Small Peptide-Based Hydrogels: Monitoring Stiffness and Self-Assembly Kinetics by Means of Oscillatory Rheology

The response of selected FMOCdipeptides to pH and ionic strength has been studied by oscillatory rheology coupled to microscopy. The gelation rate was proportional to that of protonation of the dipeptide carboxylic group. The ionic strength had also an effect on the gelation kinetics and morphology of the gel obtained. INTRODUCTION Hydrogels are an important class of biomaterials because they resemble the extracellular matrix (ECM) of the body and show biocompatibility, thus offering scaffolds for tissue engineering and providing matrices for drug delivery. Recently, stimuli-responsive hydrogelators have received much attention in drug/protein delivery. They can release entrapped molecules in response to a stimulus caused by environmental changes such as ionic strength, pH, enzymatic action. In several cases such as tumours, inflammatory tissues, and the phagolysosomes of antigen presenting cells, the drug delivery sites are acidic in nature and a “smart” hydrogel for selective delivery of the drugs would swell or degrade as the local pH lowers. For this purpose, several biocompatible pHresponsive hydrogelators have been synthesized from peptide-based molecules. Several studies have shown that dipeptides coupled to a fluorenylmethoxycarbonyl (Fmoc) moiety were gelled using a pH trigger, such that the sodium salt of the Fmoc-dipeptide (which is soluble) is converted to the acid form (which gels) by a drop in pH. As protonation occurs, hydrogen-bonds form and the dipeptides assemble from dissolved molecules via micellar structures to crystals and fibrils . Together with hydrogen bonding other mechanisms that depend on the solution ionic strength, such as the loss of hydrophobic association and the creation of ion-bridges, are likely to influence the selfassembly process. In the present study the effect of the pH and ionic strength on gelation are studied for three model FMOCdipeptides. The kinetics of gelation are investigated by means of oscillatory rheometry. This and the measured gel strength are then correlated to its microstructure.