Exploiting the Biophysical Cues toward Dual Differentiation of hMSC's within Geometrical Patterns

A wide variety of cues from the extracellular matrix (ECM) have been known to affect the differentiation of stem cells in vivo. In particular, the biophysical cues and cell shape have been known to affect the stem cell function, yet very little is known about the interplay between how these cues control differentiation. For the first time, by using photolithography to pattern poly(ethylene glycol) (PEG), patterns of square and triangular geometries were created, and the effect of these structures and the biophysical cues arising were utilized to differentiate cells into multiple lineages inside a same pattern without the use of any adhered protein or growth factors. The data from these studies showed that the cells present at the edges were well elongated, exhibit high aspect ratios, and differentiated into osteogenic lineage, whereas the cells present at the center exhibit lower aspect ratio and were primarily adipogenic lineage regardless of the geometry. This was correlated to the higher expression of focal adhesion proteins at the edges, the expression of which have been known to affect the osteogenic differentiation. By showing MSC lineage commitment relationships due to physical signals, this study highlights the importance of these cues and cell shape in further understanding stem cell behavior for tissue engineering applications.