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

Najafi, Haniyeh; Tamaddon, Ali Mohammad; Abolmaali, Samira Sadat; Borandeh, Sedigheh; Azarpira, Negar

doi:10.1039/d0sm01299h

Cited by 15 publications

(19 citation statements)

References 57 publications

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“…The effect of Fmoc-RGD as a cell–matrix adhesion molecule was investigated by preparing Fmoc-FF hydrogels containing WJ-MSCs with various contents of Fmoc-RGD or the control sequence (Fmoc-RGE). WJ-MSCs were isolated, expanded, and characterized according to our previous report [ 25 ]. For cell encapsulation, a mixture containing an equal volume of Fmoc-dipeptide solution with cell suspensions was prepared in serum-free DMEM.…”

Section: Resultsmentioning

confidence: 99%

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Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury

et al. 2022

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Background Mesenchymal-based therapy has been utilized as a practical approach in the treatment of renal ischemia/reperfusion (I/R) injury. However, low cell retention and survival in the ischemic site have remained challenging issues. To bridge this gap, the integrin receptor-binding RGD peptide-functionalized, s-nitroso-n-acetyl penicillamine (SNAP)-loaded hydrogel was used to transplant Wharton's jelly-mesenchymal stem cells (WJ-MSCs). Methods Apart from physicochemical and rheological characterizations that confirmed entangled interlocking β-sheets with nanofibrous morphology, real-time RT-PCR, ROS production, serum biomarker concentrations, and histopathological alterations were explored in a mouse model to assess the therapeutic efficacy of formulations in the treatment of renal I/R injury. Results The RGD-functionalized Fmoc-diphenylalanine (Fmoc-FF + Fmoc-RGD) hydrogel supported the spread and proliferation of WJ-MSCs in vivo. Notably, intralesional injection of nitric oxide donor combined with the embedded WJ-MSCs caused superior recovery of renal I/R injury compared to free WJ-MSCs alone in terms of histopathological scores and renal function indices. Compared to the I/R control group, oxidative stress and inducible nitric oxide synthase (iNOS) expression biomarkers showed a significant decline, whereas endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression exhibited a significant increment, indicating regeneration of the injured endothelial tissue. Conclusion The findings confirmed that the hydrogels containing WJ-MSCs and nitric oxide donors can promote the regeneration of renal I/R injuries by increasing angiogenic factors and cell engraftment.

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Section: Resultsmentioning

confidence: 99%

“…Fmoc-FF (Chempep, USA) was synthesized through tert-butyl ester reaction chemistry, as reported elsewhere [ 25 ]. Briefly, 315 µl isobutyl chloroformate was added to the Fmoc-phenylalanine-OH (472 mg) solution in CHCl 3 under stirring.…”

Section: Methodsmentioning

confidence: 99%

Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury

et al. 2022

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“…Field Emission SEM Studies with the LP2 Peptide. To further visualize the supramolecular nanoscale morphology of assemblies of the LP2 peptide, field emission scanning electron microscopy (FESEM) studies 25,26 were performed with the LP2 peptide in Milli-Q water and images were captured. Prominent nano-globular assemblies of the LP2 were visible (Figure 3E).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Self-Assembling Nano-Globular Peptide from Human Lactoferrin Acts as a Systemic Enhancer of Bone Regeneration: A Novel Peptide for Orthopedic Application

Pal

Sayeed

Kumar

et al. 2021

ACS Appl. Mater. Interfaces

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A technology for systemic and repeated administration of osteogenic factors for orthopedic use is an unmet medical need. Lactoferrin (∼80 kDa), present in milk, is known to support bone growth. We discovered a lactoferrin-mimetic peptide, LP2 (an 18-residue fragment from the N-terminus of the N-lobe of human lactoferrin), which self-assembles into a nano-globular assembly with a β-sheet structure in an aqueous environment. LP2 is non-hemolytic and non-cytotoxic against human red blood cells and 3T3 fibroblasts, respectively, and appreciably stable in the human serum. LP2 through the bone morphogenetic protein-dependent mechanism stimulates osteoblast differentiation more potently than the full-length protein as well as the osteoblastic production of osteoprotegerin (an anti-osteoclastogenic factor). Consequently, daily subcutaneous administration of LP2 to rats and rabbits with osteotomy resulted in faster bone healing and stimulated bone formation in rats with a low bone mass more potently than that with teriparatide, the standard-of-care osteogenic peptide for osteoporosis. LP2 has skeletal bioavailability and is safe at the 15× osteogenic dose. Thus, LP2 is a novel peptide that can be administered systemically for the medical management of hard-to-heal fractures.

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“…Over the years, as more and more Fmoc-modified dipeptide hydrogelators were reported, such as Fmoc-Phe-Tyr ( Wang et al, 2008 ; Sadownik et al, 2011 ; Hughes et al, 2013 ), Fmoc-Phe-Leu ( Ren et al, 2020 ), Fmoc-Phe-Cys ( Wang and Chau, 2012 ), Fmoc-Phe-Val ( Najafi et al, 2021 ), Fmoc-Tyr-Ala ( Bai et al, 2014 ; Ren et al, 2020 ), Fmoc-Tyr-Ser ( Hughes et al, 2012 , 2013 ; Bai et al, 2014 ), Fmoc-Tyr-Thr ( Hughes et al, 2012 , 2013 ), Fmoc-Tyr-Asn ( Hughes et al, 2013 ), and Fmoc-Gly-Ser, which also self-assembled into fibrillar structures like Fmoc-Phe-Phe, the results indicated that the π–π and hydrophobic interactions of intermolecular Fmoc groups are the main driving forces in the self-assembly process of these systems. Moreover, double Fmoc group-containing dipeptide, Fmoc-Lys (Fmoc)-Asp, as an hydrogelator with the lowest CGC ever reported, 0.002 wt% (28.3 × 10 –6 M), was reported by Gazit and Wei et al ( Chakraborty et al, 2020 ).…”

Section: Cooh-terminal and N-terminal Modified Dipeptidementioning

confidence: 99%

Self-Assembly Dipeptide Hydrogel: The Structures and Properties

Zheng

et al. 2021

Front. Chem.

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Self-assembly peptide-based hydrogels are well known and popular in biomedical applications due to the fact that they are readily controllable and have biocompatibility properties. A dipeptide is the shortest self-assembling motif of peptides. Due to its small size and simple synthesis method, dipeptide can provide a simple and easy-to-use method to study the mechanism of peptides’ self-assembly. This review describes the design and structures of self-assembly linear dipeptide hydrogels. The strategies for preparing the new generation of linear dipeptide hydrogels can be divided into three categories based on the modification site of dipeptide: 1) COOH-terminal and N-terminal modified dipeptide, 2) C-terminal modified dipeptide, and 3) uncapped dipeptide. With a deeper understanding of the relationship between the structures and properties of dipeptides, we believe that dipeptide hydrogels have great potential application in preparing minimal biocompatible materials.

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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

Abstract: Fmoc-dipeptides are a class of short aromatic peptides featuring eminent supramolecular self-assembly, which is due to aromaticity of the Fmoc group that improves the association of peptide building blocks. This...

Cited by 15 publications

References 57 publications

Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury

Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury

Self-Assembling Nano-Globular Peptide from Human Lactoferrin Acts as a Systemic Enhancer of Bone Regeneration: A Novel Peptide for Orthopedic Application

Self-Assembly Dipeptide Hydrogel: The Structures and Properties

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