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Structural, mechanical, and biological characterization of hierarchical nanofibrous Fmoc-phenylalanine-valine hydrogels for 3D culture of differentiated and mesenchymal stem cells

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Abstract

Fmoc-dipeptides are a class of short aromatic peptides featuring eminent supramolecular self-assembly, which is due to the aromaticity of the Fmoc group, which improves the association of peptide building blocks. This study aimed to introduce a new dipeptide hydrogel scaffold, Fmoc-phenylalanine-valine (Fmoc-FV), for 3D culture of various cells. Peptide hydrogel scaffolds were prepared by the pH-titration method in various concentrations and temperatures, and characterized by spectroscopic methods, including circular dichroism, attenuated total reflection FT-IR and fluorimetry. Mechanical behaviors such as thixotropy and temperature-sensitivity were investigated by oscillatory rheology. The Fmoc-FV hydrogels were then applied in 3D-culture of WJ-MSCs (mesenchymal stem cells), HUVECs (normal endothelial cells), and MDA-MB231 (tumor cell line) by live-dead fluorescence microscopy and Alamar blue viability assay experiments. The results confirmed that the β-sheet structure is principally interlocked by π–π stacking of the Fmoc groups and entangled nanofibrous morphologies as revealed by FE-SEM. Fmoc-FV self-assembly in physiologic conditions resulted in a thermo-sensitive and shear-thinning hydrogel. Notably, the Fmoc-FV hydrogel exhibited cell type-dependent biological activity, so higher cell proliferation was attained in HUVEC or MDA-MB231 cells than WJ-MSCs, indicating a possible need for incorporating cell-adhesion ligands in the Fmoc-FV hydrogel matrix. Therefore, the structural and biological properties of the Fmoc-dipeptide hydrogels are inter-related and can affect their applications in 3D cell culture and regenerative medicine.

Graphical abstract: Structural, mechanical, and biological characterization of hierarchical nanofibrous Fmoc-phenylalanine-valine hydrogels for 3D culture of differentiated and mesenchymal stem cells

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Supplementary files

Article information


Submitted
16 Jul 2020
Accepted
05 Sep 2020
First published
14 Sep 2020

Soft Matter, 2020, Advance Article
Article type
Paper

Structural, mechanical, and biological characterization of hierarchical nanofibrous Fmoc-phenylalanine-valine hydrogels for 3D culture of differentiated and mesenchymal stem cells

H. Najafi, A. M. Tamaddon, S. Abolmaali, S. Borandeh and N. Azarpira, Soft Matter, 2020, Advance Article , DOI: 10.1039/D0SM01299H

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