Browsing by Subject "Growth factors"
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Item Open Access Affinity of glycopeptide nanofibers to growth factors and their effects on cells(Bilkent University, 2017-09) Haştar, NurcanThe development of scaffolds for growth factor delivery is a promising approach for tissue regeneration applications due to their crucial roles during regeneration. Growth factor secretion and interactions with glycosaminoglycans are essential steps for the regulation of cellular behavior. Therefore, glycosaminoglycan-mimetic scaffolds provide a great opportunity to modulate the effects of growth factor actions on cell fate. In this thesis, sugar-bearing peptide amphiphile molecules were characterized and tested for VEGF, FGF-2 and NGF affinity. ELISA-based affinity analyses revealed that glycopeptide nanofibers had high affinity to NGF; however, glycopeptides alone were not enough to interact efficiently with VEGF and FGF-2. Since VEGF and NGF contain heparin-binding domains, the addition of a sulfonated peptide amphiphile increased the affinity of the nanofiber network to these growth factors. Glycopeptide-sulfonate nanofibers were also found to promote in vitro tube formation through their VEGF and FGF-2 affinity. VEGF release profiles of HUVECs indicated that increasing concentration of VEGF may provide autocrine signaling and enhance tube formation without any exogenous pro-angiogenic factor addition. In addition, when NGF-responsive PC-12 cells were cultured on glycopeptide nanofibers, they extended their neurites to an extent comparable with a widely-used positive control molecule (poly-L-lysine). These results suggest that glycosaminoglycan-mimetic glycopeptide nanofiber networks can be used as efficient growth factor presentation platforms for tissue regeneration applications to induce angiogenesis or peripheral nerve regeneration.Item Open Access Effect of double growth factor release on cartilage tissue engineering(2013) Ertan, A.B.; Yilgor P.; Bayyurt, B.; Çalikoǧlu, A.C.; Kaspar Ç.; Kök F.N.; Kose G.T.; Hasirci V.The effects of double release of insulin-like growth factor I (IGF-I) and growth factor β1 (TGF-β1) from nanoparticles on the growth of bone marrow mesenchymal stem cells and their differentiation into cartilage cells were studied on PLGA scaffolds. The release was achieved by using nanoparticles of poly(lactic acid-co-glycolic acid) (PLGA) and poly(N-isopropylacrylamide) (PNIPAM) carrying IGF-I and TGF-β1, respectively. On tissue culture polystyrene (TCPS), TGF-β1 released from PNIPAM nanoparticles was found to have a significant effect on proliferation, while IGF-I encouraged differentiation, as shown by collagen type II deposition. The study was then conducted on macroporous (pore size 200-400μm) PLGA scaffolds. It was observed that the combination of IGF-I and TGF-β1 yielded better results in terms of collagen type II and aggrecan expression than GF-free and single GF-containing applications. It thus appears that gradual release of a combination of growth factors from nanoparticles could make a significant contribution to the quality of the engineered cartilage tissue. © 2011 John Wiley & Sons, Ltd.Item Open Access In situ functionalization of poly(hydroxyethyl methacrylate) cryogels with oligopeptides via β-Cyclodextrin–adamantane complexation for studying cell-instructive peptide environment(American Chemical Society, 2020) Luong, T. D.; Zoughaib, M.; Garifullin, Ruslan; Kuznetsova, S.; Güler, Mustafa O.; Abdullin, T. I.Oligopeptides are versatile cell modulators resembling pleiotropic activities of ECM proteins and growth factors. Studying the role of cellinstructive peptide signals within 3D scaffolds, yet poorly known, requires effective approaches to introducing bioactive sequences into appropriate materials. We synthesized RGD and GHK motif based peptides 1 and 2 linked to the terminal adamantyl group (Ad) and their fluorescent derivatives 3 and 4. Poly(hydroxyethyl methacrylate) (pHEMA) cryogels with additional PEG/β- cyclodextrin (CD) units were prepared as an inert macroporous scaffold capable to bind the adamantylated peptides via affinity CD-Ad complexation. According to toluidine blue staining, the CD moieties were effectively and stably incorporated in the pHEMA cryogels at nanomolar amounts per milligram of material. The CD component gradually increased the thickness and swelling ability of the polymer walls of cryogels, resulting in a noticeable decrease in macropore size and modulation of viscoelastic properties. The labeled peptides exhibited fast kinetics of specific binding to the CD-modified cryogels and were simultaneously immobilized by coincubation. The peptide loading approached ca. 0.31 mg per cm2 of cryogel sheet. A well-defined mitogenic effect of the immobilized peptides (2 < 1≪ 1 + 2) was revealed toward 3T3 and PC-12 cells. The synergistic action of RGD and GHK peptides induced a profound change in cell behavior/morphology attributed to a growth-factor-like activity of the composition. Altogether, our results provide an effective procedure for the preparation of CDmodified pHEMA cryogels and their uniform in situ functionalization with bioactive peptide(s) of interest and an informative study of cellular responses in the functionalized scaffolds