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

Abstract

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.

Reverse thermo-responsive hydrogels prepared from Pluronic F127 and gelatin composite materials

“…The hMSCs are multipotent stromal cells that can differentiate into a variety of cell types, such as adipocytes, chondrocytes, osteoblasts and so on. 37 Next, the biocompatibility of hydrogels of A1-A3 and B1-B3 on hMSCs were evaluated by WST-1 assay (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt). 38 Human MSCs were cultured for 2 days with the extraction medium of hydrogels of A1-A3 as well as B1-B3 and subjected for the cell viability experiments.…”

Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models

“…[ 272 ] FF bearing a 9‐fluorenylmethyloxycarbonyl group (Fmoc‐FF, being F phenylalanine) is the most studied in cell culture applications, because it can self‐assemble under physiological conditions. [ 273,274 ] Interestingly, it is possible to modify hydrogels stiffness by altering the C‐termini group, the aromatic amino acid, the peptide sequence or its charge. Also, Fmoc‐RGD can be added to the hydrogel to improve cell attachment.…”

“…Also, Fmoc‐RGD can be added to the hydrogel to improve cell attachment. [ 273,274 ] For example, hydrogels can be obtained by mixing two Fmoc‐dipeptides with opposite charge on the terminal residue (Fmoc‐YD and Fmoc‐YK) ( Figure a–e). This modification improved the mechanical properties and allowed its bioprinting through a droplet‐based 3D printing methodology.…”

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

“…MSCs afford beneficial effects in animal models of stroke [103][104][105][106]122 Increasing translational potential of in vivo stroke models for testing MSC efficacy and safety…”