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

Abstract

AbstractSelf‐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.