Figure 3.

Biomimetic strategies for exploiting heparan sulfate proteoglycans and their role in stem cell neurogenesis. Strategy (1) Exogenous HS. Heparin is a highly sulfated analog of HS that promotes growth factor activity such as stabilizing the binding of FGF2 to FGF receptor (FGFR). Strategy (2) Heparin-conjugate. Heparin is linked to various biomaterials to enhance its ability to mediate growth factor and receptor interactions (FGF2 activity in this example). For example, in the affinity-based delivery system (Willerth et al., 2008) heparin is bound to both a bidomain peptide linked to fibrin scaffolding and heparin-binding growth factor (i.e., FGF2). This technique harnesses the ability of heparin to bind growth factors, prevent degradation and potentiate receptor binding via a controlled release mechanism. Strategy (3) Synthetic glycopolymer. HS derivatives/synthetic HS are introduced to the cell surface via lipid or protein anchors, mimicking the role of HS in mediating growth factor signaling (e.g., FGF2 signaling). These strategies target heparan sulfate and growth factor interactions. In FGF2 signaling, extracellular signal-regulated kinases (Erk1/2) controls cellular proliferation and differentiation. Affinity-based delivery system sketch is modified from Willerth et al. (2008).