PH-responsive branched peptide amphiphile hydrogel designed for applications in regenerative medicine with potential as injectable tissue scaffolds

Nanofibrous materials have become an important component in the field of regenerative medicine. Due to their resemblance with extracellular matrix proteins, nanofibrous materials are capable of eliciting natural cell behaviors. One class of self-assembling molecules that forms nanofibers is peptide amphiphiles (PAs). The modularity of self-assembly affords the ability to tailor PA assemblies for specific applications through molecular design and mixing of different components. Illustrated here is an extended-micelle-forming PA synthesized in a branched architecture composed of histidine and serine amino acids conjugated to a palmitoyl tail. Using histidine residues as molecular switches, PA solutions are capable of transitioning from viscoelastic liquids in mildly acidic conditions to self-supporting hydrogels above pH 6.5. By modulating the concentration of the PAs, biocompatible hydrogels of 0.2-10 kPa were achieved. This PA hydrogel system is a potential candidate as an injectable three-dimensional tissue scaffold.