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.