Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Development of Self-Assembled Peptide Hydrogels Containing Matrix-Metalloproteinase Degradable Motifs for 3D Lung Cancer Models(Royal Society of Chemistry, 2026) Tarim, Burcu Sirma; Tamburaci, Sedef; Top, AybenHydrogel-forming peptides, including matrix metalloproteinase (MMP)-degradable motifs, have been employed to investigate cell-extracellular matrix interactions in vitro. However, their potential in 3D cancer models has been explored only in a few studies. In this study, we used modified MMP-2 degradable motifs (VSLRA or ASLRA) in the design of EDP1 (RVSLRADARVSLRADA) and EDP2 (RASLRADARASLRADA) peptide hydrogelators. The peptides self-assembled into nanofibrillar hydrogels with storage moduli between similar to 300 and similar to 400 Pa. MMP-2 degradation properties of the peptides were confirmed, and a slightly higher MMP-2 responsiveness of the EDP1 hydrogel was observed. The hydrogels were used in the encapsulation of A549 lung adenocarcinoma cancer cells and MRC-5 human lung fibroblast cells. The designed hydrogels supported the proliferation of these cells with high viability and induced cluster formation of encapsulated A549 cells similar to that observed with the RADA hydrogel. However, the hydrogel network structure affected the morphology of the migrated cells in the absence of curcumin. The addition of curcumin decreased the migration and invasion of A549 cells, resulting in a round cell morphology independent of the hydrogel matrices. Anticancer drug tests indicated that cell viability after drug treatment was higher in the 3D hydrogels than in 2D cultures. It was also confirmed that the combinational therapy of doxorubicin and curcumin decreased the cell proliferation and colonization to a greater extent compared to doxorubicin monotherapy. Thus, the hydrogels developed in this study can be used for 3D cancer models or other tissue engineering applications as an alternative to the RADA hydrogel by exploiting the MMP-2 degradation properties.Article Citation - WoS: 2Citation - Scopus: 2Integration of Leu-Asp Cell Attachment Motif Into Self-Assembling Peptide Sequences for Nanofibrillar Hydrogel Formation in Wound Healing(Amer Chemical Soc, 2025) Tarim, Burcu Sirma; Sırma Tarım, Burcu; Tamburaci, Sedef; Top, Ayben; Uysal, Berk; Top, AybenFunctionalizing peptide sequences with cell adhesion motifs enhances their cellular bioactivity. Numerous studies have focused on incorporating the Arg-Gly-Asp (RGD) motif into peptide hydrogels; however, the integration of other bioactive domains has yet to be comprehensively investigated. In this study, one of the essential fibronectin-derived cell-binding domains, Leu-Asp-Val (LDV), was integrated into the self-assembling peptide to obtain extracellular matrix (ECM)-mimetic nanofibrillar hydrogelators. IBP1A (NH2-KLDVKLDVKLKV-CONH2) and IBP1B (NH2-KLDVKLDVKLDV-CONH2) peptides were designed accordingly. These peptides self-assemble into hydrogels in phosphate-buffered saline (PBS) at pH 7.4 and deionized water at neutral pH with storage modulus values between similar to 200 and similar to 2000 Pa. Flow curves and the cyclic strain sweep data confirmed that the hydrogels have shear thinning, injectability, and self-healing properties. Flexible nanofibrillar morphology was observed in the TEM images. Nanofibril widths of IBP1A and IBP1B networks were measured as 8.2 +/- 1.1 and 4.5 +/- 0.8 nm, respectively. In vitro tests were also conducted to evaluate these peptides in wound healing applications. The IBP1A peptide with a +3 charge at neutral pH exhibited modest antibacterial activity against Gram (+) and Gram (-) bacteria. In vitro cell culture experiments show that the IBP1A and IBP1B hydrogels promoted the growth of fibroblast cells and glycosaminoglycan secretion compared with the KLDL12 control peptide, which does not contain the LDV motif. The designed hydrogels induced cell attachment within 72 h by altering the cell morphology similar to their natural 3D microenvironment, whereas cells exhibited spindle-like morphology on the KLDL12 hydrogel and tissue culture polystyrene (TCP). Moreover, IBP1B accelerated in vitro wound healing by facilitating fibroblast migration. These results suggest that these bioactive injectable peptide hydrogels have potential in wound healing and skin tissue regeneration.Article Poly(Ethylene Glycol)-Keratin Hydrogels Prepared Via Thiol-Maleimide Reaction(Polymer Soc Korea, 2025) Yalcin, Damla; Top, AybenThe mechanical properties of hydrogels have a profound effect on cellular responses in tissue engineering applications. In this study, poly(ethylene glycol)-keratin (PEG-KRTN) hydrogels with tunable mechanical properties were prepared by varying molar mass of the maleimide functionalized PEG in the thiol-maleimide chemistry. Reduced keratins were reacted with PEG-maleimides having 2000 Da and 6000 Da molar masses. Viscoelastic and physiochemical properties and cytocompatibility of these hydrogels were tested. Storage modulus values were obtained as 2613 +/- 254 Pa and 1313 +/- 345 Pa for PEG2000-KRTN and PEG6000-KRTN hydrogels, respectively. Strain sweep data indicate that the linear viscoelastic region (LVER) of the PEG6000-KRTN hydrogel spans up to 40% strain value, whereas it is limited to 10% critical strain for the PEG2000-KRTN hydrogel. PEG6000-KRTN hydrogel presented higher swelling ratios and porosity. CCK-8 test showed that both hydrogels promoted the proliferation of L929 mouse fibroblast cells and, hence, can be applied in soft tissue engineering.Article Evaluation of Partially Reduced Keratins Extracted From Wool Fibers as a Hydrogel Forming Biomaterial(inst Tecnologia Parana, 2024) Yalcin, Damla; Top, AybenIn this study, it was aimed to prepare low-cost hydrogel from reduced keratin. Keratin proteins were obtained from Merino wool via three extraction methods. In the first method, keratins were reduced using sodium sulfide. In the second method, keratins extracted with the first method were precipitated with HCl. Urea, EDTA, and sodium sulfide were used in the third method. Extraction yields of method 1, method 2, and method 3 were determined as 44 +/- 2, 27 +/- 1, and 42 +/- 2 %, respectively. For all extraction methods, the average value of the free thiol amounts was obtained as 0.06 +/- 0.02 mmol SH/g keratin. A considerable portion of the highly polydisperse keratins was separated between similar to 40 kDa and similar to 60 kDa in the SDS-PAGE gel, and this fraction corresponds to alpha-keratin proteins with low sulfur content. A strong band at similar to 1654 +/- 1 cm(-1) detected in the FTIR spectra of the keratins confirms mainly alpha-helical secondary structure. The self- standing hydrogel was obtained upon incubating 15 wt. % keratin solution at 37 degrees C. Storage modulus and loss modulus of the hydrogel were determined as 1.3 +/- 0.08 kPa and 0.1 +/- 0.015 kPa, respectively. The keratin hydrogel is not cytotoxic to L929 mouse fibroblast cells, suggesting that this affordable hydrogel can be applied as a drug delivery/encapsulation system and in wound healing.Article Citation - WoS: 5Citation - Scopus: 5Novel Biopolymer-Based Hydrogels Obtained Through Crosslinking of Keratose Proteins Using Tetrakis(hydroxymethyl) Phosphonium Chloride(Springer, 2022) Yalçın, Damla; Top, AybenMerino wool obtained from the Karacabey region of Turkey was solubilized using peracetic acid oxidation. The wool and extracted wool proteins (keratose) were characterized using SEM, XRD, TGA, and FTIR analyses. SDS-PAGE result of the keratose indicated diffusive bands were populated between ~ 40 and ~ 55 kDa, corresponding to low-sulfur content α-keratose proteins. Chemically crosslinked hydrogels were prepared using the keratose and tetrakis(hydroxymethyl) phosphonium chloride (THPC). Storage moduli of the hydrogels prepared at 1:1, 1:2, and 1:4 keratose to THPC reactive group ratios were measured as 63 ± 22, 291 ± 21, and 804 ± 53 Pa, respectively. Crosslinking degrees of the hydrogels also affected the secondary structures of the keratose films obtained from the drying of the hydrogels. The hydrogel with the highest crosslinking density (1:4 gel) exhibited the lowest swelling ratio, whereas the one with the lowest crosslinking density (1:1 gel) disintegrated in deionized water within less than 6 h. CCK-8 tests using L929 mouse fibroblast cells showed that all the hydrogels promoted cell proliferation. These results suggest THPC crosslinked hydrogels prepared at the millimolar THPC concentrations are biocompatible scaffolds, which can be utilized in drug delivery and tissue engineering applications. Graphical abstract: [Figure not available: see fulltext.]Article Citation - WoS: 3Citation - Scopus: 4Photocatalytic and Optical Properties of Zinc Oxide Structures Prepared at Different Urea Concentrations(Serban Solacolu Foundation, 2020) Uysal, Berk; Şen, Selin; Top, AybenIn this study, ZnO samples were synthesized using zinc acetate and urea with a method containing sonication, sol-gel transition and calcination steps. Urea to zinc acetate mole ratio values were changed as 0, 0.5, 1, and 2 and corresponding calcined samples were denoted as UZ-0, UZ-0.5, UZ-1, and UZ-2, respectively. Scanning electron microscopy (SEM) images indicated globular and rod-like structures. Aspect ratios of the nanorods increased as urea to zinc acetate ratio increased from 0 to 1 whereas nanoparticles with sizes of 70 +/- 20 nm were observed for UZ-2 sample. Brunauer, Emmett and Teller (BET) surface area values of the samples varied between 9 and 25 m(2)/g and increased as initial urea amount increased. Band gap energies of the samples ranged between 3.24 and 3.29 eV. Four major peaks at about 400, 420, 480 and 530 nm with different intensities were observed in the photoluminescence (PL) spectra of the samples. All the samples removed rhodamine B by both adsorption and photodegradation. The highest visible light induced photodegradation rate was exhibited by UZ-2 sample having the highest surface area and it is attributed to superior charge separation properties of this sample under visible light.Article Citation - WoS: 1Citation - Scopus: 1Potansiyel Doksorubisin Taşıyıcı Sistemi Olarak Peg-endozom Parçalayıcı Peptit Konjugatının Değerlendirilmesi(Gazi Üniversitesi, 2020) Şen, Selin; Top, AybenIn this study, it was aimed to develop a doxorubicin (DOX) carrier system based on a PEGylated TAT-derived cell penetrating peptide (G(2)RQR(3)QR(3)G(2)S) and to investigate drug release, self-assembly and stability properties of the carrier system. In the preparation of the drug delivery system, denoted as mPEG-peptide-oxime-DOX, methoxypolyethylene glycol (mPEG) with M-n=1900 Da was used. DOX was attached to the mPEG-peptide carrier system via acid cleavable oxime bond. Control drug delivery system, lack of the peptide (mPEG-oxime-DOX) was also synthesized to assess the effect of the peptide on the physicochemical and DOX release properties of the carrier system. mPEG-oxime-DOX exhibited a pH programmed DOX release with respective % DOX release values of similar to 68% and similar to 28% at pH 5.0 and at pH 7.4 at the end of 54 h. For the mPEG-peptide-oxime-DOX, on the other hand, quite low DOX release (similar to 10-15 %) was observed for both pH values suggesting possible interactions between DOX and the peptide. Initial median size value (D50) of the mPEG-oxime-DOX was measured as similar to 24 nm, independent of pH. However, for the mPEG-peptide-oxime-DOX, quite lower D50 values (similar to 3 nm and similar to 6 nm at pH 5.0 and pH 7.4, respectively) were obtained due to the repulsions between the arginines in the peptide sequence. Sizes of both drug delivery systems, tended to increase upon incubation at physiological conditions for 1 day suggesting that longer PEG chains should be used to enhance the stability of the mPEG-peptide-oxime-DOX and mPEG-oximeDOX systems.Article Citation - WoS: 4Citation - Scopus: 4Optical and Photocatalytic Properties of Zno and Zns Structures Formed as Controlled Calcination Products of L-Cysteine Assisted Aqueous Precipitation(Elsevier, 2020) Şen, Selin; Top, AybenZnO and ZnS structures were obtained by the calcination of the aqueous precipitation products of Zn(NO3)2, NaOH and L-cysteine (Cys). Initial Cys:Zn molar ratios were changed as 0.1:1, 0.5:1, 1:1 and 1.5:1. All the precursors were transformed into ZnO upon calcination at 700 °C. ZnS structures were obtained by calcining the precursors prepared at the Cys:Zn ratios of 1 and 1.5 at 350 °C. In addition to changing chemical composition of the precipitation products, calcination temperature and initial Cys:Zn ratio also affected morphology, surface area, photoluminescence and photocatalytic properties of the final products. Free exciton energy values of the ZnO samples were observed to be between 3.29 eV and 3.35 eV. PL spectra of the ZnO samples indicated blue and green emission centers. Zinc interstitials (Zni), revealed by the blue emissions in the PL spectra were also confirmed by Auger Zn L3M4.5M4.5 spectra. The samples calcined at 350 °C removed rhodamine B mainly by adsorption. All the samples calcined at 700 °C successfully degraded the dye under UV light. Among the samples calcined at 700 °C, ZnO sample prepared at Cys:Zn = 0.5, which has the highest surface area and unique photoluminescence spectrum exhibited the fastest photodegradation rate. © 2020 Elsevier LtdArticle Citation - WoS: 24Citation - Scopus: 26Self-Assembly Behavior of the Keratose Proteins Extracted From Oxidized Ovis Aries Wool Fibers(Elsevier Ltd., 2019) Pakkaner, Efecan; Yalçın, Damla; Uysal, Berk; Top, AybenWater soluble keratose proteins were obtained from an Ovis Aries wool using peracetic acid oxidation. The wool samples and the extracted keratose proteins were characterized by using FTIR, XRD, SEM and TGA techniques. Fractions of alpha-keratose (MW = 43-53 kDa) along with protein species with molecular weights between 23 kDa and 33 kDa were identified in the SDS-PAGE analysis result of the extracted protein mixture. DLS and AFM experiments indicated that self-assembled globular nanoparticles with diameters between 15 nm and 100 nm formed at 5 mg/ml keratose concentration. On the other hand, upon incubation of 10 w % keratose solutions at 37 degrees C and 50 degrees C, interconnected keratose hydrogels with respective storage modulus (G') values of 0.17 +/- 0.03 kPa and 3.7 +/- 0.5 kPa were obtained. It was shown that the keratose hydrogel prepared at 37 degrees C supported L929 mouse fibroblast cell proliferation which suggested that these keratose hydrogels could be promising candidates in soft tissue engineering applications. (C) 2018 Elsevier B.V. All rights reserved.Article Citation - WoS: 12Citation - Scopus: 12Peg and Peg-Peptide Based Doxorubicin Delivery Systems Containing Hydrazone Bond(Springer Verlag, 2018) Balcı, Beste; Top, AybenmPEG and mPEG-peptide based drug delivery systems were prepared by conjugating doxorubicin (DOX) to these carrier molecules via hydrazone bond. The peptide, AT1, with a sequence of CG3H6G3E served as mPEG and doxorubicin attachment site. Histidines were incorporated to the sequence to improve pH responsiveness of the carrier molecule. Hydrodynamic diameters (mean sizes) of mPEG-based drug delivery system (mPEG-HYD-DOX) were measured as 9 ± 0.5 and 7 ± 0.5 nm at pH 7.4 and pH 5.0, respectively. Mean size of the aggregates of the peptide containing drug delivery system, mPEG-AT1-DOX, was determined as 12 ± 2 nm at neutral pH. At pH 5.0, on the other hand, mPEG-AT1-DOX exhibited a size distribution between 20 and 100 nm centered at about 40 nm. Comparison of % DOX release values of the drug delivery systems obtained at pH 7.4 and pH 5.0 indicated that mPEG-AT1-DOX has enhanced pH sensitivity. DOX equivalent absolute IC50 values were obtained as 0.96 ± 0.51, 21.9 ± 5.9, and 5.55 ± 0.75 μg/mL for free DOX, mPEG-HYD-DOX, and mPEG-AT1-DOX, respectively. Considering more pronounced pH sensitivity and cytotoxicity of mPEG-AT1-DOX, the use of both pH responsive functional groups and acid cleavable chemical bond between the carrier molecule and drug can be a promising approach in the design of drug delivery systems for cancer therapy.