Substance P-Derived Extracellular-Matrix-Mimicking Peptide Hydrogel as a Cytocompatible Biomaterial Platform

Self-assembled short peptide-based hydrogel platforms have become widely applicable biomedical therapeutic maneuvers for their soft, tunable architecture, which can influence cellular behavior and morphology to an inordinate extent. In this work, a short supramolecular hydrogelator peptide, substance P, has been designed and synthesized from the C terminus conserved "FFGLM" section of a biologically abundant neuropeptide by using a fusion approach. In addition, to incorporate a good hydrophobic-hydrophilic balance, the truncated pentapeptide segment was further C-terminally modified by the incorporation of an integrin-binding "RGD" motif. Thanks to its N-terminal Fmoc group, this octapeptide ensemble "FFGLMRGD" undergoes rapid self-assembly to give rise to an injectable, pH-responsive, hydrogel-based self-supporting platform that exhibited good cytocompatibility with the cultured mammalian cells under both 2D and 3D culture conditions without exerting any potent cytotoxic effect in a Live/Dead experiment. A rheological experiment demonstrated its hydrogel-like mechanical properties, including thixotropicity. The atomic force microscopy and field emission scanning electron microscopy images of the fabricated hydrogel show a tangled fibrous surface topography owing to the presence of the N-terminal Fmoc-FF residue. Furthermore, an in-vitro scratch assay performed on fibroblast cell lines confirmed the wound-ameliorating potency of this designed hydrogel; this substantiates its future therapeutic prospects.