Hydrogels of halogenated Fmoc-short peptides for potential application in tissue engineering

Molecular hydrogels formed by Fmoc-short peptides have been demonstrated to be a class of promising scaffolds/carrier for in vitro cell cultures/drug delivery. In this paper, we firstly studied the gelation property of Fmoc-halogenated phenylalanine and found that the halogenated compounds had better gelation properties than the Fmoc-phenylalanine in aqueous solutions. The most efficient gelator is Fmoc-4-fluoro-phenylalanine, which can gel PBS buffer solution at the minimum gelation concentration of 0.15 wt%. All of the hydrogels formed by halogenated or non-halogenated Fmoc-phenylalanine were characterized by SEM and fluorescence spectrometer. But unfortunately, they were not suitable for NIH 3T3 cell culture. Based on these information and the fact that arginine-glycine-aspartic acid (RGD) peptide could promote cells adhesion and division, we then synthesized a Fmoc-peptide (Fmoc-fFfFGRGD) based on the best gelator of 4-fluoro-phenylalanine (fF) and the cell adhesion peptide of RGD. We observed the formation of molecular hydrogels from Fmoc-fFfFGRGD and the hydrogels could promote NIH 3T3 cell adhesion and proliferation efficiently. This study provides useful information about the gelation property of peptides containing halogenated phenylalanine and the hydrogels reported in this paper had potentials to be used as materials for tissue engineering and drug delivery.