Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels

Mesenchymal stem cell (MSC) osteogenic differentiation requires scaffolds to support multiple stages of growth and differentiation signals. Fluorenyl-9-methoxycarbonyl diphenylalanine (Fmoc-FF) peptides self-assemble to create 3D nanofibers. Here, we cultured MSC in 2D and 3D Fmoc-FF layers to suppo...

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Main Authors: Faye Fouladgar, Robert Powell, Vishalakshi Irukuvarjula, Akhila Joy, Xiao Li, Neda Habibi
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:OpenNano
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352952025000040
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author Faye Fouladgar
Robert Powell
Vishalakshi Irukuvarjula
Akhila Joy
Xiao Li
Neda Habibi
author_facet Faye Fouladgar
Robert Powell
Vishalakshi Irukuvarjula
Akhila Joy
Xiao Li
Neda Habibi
author_sort Faye Fouladgar
collection DOAJ
description Mesenchymal stem cell (MSC) osteogenic differentiation requires scaffolds to support multiple stages of growth and differentiation signals. Fluorenyl-9-methoxycarbonyl diphenylalanine (Fmoc-FF) peptides self-assemble to create 3D nanofibers. Here, we cultured MSC in 2D and 3D Fmoc-FF layers to support their osteogenic differentiation. The stiffness of the hydrogels was tunable between 100 and 10,000 Pa which allows precise modulation of the cellular microenvironment. Scaffold stiffness impacted cell viability which softer scaffolds (100 Pa) favored higher viability. MSC formed spheroids in 3D hydrogel and showed spread morphology in 2D overlayers. Our results demonstrate that the Fmoc-FF 3D cultures significantly enhanced osteogenic differentiation, as evidenced by increased calcium deposition, elevated phosphatase activity, and the secretion of osteocalcin. We propose that the peptides provide integrin-binding sites that activate a cytoplasmic feedback loop essential for differentiation. These findings suggest that self-assembled Fmoc-FF peptide hydrogels, is a promising platform for bone tissue engineering applications.
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publisher Elsevier
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series OpenNano
spelling doaj-art-6ae829f872314ee5b83e216d2f86fd092025-02-06T05:12:27ZengElsevierOpenNano2352-95202025-03-0122100235Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogelsFaye Fouladgar0Robert Powell1Vishalakshi Irukuvarjula2Akhila Joy3Xiao Li4Neda Habibi5Department of Biomedical Engineering, University of North Texas, TX, USADepartment of Biomedical Engineering, University of North Texas, TX, USADepartment of Biomedical Engineering, University of North Texas, TX, USADepartment of Material Science & Engineering, University of North Texas, TX, USADepartment of Material Science & Engineering, University of North Texas, TX, USADepartment of Biomedical Engineering, University of North Texas, TX, USA; Corresponding author at: Nanomedicine Lab, Department of Biomedical Engineering, The University of North Texas, a Carnegie R1 Institution, Discovery Park, Office: K240E, USA.Mesenchymal stem cell (MSC) osteogenic differentiation requires scaffolds to support multiple stages of growth and differentiation signals. Fluorenyl-9-methoxycarbonyl diphenylalanine (Fmoc-FF) peptides self-assemble to create 3D nanofibers. Here, we cultured MSC in 2D and 3D Fmoc-FF layers to support their osteogenic differentiation. The stiffness of the hydrogels was tunable between 100 and 10,000 Pa which allows precise modulation of the cellular microenvironment. Scaffold stiffness impacted cell viability which softer scaffolds (100 Pa) favored higher viability. MSC formed spheroids in 3D hydrogel and showed spread morphology in 2D overlayers. Our results demonstrate that the Fmoc-FF 3D cultures significantly enhanced osteogenic differentiation, as evidenced by increased calcium deposition, elevated phosphatase activity, and the secretion of osteocalcin. We propose that the peptides provide integrin-binding sites that activate a cytoplasmic feedback loop essential for differentiation. These findings suggest that self-assembled Fmoc-FF peptide hydrogels, is a promising platform for bone tissue engineering applications.http://www.sciencedirect.com/science/article/pii/S2352952025000040Human mesenchymal stem cells (hMSCs)Fmoc-FF peptide hydrogelOsteogenic Differentiation
spellingShingle Faye Fouladgar
Robert Powell
Vishalakshi Irukuvarjula
Akhila Joy
Xiao Li
Neda Habibi
Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels
OpenNano
Human mesenchymal stem cells (hMSCs)
Fmoc-FF peptide hydrogel
Osteogenic Differentiation
title Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels
title_full Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels
title_fullStr Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels
title_full_unstemmed Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels
title_short Osteogenic differentiation of mesenchymal stem cells in cell-laden culture of self-assembling peptide hydrogels
title_sort osteogenic differentiation of mesenchymal stem cells in cell laden culture of self assembling peptide hydrogels
topic Human mesenchymal stem cells (hMSCs)
Fmoc-FF peptide hydrogel
Osteogenic Differentiation
url http://www.sciencedirect.com/science/article/pii/S2352952025000040
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