The control of stem cell morphology and differentiation by hydrogel surface wrinkles

In this study, we investigated human mesenchymal stem cell (hMSC) interactions with uniform hydrogels and hydrogels with lamellar or hexagonal surface wrinkles to elucidate our ability to control hMSC morphology and differentiation. Wrinkled hydrogels were prepared from photocurable poly(2-hydroxyethyl methacrylate) (PHEMA) precursor solutions containing ethylene glycol dimethacrylate as a crosslinker, using depth-wise gradients in crosslinking and subsequent buckling with swelling to generate wrinkles. A replica molding process was used to fabricate a series of gels with uniform mechanics, but altered surface wrinkle size and shape. We found that hMSCs attached to lamellar wrinkles spread by taking the shape of the pattern, exhibit high aspect ratios, and differentiate into an osteogenic lineage. In contrast, cells that attached inside the hexagonal patterns remain rounded with low spreading and differentiate into an adipogenic lineage. This work aids in the development of material-based cell culture and scaffold systems to direct stem cell differentiation.