Self-Assembled Peptide-Based Hydrogels as Scaffolds for Proliferation and Multi-Differentiation of Mesenchymal Stem Cells

Fluorenyl-9-methoxycarbonyl (Fmoc)-diphenylalanine (Fmoc-FF) and Fmoc-arginine-glycine-­aspartate (Fmoc-RGD) peptides self-assemble to form a 3D network of supramolecular hydrogel (Fmoc-FF/Fmoc-RGD), which provides a nanofibrous network that uniquely presents bioactive ligands at the fiber surface for cell attachment. In the present study, mesenchymal stem cells (MSCs) in Fmoc-FF/Fmoc-RGD hydrogel increase in proliferation and survival compared to those in Fmoc-FF/Fmoc-RGE hydrogel. Moreover, MSCs encapsulated in Fmoc-FF/Fmoc-RGD hydrogel and induced in each defined induction medium undergo in vitro osteogenic, adipogenic, and chondrogenic differentiation. For in vivo differentiation, MSCs encapsulated in hydrogel are induced in each defined medium for one week, followed by injection into gelatin sponges and transplantation into immunodeficient mice for four weeks. MSCs in Fmoc-FF/Fmoc-RGD hydrogel increase in differentiation into osteogenic, adipogenic, and chondrogenic differentiation, compared to those in Fmoc-FF/Fmoc-RGE hydrogel. This study concludes that nanofibers formed by the self-assembly of Fmoc-FF and Fmoc-RGD are suitable for the attachment, proliferation, and multi-differentiation of MSCs, and can be applied in musculoskeletal tissue engineering. (Figure presented.).