Extracellular matrix formation in self-assembled minimalistic bioactive hydrogels based on aromatic peptide amphiphiles

The hitherto inconsistency in clinical performance for engineered skin drives the current development of novel cell-scaffolding materials; one challenge is to only extract essential characteristics from the complex native ECM (extracellular matrix) and incorporate them into a scaffold with minimal complexity to support normal cell functions. This study involved small-molecule-based bioactive hydrogels produced by the co-assembly of two aromatic peptide amphiphiles: Fmoc-FF (Fluorenylmethoxycarbonyl-diphenylalanine) and Fmoc-RGD (arginine-glycine-aspartic acid). Three-dimensionally cultured human dermal fibroblasts deposited dense ECM networks including fibronectin and collagen I within the hydrogels in a 14-day culture. The fibroblasts organized the fibrous ECM and contracted the gel without differentiating into myofibroblasts. The stiffness of the cell-gel constructs increased dramatically due to ECM formation and gel contraction. This created an economical biomimetic model-scaffold to further understand skin reconstruction in vitro and supplied a design pathway to create versatile cell-scaffolds with varied bioactivities and simplicity.