Ultrashort Peptide Hydrogels Display Antimicrobial Activity and Enhance Angiogenic Growth Factor Release by Dental Pulp Stem/Stromal Cells.

Recent studies on peptide hydrogels have shown that ultrashort peptides (<8 amino acids) can self-assemble into hydrogels. Ultrashort peptides can be designed to incorporate antimicrobial motifs, such as positively charged lysine residues, so that the peptides have inherent antimicrobial characteristics. Antimicrobial hydrogels represent a step change in tissue engineering and merit further investigation, particularly in applications where microbial infection could compromise healing. Herein, we studied the biocompatibility of dental pulp stem/stromal cells (DPSCs) with an ultrashort peptide hydrogel, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), where the epsilon () amino group forms part of the peptide bond rather than the standard amino grouping. We tested the antimicrobial properties of NapFFKK-OH in both solution and hydrogel form against , and and investigated the DPSC secretome in hydrogel culture. Our results showed NapFFKK-OH hydrogels were biocompatible with DPSCs. Peptides in solution form were efficacious against biofilms of and , whereas hydrogels demonstrated antimicrobial activity against and . Using an angiogenic array we showed that DPSCs encapsulated within NapFFKK-OH hydrogels produced an angiogenic secretome. These results suggest that NapFFKK-OH hydrogels have potential to serve as novel hydrogels in tissue engineering for cell-based pulp regeneration.