Cell functions such as proliferation, migration, and differentiation are key physiological processes that are influenced by the physiochemical extracellular environment. We report on the effect of three-dimensional (3D) scaffold modulus on human bone marrow stromal cell (hBMSC) differentiation. hBMSCs underwent osteogenic differentiation in polyethylene glycol (PEG) hydrogels of all moduli independent of modulus (300-fold range from 0.2 kPa to 59 kPa) in the absence of osteogenic differentiation supplements. However, osteogenic differentiation was enhanced that was accentuated in gels of higher moduli. Introducing soluble Arginine-Glycine-Aspartate-Serine (RGDS) peptide to blockind integrin receptors inhibited osteogenesis, demonstrating that matrix-integrin ligation in the scaffolds wais required for modulusaterial-drivenirected hBMSC osteogenic differentiation in 3D. Disruption of canonical mechanosensing elements that have been identified from 2D culture such as actin filaments, microtubules, myosin II motor contraction, and RhoA kinase (ROCK) did not abrogate hBMSC osteogenic differentiation in 3D. These data suggest show that increasing hydrogel modulus enhanced that osteogenic differentiation of hBMSCs in 3D scaffolds but that hBMSCs doid not use the same mechanosensing pathways that have been identified are involved in 2D culture.
Citation: Journal of Cell Biology
Pub Type: Journals
3D culture, bone marrow stromal cell, cytoskeleton, hydrogels, matrix modulus