Growth Factor Binding\non Heparin Mimetic Peptide Nanofibers

Abstract

Immobilization of growth factors in scaffolds is important\nfor\ncontrolling their dose and bioactivity for regenerative medicine applications.\nAlthough numerous covalent and noncovalent immobilization strategies\nhave been proposed, better growth factor loading and dose control\ninside the scaffold is necessary. Nature of the binding site on the\ngrowth factor interacting with scaffold is critical for preserving\nand achieving maximal growth factor functionality, which has been\na relatively less emphasized issue in previous studies. We recently\nreported heparin mimetic peptide nanofibers, which mimic chemistry\nof heparan sulfates. Heparin mimetic nanofibers were shown to bind\nto vascular endothelial growth factor (VEGF) and direct endothelial\ncells to angiogenesis. Here, we further investigated interactions\nbetween heparin mimetic peptide nanofibers and growth factors. We\ntested bioactivity of the nanofiber bound growth factors in order\nto understand the potential use of these peptide nanofiber scaffolds\nas analogues of heparan sulfates. We observed that heparin mimetic\npeptide nanofibers demonstrate better binding profiles to VEGF, hepatocyte\ngrowth factor (HGF), and fibroblast growth factor-2 (FGF-2) than control\npeptide nanofibers. We also identified that the heparin-binding domain\nof VEGF is critical for its interaction with these nanofibers. However,\nthe heparin-binding site is not indispensable for binding of all growth\nfactors to nanofibers. We also showed that binding of growth factors\nto nanofibers does not cause any loss in bioactivity through in vitro\ncell culture assays with PC-12 cells. These results reveal that heparin\nmimetic peptide nanofibers can effectively mimic heparan sulfates\nin extracellular matrix and provide an optimal milieu for spatial\npresentation of important growth factors. These properties make peptide\nnanofiber scaffolds promising materials for regenerative medicine\napplications through efficient and precisely controlled growth factor\ndelivery.