Highly-regulated signals surrounding stem cells, such as growth factor signals and matrix mechanical stiffness, have been implicated in modulating stem cell proliferation and maturation. However, tight control of proliferation and lineage commitment signals is rarely achieved during growth outside the body, since the spectrum of biochemical and mechanical signals that govern stem cell self-renewal and maturation are not fully understood. Therefore, stem cell control can potentially be enhanced through the development of material platforms that more precisely orchestrate the presentation of the aforementioned signals to stem cells.

We exploit the physical and chemical properties of hydrogels (polymers containing a significant volume of water) to mimic the native extracellular matrix surrounding mammalian cells. Using a biomimetic hydrogel, we define a robust synthetic and fully mechanically and chemically defined platform to regulate stem cell number and differentiation for the culture of adult neural stem cells. The synthetic hydrogel material properties, such as ligand type, ligand surface density, and stiffness (i.e., complex modulus), are quantitatively controlled and characterized. In this work, hydrogels modified with two cell-binding ligands, CGGNGEPRGDTYRAY from bone sialoprotein [bsp-RGD(15)] and CSRARKQAASIKVAVSADR from laminin [lam-IKVAV(19)], were assayed for their ability to regulate self-renewal and differentiation in a dose-dependent manner. Hydrogels with bsp-RGD(15) supported both self-renewal and differentiation above 5.3 pmol.cm^-2, whereas hydrogels with lam-IKVAV(19) failed to support stem cell adhesion and did not influence early differentiation. For hydrogels with bsp-RGD(15), we also explore the effects of hydrogel stiffness on neural stem cell self-renewal and differentiation. This platform is highly tunable and could potentially be used to translate in vitro control of stem cells to an implantable biomaterial that can be harnessed for tissue regeneration.