Biomimetic interfacial interpenetrating polymer networks control neural stem cell behavior

Highly-regulated signals surrounding stem cells, such as growth factors at specific concentrations 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 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 signal presentation to stem cells. Using a biomimetic interfacial interpenetrating polymer network (IPN), we define a robust synthetic and highly-defined platform for the culture of adult neural stem cells. IPNs 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. IPNs with >5.3 pmol/cm(2) bsp-RGD(15) supported both self-renewal and differentiation, whereas IPNs with lam-IKVAV(19) failed to support stem cell adhesion and did not influence differentiation. The IPN platform is highly tunable to probe stem cell signal transduction mechanisms and to control stem cell behavior in vitro.