Recent studies revealing stem cell behavior dependence on mechanical properties of a substrate has initiated the need to probe matrix mechanics and its influence on stem cell fate in a physiologically relevant three-dimensional (3D) microenvironment. We investigated the proliferative and osteogenic potentials of Wharton's jelly mesenchymal stem cells (WJMSCs) immobilized in alginate microspheres with respect to the mechanical properties of alginate hydrogels (1, 1.5 and 2% (w/v)) post incubation in a simulated in vivo environment. Compressive moduli, degradation profile, and swelling kinetics of the hydrogels varied proportionally with alginate concentration and with exposure to simulated conditions. Degradation profile and morphological analysis showed that hydrogels exhibiting high modulus (2% w/v) remained the most intact at the end of day 21. High cell viability in all conditions was observed throughout the culture period. Low-modulus hydrogels (1% w/v) facilitated proliferation of WJMSCs whereas high-modulus hydrogels demonstrated better osteogenic differentiation inferred by an up regulation of osteo-specific genes, expressions of osteocalcin, and quantification of calcium deposition. These findings present a step forward in the development of application-specific hydrogel matrices for stem cell-based tissue engineering.
