Abstract
Hydrogels are useful delivery vehicles for therapeutic proteins. The ability to control the rate of protein release is paramount to a gel's utility and, in part, defines its clinical application. Electrostatic interactions made between encapsulated protein and a gel's network represents one modality in which protein motility can be controlled. For many gels this strategy works well under low ionic strength solution conditions, but dramatically less so in solutions of physiologically relevant ionic strength where electrostatic interactions are more effectively screened. Herein, we find that highly charged self-assembling peptides can be used to prepare fibrillar hydrogels of sufficient electropotential to allow electrostatic-based control over protein release under physiological buffer conditions. Rheology shows that proteins, differing significantly in their isoelectric point, can be directly encapsulated within negatively- or positively-charged peptide hydrogel networks during the peptide self-assembly event leading to gelation. Bulk adsorption studies coupled with transmission electron microscopy shows that electrostatic interactions drive the association of protein to oppositely charged fibrils in the final gel state, which in turn, dictates the diffusion and retention of these macromolecules in the hydrogel network.