| Summary: | Summary: Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing β1-integrin in embryonic cortical neurons. Furthermore, in adult neural stem cell culture, bifunctionalized gels promoted neurogenesis via the expansion of neurogenic clones. These data highlight the potential of synthetic matrices to steer stem and progenitor cell behavior via defined mechano-adhesive properties. : In this article, Farrukh and colleagues show that bifunctionalization of hydrogel substrates with polylysine and a 19-mer peptide containing the laminin motif IKVAV promotes neurogenesis from embryonic neuroblasts and adult neural stem cells. Neurogenesis and neurite outgrowth can be further optimized by adjusting gel stiffness in a cell-type-specific manner. Keywords: biomaterials, bioengineering, hydrogels, neural stem cells, cell differentiation, laminin, IKVAV, polylysine, β1-integrin, neurogenesis
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