Bioinspired supramolecular nanofiber hydrogel through self-assembly of biphenyl-tripeptide for tissue engineering

Supramolecular nanofiber peptide assemblies had been used to construct functional hydrogel biomaterials and achieved great progress. Here, a new class of biphenyl-tripeptides with different C-terminal amino acids sequences transposition were developed, which could self-assemble to form robust supramolecular nanofiber hydrogels from 0.7 to 13.8 kPa at ultra-low weight percent (about 0.27 wt%). Using molecular dynamics simulations to interrogate the physicochemical properties of designed biphenyl-tripeptide sequences in atomic detail, reasonable hydrogen bond interactions and FF brick (phenylalanine-phenylalanine) promoted the formation of supramolecular fibrous hydrogels. The biomechanical properties and intermolecular interactions were also analyzed by rheology and spectroscopy analysis to optimize amino acid sequence. Enhanced L929 cells adhesion and proliferation demonstrated good biocompatibility of the hydrogels. The storage modulus of BPAA-AFF with 10 nm nanofibers self-assembling was around 13.8 kPa, and the morphology was similar to natural extracellular matrix. These supramolecular nanofiber hydrogels could effectively support chondrocytes spreading and proliferation, and specifically enhance chondrogenic related genes expression and chondrogenic matrix secretion. Such biomimetic supramolecular short peptide biomaterials hold great potential in regenerative medicine as promising innovative matrices because of their simple and regular molecular structure and excellent biological performance.

Automated summary

A new class of biphenyl-tripeptides capable of self-assembling into robust supramolecular nanofiber hydrogels was developed. Molecular dynamics simulations revealed that reasonable hydrogen bond interactions and the presence of FF brick promoted the formation of the hydrogels. Rheology and spectroscopy analysis were used to analyze the biomechanical properties and intermolecular interactions of the hydrogels, and optimize the amino acid sequence. The results demonstrated the good biocompatibility and biological activity of these supramolecular nanofiber hydrogels, making them promising for applications in regenerative medicine.