Dipeptide Self-Assembled Hydrogels with Shear-Thinning and Instantaneously Self-Healing Properties Determined by Peptide Sequences.

Dipeptide self-assembled hydrogels have potential biomedical applications because of their great biocompatibility, bioactivity and tunable physicochemical properties, which can be modulated in molecular level by design of amino acid sequences. Herein, a series of dipeptides (Fmoc-FL, -YL, -LL and -YA) are designed to form shear-thinning hydrogels with self-healing and tunable mechanical properties by adjusting the synergetic effect of hydrophobic interactions (pi-pi stacking and hydrophobic effect) and hydrogen bonds of peptides through substitution of amino acid residues. The enhancement of hydrophobic interactions is a primary factor to promote mechanical rigidity of hydrogels, and strengthen of hydrogen bonds among molecules endows hydrogels with instantaneous self-healing property, which is supported by experimental studies (FTIR, CD, SEM, AFM and rheology) and molecular dynamic (MD) simulations. The injectable dipeptide hydrogels were certified as an ideal endoscopic submucosal dissection (ESD) filler to make operation convenient and secure in mice and living mini-pig's experiments with longer duration time, higher stiffness and lower inflammatory response compared with commercial clinical fillers.