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      Fmoc-FF and hexapeptide-based multicomponent hydrogels as scaffold materials

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          Abstract

          Short peptides or single amino acids are interesting building blocks for fabrication of hydrogels, frequently used as extracellular matrix-mimicking scaffolds for cell growth in tissue engineering.

          Abstract

          Short peptides or single amino acids are interesting building blocks for fabrication of hydrogels, frequently used as extracellular matrix-mimicking scaffolds for cell growth in tissue engineering. The combination of two or more peptide hydrogelators could allow obtaining different materials exhibiting new architectures, tunable mechanical properties, high stability and improved biofunctionality. Here we report on the synthesis, formulation and multi-scale characterization of peptide-based mixed hydrogels formed by the low molecular weight Fmoc-FF (N α-fluorenylmethyloxycarbonyl diphenylalanine) hydrogelator and of the PEG 8-(FY)3 hexapeptide, containing three repetitions of the Phe-Tyr motif and a PEG moiety at its N-terminus. Mixed hydrogels were also prepared by replacing PEG 8-(FY)3 with its analogue (FY)3, without the PEG moiety. Rheology analysis confirmed the improved mechanical features of the multicomponent gels prepared at two different ratios (2/1 or 1/1, v/v). However, the presence of the hydrophilic PEG polymeric moiety causes a slowing down of the gel kinetic formation (from 42 to 18 minutes) and a decrease of the gel rigidity ( G′ from 9 to 6 kPa). Preliminary in vitro biocompatibility and cell adhesion assays performed on Chinese hamster ovarian (CHO) cells suggest a potential employment of these multicomponent hydrogels as exogenous scaffold materials for tissue engineering.

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          Most cited references38

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          Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution.

          H. Levine (1993)
          Thioflavine T (ThT) associates rapidly with aggregated fibrils of the synthetic beta/A4-derived peptides beta(1-28) and beta(1-40), giving rise to a new excitation (ex) (absorption) maximum at 450 nm and enhanced emission (em) at 482 nm, as opposed to the 385 nm (ex) and 445 nm (em) of the free dye. This change is dependent on the aggregated state as monomeric or dimeric peptides do not react, and guanidine dissociation of aggregates destroys the signal. There was no effect of high salt concentrations. Binding to the beta(1-40) is of lower affinity, Kd 2 microM, while it saturates with a Kd of 0.54 microM for beta(1-28). Insulin fibrils converted to a beta-sheet conformation fluoresce intensely with ThT. A variety of polyhydroxy, polyanionic, or polycationic materials fail to interact or impede interaction with the amyloid peptides. This fluorometric technique should allow the kinetic elucidation of the amyloid fibril assembly process as well as the testing of agents that might modulate their assembly or disassembly.
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            Common core structure of amyloid fibrils by synchrotron X-ray diffraction.

            Tissue deposition of normally soluble proteins as insoluble amyloid fibrils is associated with serious diseases including the systemic amyloidoses, maturity onset diabetes, Alzheimer's disease and transmissible spongiform encephalopathy. Although the precursor proteins in different diseases do not share sequence homology or related native structure, the morphology and properties of all amyloid fibrils are remarkably similar. Using intense synchrotron sources we observed that six different ex vivo amyloid fibrils and two synthetic fibril preparations all gave similar high-resolution X-ray fibre diffraction patterns, consistent with a helical array of beta-sheets parallel to the fibre long axis, with the strands perpendicular to this axis. This confirms that amyloid fibrils comprise a structural superfamily and share a common protofilament substructure, irrespective of the nature of their precursor proteins. Copyright 1997 Academic Press Limited.
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              Nanostructured Hydrogels for Three-Dimensional Cell Culture Through Self-Assembly of Fluorenylmethoxycarbonyl–Dipeptides

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                Author and article information

                Journal
                SMOABF
                Soft Matter
                Soft Matter
                Royal Society of Chemistry (RSC)
                1744-683X
                1744-6848
                January 16 2019
                2019
                : 15
                : 3
                : 487-496
                Affiliations
                [1 ]Department of Pharmacy
                [2 ]Research Centre on Bioactive Peptides (CIRPeB)
                [3 ]University of Naples “Federico II”
                [4 ]80134 Naples
                [5 ]Italy
                [6 ]Department of Oral Biology
                [7 ]The Goldschleger School of Dental Medicine
                [8 ]Sackler Faculty of Medicine
                [9 ]Tel Aviv University
                [10 ]Tel Aviv
                [11 ]Institute of Crystallography (IC)
                [12 ]CNR
                [13 ]70126 Bari
                Article
                10.1039/C8SM02366B
                30601569
                ec165273-d411-4db7-b6d2-256625406d0e
                © 2019

                http://rsc.li/journals-terms-of-use

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