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 surface are found to be able to migrate into the gel to form 3D distribution and further undergo differentiation, primarily directed by the cell-adhesive motifs within the gel. Such a TGase-based strategy for reconstituting bioactive hydrogels can be readily applied to any other self-assembling peptides and active motifs given rational molecular design, thus showing broad-spectrum application potentials in biological and biomedical fields.