Browsing by Author "Ide, S."

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Open Access
Self-assembled peptide amphiphile nanofibers and PEG composite hydrogels as tunable ECM mimetic microenvironment
(American Chemical Society, 2015) Göktaş, Melis; Çınar, Göksu; Orujalipoor, I.; Ide, S.; Tekinay, Ayse B.; Güler, Mustafa O.
(Figure Presented). Natural extracellular matrix (ECM) consists of complex signals interacting with each other to organize cellular behavior and responses. This sophisticated microenvironment can be mimicked by advanced materials presenting essential biochemical and physical properties in a synergistic manner. In this work, we developed a facile fabrication method for a novel nanofibrous self-assembled peptide amphiphile (PA) and poly(ethylene glycol) (PEG) composite hydrogel system with independently tunable biochemical, mechanical, and physical cues without any chemical modification of polymer backbone or additional polymer processing techniques to create synthetic ECM analogues. This approach allows noninteracting modification of multiple niche properties (e.g., bioactive ligands, stiffness, porosity), since no covalent conjugation method was used to modify PEG monomers for incorporation of bioactivity and porosity. Combining the self-assembled PA nanofibers with a chemically cross-linked polymer network simply by facile mixing followed by photopolymerization resulted in the formation of porous bioactive hydrogel systems. The resulting porous network can be functionalized with desired bioactive signaling epitopes by simply altering the amino acid sequence of the self-assembling PA molecule. In addition, the mechanical properties of the composite system can be precisely controlled by changing the PEG concentration. Therefore, nanofibrous self-assembled PA/PEG composite hydrogels reported in this work can provide new opportunities as versatile synthetic mimics of ECM with independently tunable biological and mechanical properties for tissue engineering and regenerative medicine applications. In addition, such systems could provide useful tools for investigation of how complex niche cues influence cellular behavior and tissue formation both in two-dimensional and three-dimensional platforms.
Open Access
Supramolecular GAG-like self-assembled glycopeptide nanofibers Induce chondrogenesis and cartilage regeneration
(American Chemical Society, 2016) Yaylaci, U. S.; Ekiz, M. S.; Arslan, E.; Can, N.; Kilic, E.; Ozkan, H.; Orujalipoor, I.; Ide, S.; Tekinay, A. B.; Güler, Mustafa O.
Glycosaminoglycans (GAGs) and glycoproteins are vital components of the extracellular matrix, directing cell proliferation, differentiation, and migration and tissue homeostasis. Here, we demonstrate supramolecular GAG-like glycopeptide nanofibers mimicking bioactive functions of natural hyaluronic acid molecules. Self-assembly of the glycopeptide amphiphile molecules enable organization of glucose residues in close proximity on a nanoscale structure forming a supramolecular GAG-like system. Our in vitro culture results indicated that the glycopeptide nanofibers are recognized through CD44 receptors, and promote chondrogenic differentiation of mesenchymal stem cells. We analyzed the bioactivity of GAG-like glycopeptide nanofibers in chondrogenic differentiation and injury models because hyaluronic acid is a major component of articular cartilage. Capacity of glycopeptide nanofibers on in vivo cartilage regeneration was demonstrated in microfracture treated osteochondral defect healing. The glycopeptide nanofibers act as a cell-instructive synthetic counterpart of hyaluronic acid, and they can be used in stem cell-based cartilage regeneration therapies.
Open Access
Supramolecular nanostructure formation of coassembled amyloid inspired peptides
(American Chemical Society, 2016-06) Cinar, G.; Orujalipoor, I.; Su, C.-J.; Jeng, U.-S.; Ide, S.; Güler, Mustafa O.
Characterization of amyloid-like aggregates through converging approaches can yield deeper understanding of their complex self-assembly mechanisms and the nature of their strong mechanical stability, which may in turn contribute to the design of novel supramolecular peptide nanostructures as functional materials. In this study, we investigated the coassembly kinetics of oppositely charged short amyloid-inspired peptides (AIPs) into supramolecular nanostructures by using confocal fluorescence imaging of thioflavin T binding, turbidity assay and in situ small-angle X-ray scattering (SAXS) analysis. We showed that coassembly kinetics of the AIP nanostructures were consistent with nucleation-dependent amyloid-like aggregation, and aggregation behavior of the AIPs was affected by the initial monomer concentration and sonication. Moreover, SAXS analysis was performed to gain structural information on the size, shape, electron density, and internal organization of the coassembled AIP nanostructures. The scattering data of the coassembled AIP nanostructures were best fitted into to a combination of polydisperse core-shell cylinder (PCSC) and decoupling flexible cylinder (FCPR) models, and the structural parameters were estimated based on the fitting results of the scattering data. The stability of the coassembled AIP nanostructures in both fiber organization and bulk viscoelastic properties was also revealed via temperature-dependent SAXS analysis and oscillatory rheology measurements, respectively.
Open Access
Virus-like nanostructures for tuning immune response
(Nature Publishing Group, 2015) Mammadov R.; Cinar, G.; Gunduz, N.; Goktas, M.; Kayhan, H.; Tohumeken, S.; Topal, A. E.; Orujalipoor, I.; Delibasi, T.; Dana, A.; Ide, S.; Tekinay, A. B.; Güler, Mustafa O.
Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero-and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nucleasemediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.