Transglutaminase-Triggered Gelation and Functionalization of Designed Self-Assembling Peptides for Guiding Cell Migration

Due to the structural and compositional similarity to the extracellular matrix (ECM), self-assembling peptide hydrogels (SAPHs) have shown potential as three-dimensional (3D) scaffolds in regenerative medicine. However, how to fabricate SAPHs with controlled bioactivity for specific applications still remains greatly challenging. In this study, we develop a viable strategy to prepare bioactive SAPHs based on designed short amphiphilic peptides and cell-adhesive motifs, through the combination of enzymatic functionalization and gelation methods. Transglutaminase (TGase) can successfully catalyze the tethering of bioactive features onto the peptide nanofiber surface, and the TGase-meditated conjugation is found to rapidly trigger peptide gelation. Confocal microscopy indicates a uniform ligand distribution within the fibrous hydrogel, and mass spectrometry measurements reveal the involved enzymatic reactions and the gelation mechanism. Furthermore, the preosteoblast cells introduced on the bioactive gel sur...