Multicomponent Dipeptide Supramolecular Hydrogels as Fibronectin-Mimetic Biomaterials

摘要

Self-assembled supramolecular peptide hydrogels are important biomaterials that have been designed as matrices for tissue engineering and regenerative medicine [1-4]. Hydrogels derived from low molecular weight dipeptides or functionalized amino acids are a subset of self-assembled peptide hydrogels that have garnered significant recent interest [5-7]. Serious effort has been directed toward engineering low molecular weight hydrogelators that rival peptides in terms of their emergent viscoelastic and biochemical properties. Biochemical cell signaling motifs are often incorporated into supramolecular peptide hydrogels to facilitate cell adhesion, migration, and differentiation. The fibronectin-derived Arg-Gly-Asp (RGD) motif has been frequently incorporated into these types of materials to enable cell adhesion by interacting with integrin receptors. Herein, we discuss two-component supramolecular hydrogels that functionally bind cell surface integrins in a fibronectin-like manner without the explicit display of the RGD peptide [8]. These hydrogels are composed of Fmoc-3F-Phe-Asp-OH (1) and Fmoc-3F-Phe-Arg-NH2 (2) dipeptides (Figure 1) that coassemble to form a fibril network. These fibrils display Asp and Arg at the surface to spatially mimic the Asp and Arg residues in the RGD motif. NIH 3T3 fibroblast cells adhere to the hydrogel surface via integrin binding in a demonstration of the fibronectin-like biochemical behavior of these materials.