A temperature and ion dual responsive biphenyl-dipeptide supramolecular hydrogels as extracellular matrix mimic-scaffolds for cell culture application
Stimuli-responsive supramolecular hydrogels composed with aromatic short peptide gelators have arouse intensive attention in biomedicine field because of its stable chemical structure, simple and convenient synthetic route and intelligent response to external stimuli. In this paper, several dipeptides were coupled to biphenylacetic acid (BPAA) to generate aromatic short peptide compounds through the standard solid phase peptide synthesis. These BPAA-dipeptide compounds presented clearly different gelation behaviors from the generally employed Fmoc-dipeptide and Nap-dipeptide compounds, but only BPAA-diphenylalanine was able to form homogeneous and transparent hydrogels through temperature switch or ion induction. Utilizing the biphenyl group not only expanded the scope of aromatic molecules serving as building block of aromatic short peptide gelators but also demonstrated the critical role of aromatic molecules in self-assembling process. Moreover, the supramolecular hydrogels initiated by heating-cooling or salts addition could be exploited as extracellular matrix (ECM) mimic scaffolds to support the adhesive growth and proliferation of L929 cells in 2D/3D culture at physiological condition, demonstrating the potential applications in regenerative medicine.