and bone tissue engineering applications.