Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 61Citation - Scopus: 64Electrospun Gelma Fibers and P(hema) Matrix Composite for Corneal Tissue Engineering(Elsevier Ltd., 2021) Arıca, Tuğçe A.; Güzelgülgen, Meltem; Yıldız, Ahu Arslan; Demir, Mustafa MuammerThe development of biocompatible and transparent three-dimensional materials is desirable for corneal tissue engineering. Inspired from the cornea structure, gelatin methacryloyl-poly(2-hydroxymethyl methacrylate) (GelMA-p(HEMA)) composite hydrogel was fabricated. GelMA fibers were produced via electrospinning and covered with a thin layer of p(HEMA) in the presence of N,N?-methylenebisacrylamide (MBA) as cross-linker by drop-casting. The structure of resulting GelMA-p(HEMA) composite was characterized by spectrophotometry, microscopy, and swelling studies. Biocompatibility and biological properties of the both p(HEMA) and GelMA-p(HEMA) composite have been investigated by 3D cell culture, red blood cell hemolysis, and protein adsorption studies (i.e., human serum albumin, human immunoglobulin and egg white lysozyme). The optical transmittance of the GelMA-p(HEMA) composite was found to be approximately 70% at 550 nm. The GelMA-p(HEMA) composite was biocompatible with tear fluid proteins and convenient for cell adhesion and growth. Thus, as prepared hydrogel composite may find extensive applications in future for the development of corneal tissue engineering as well as preparation of stroma of the corneal material. © 2020 Elsevier B.V.Article Citation - WoS: 5Citation - Scopus: 6Boosting Up Printability of Biomacromolecule Based Bio-Ink by Modulation of Hydrogen Bonding Pairs(Elsevier Ltd., 2020) Köksal, Büşra; Önbaş, Rabia; Başkurt, Mehmet; Şahin, Hasan; Arslan Yıldız, Ahu; Yıldız, Ümit HakanThis study describes low dose UV curable and bioprintable new bioink made of hydrogen bond donor-acceptor adaptor molecule 2-isocyanatoethyl methacrylate (NCO)modified gelatin (NCO-Gel). Our theoretical calculations demonstrate that insertion of 2-isocyanatoethyl methacrylate doubles the interaction energy (500 meV) between gelatin chains providing significant contribution in interchain condensation and self-organization as compared to methacrylic anhydride modified gelatin (GelMA). The NCO-Gel exhibits peak around 1720 cm?1 referring to bidentate hydrogen bonding between H-NCO and its counterpart O[dbnd]CN[sbnd]H. These strong interchain interactions drive chains to be packed and thereby facilitating UV crosslinking. The NCO-Gel is exhibiting a rapid, 10 s gelation process by the exposure of laser (3 W, 365 nm). The dynamic light scattering characterization also reveals that NCO-Gel has faster sol to gel transition as compared to GelMA depending on the UV curing time. The NCO-Gel was found to be more firm and mechanically strong that provides advantages in molding as well as bioprinting processes. Bioprinted NCO-Gel has shown sharp borders and stable 3D geometry as compared to GelMA ink under 10 s UV curing time. The cell viability tests confirm that NCO-Gel facilitates cell proliferation and supports cell viability. We foresee that NCO-Gel bioink formulation provides a promising opportunity when low dose UV curing and rapid printing are required. © 2020 Elsevier LtdArticle Citation - WoS: 14Citation - Scopus: 17Biocompatibility of Silicon Nitride Produced Via Partial Sintering & Tape Casting(Elsevier Ltd., 2021) Çeçen, Berivan; Topateş, Gülsüm; Kara, Aylin; Akbulut, Serdar Onat; Havıtçıoğlu, Hasan; Kozacı, Leyla DidemThe biocompatibility of silicon nitride ceramics was proven by several studies however this study is apart from the literature in the manner of production routes that are tape casting and partial sintering. We report the tape casting route was chosen and a porous structure was obtained by partial sintering technique. Tape casting brought a smooth surface to the samples. Density and pore size distribution analysis showed that the scaffolds have low density because of the porous structure. XRD and SEM analyses were carried out to reveal the phase and microstructural characteristics of porous ceramic samples. Static contact angle measurement was done for the characterization of the wettability of the scaffolds. It revealed that the surface of the scaffolds was highly hydrophilic which is a desirable characteristic for the protein and cell adhesion. The mechanical characteristics of the scaffolds were analyzed by compression tests. Human osteosarcoma cells were used for in vitro studies. Cell-proliferation and cytotoxicity were analyzed by WST-1 and LDH, respectively. The osteoblastic behavior of the cells on the surface of the scaffolds was identified by alkaline phosphatase activity. BCA analysis was used for total protein content. The BCA and ALP results showed an increasing trend which is directly correlated with cell proliferation. Cells on the surface of the silicon nitride scaffolds were visualized by SEM and fluorescence microscopy where the images supported the in vitro analysis. Therefore, porous silicon nitride scaffolds fabricated via tape casting and partial sintering were biocompatible and they are possible candidates as bone substitute elements. © 2020 Elsevier Ltd and Techna Group S.r.l.Article Citation - WoS: 5Citation - Scopus: 7Five New Cardenolides Transformed From Oleandrin and Nerigoside by Alternaria Eureka 1e1bl1 and Phaeosphaeriasp. 1e4cs-1 and Their Cytotoxic Activities(Elsevier Ltd., 2021) Karakoyun, Çiğdem; Küçüksolak, Melis; Bilgi, Eyüp; Doğan, Gamze; Çömlekçi, Yiğit Ege; Bedir, ErdalBiotransformation of oleandrin (1) and nerigoside (2) by endophytic fungi; Alternaria eureka 1E1BL1 and Phaeospheria sp. 1E4CS-1, has led to the isolation of five new metabolites (3, 5, 6, 7 and 8) together with a known compound (4). The structures of the biotransformation products were elucidated by 1D-, 2D NMR and HR-MS. Phaeospheria sp. mainly provided monooxygenation reactions on the A and B rings, whereas A. eureka afforded both monooxygenated and desacetylated derivatives of the substrates. Cytotoxic activity of the compounds was tested against a non-cancerous (HEK-293) and four cancer (PANC-1, MIA PaCa-2, DU 145 and A549) cell lines by MTT cell viability assay. All compounds were less cytotoxic than oleandrin, which had IC50 values ranging between 2.7 and 41.9 nM. Two of the monohydroxylated metabolites, viz. 7(?)-hydroxy oleandrin (3) and 1(?)-hydroxy oleandrin (7), were also potent with IC50 values from 18.45 to 39.0 nM, while desacetylated + monohydroxylated, or dihydroxylated products had much lower cytotoxicity. Additionally, the lesser activity of 2 and its metabolite (6) possessing diginose as sugar residue inferred that oleandrose moiety is important for the toxicity of oleandrin as well as hydrophobicity of the steroid core. © 2020 Phytochemical Society of EuropeArticle Citation - WoS: 7Citation - Scopus: 7Flavonol Glycosides From Reseda Lutea L(Elsevier Ltd., 2019) Kızıltaş, Hatice; Küçüksolak, Melis; Duman, Seda; Bedir, ErdalTwo new flavonol glycosides; kaempferol-3-O-[2-O-(beta-D-xylopyranosyl)-3-O-(beta-D-glucopyranosyl)]-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (1) and kaempferol-3-O-[2-O-((6-O-trans-p-coumaryl)-beta-D-glucopyranosyl)-3-O-(beta-D-xylopyranosyl)]-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (2) were isolated from the aerial parts of Reseda lutea L., together with five known flavonol glycosides. Structural elucidation of the compounds was based on both spectroscopic evidence and reference data comparison. The new compounds are the first tetrasaccharidic secondary metabolites isolated from Resedaceae family.Article Citation - WoS: 8Citation - Scopus: 9Ligand-Based Virtual Screening and Molecular Docking of Two Cytotoxic Compounds Isolated From Papaver Lacerum(Elsevier Ltd., 2019) Bayazeid, Omer; Bedir, Erdal; Yalçın, Funda N.This study revealed that the Papaver lacerum extract strongly inhibited HeLa cell proliferation, resulting in 13% cell viability. As a result of phytochemical studies, one known compound, Tyrosol-1-O-beta-xylopyranosyl-(1 -> 6)-O-beta-glucopyranoside) (I), and one new compound, 5-O-(6-O-alpha-rhamnopyronosyl-beta-glucopyronosyl) mevalonic acid (II), were isolated. Compounds I and II were found to possess a moderate cytotoxic effect with an IC50 of 66.4 mu M (p < 0.0001) and 54 mu M (p < 0.0001), respectively. The ligand-based virtual screening technique was used to reveal the possible molecular target of compounds I and II. The molecular target was identified as protein-tyrosine kinase Syk for compound I, and aldo-keto reductase family-1 for compound II. Molecular docking was used to assess the binding affinity of the compounds with the targets obtained from ligand-based virtual screening.Article Citation - WoS: 34Citation - Scopus: 36Biomimetic Hybrid Scaffold Consisting of Co-Electrospun Collagen and Pllcl for 3d Cell Culture(Elsevier Ltd., 2019) Türker, Esra; Yıldız, Ümit Hakan; Arslan Yıldız, AhuElectrospun collagen is commonly used as a scaffold in tissue engineering applications since it mimics the content and morphology of native extracellular matrix (ECM) well. This report describes "toxic solvent free" fabrication of electrospun hybrid scaffold consisting of Collagen (Col) and Poly(L-lactide-co-epsilon-caprolactone) (PLLCL) for three-dimensional (3D) cell culture. Biomimetic hybrid scaffold was fabricated via co-spinning approach where simultaneous electrospinning of PLLCL and Collagen was mediated by polymer sacrificing agent Polyvinylpyrrolidone (PVP). Acidified aqueous solution of PVP was used to solubilize collagen without using toxic solvents for electrospinning, and then PVP was readily removed by rinsing in water. Mechanical characterizations, protein adsorption, as well as biodegradation analysis have been conducted to investigate feasibility of biomimetic hybrid scaffold for 3D cell culture applications. Electrospun biomimetic hybrid scaffold, which has 3D-network structure with 300-450 nm fiber diameters, was found to be maximizing cell adhesion through assisting NIH 3T3 mouse fibroblast cells. 3D cell culture studies confirmed that presence of collagen in biomimetic hybrid scaffold have created a major impact on cell proliferation compared to conventional 2D systems on long-term, also cell viability increased with the increasing amount of collagen. (c) 2019 Elsevier B.V. All rights reserved.Article Citation - WoS: 16Citation - Scopus: 17Antiproliferative Activity of (r)-4 '-methylklavuzon on Hepatocellular Carcinoma Cells and Epcam(+)/Cd133(+) Cancer Stem Cells Via Sirt1 and Exportin-1 (crm1) Inhibition(Elsevier Ltd., 2019) Delman, Murat; Avcı, Sanem Tercan; Akçok, İsmail; Kanbur, Tuğçe; Erdal, Esra; Çağır, AliCytotoxic effects of (R)-4'-methylklavuzon were investigated on hepatocellular carcinoma cells (HuH-7 and HepG2) and HuH-7 EpCAM(+)/CD133(+) cancer stem cells. IC50 of (R)-4'-methylklavuzon was found as 1.25 mu M for HuH-7 parental cells while it was found as 2.50 mu M for HuH-7 EpCAM(+)/CD133(+) cancer stem cells. (R)-4'-methylklavuzon tended to show more efficient in vitro cytotoxicity with its lower IC50 values on hepatocellular carcinoma cell lines compared to its lead molecule, goniothalamin and FDA-approved drugs, sorafenib and regorafenib. Cell-based Sirtuin/HDAC enzyme activity measurements revealed that endogenous Sirtuin/HDAC enzymes were reduced by 40% compared to control. SIRT1 protein levels were upregulated indicating triggered DNA repair mechanism. p53 was overexpressed in HepG2 cells. (R)-4'methylklavuzon inhibited CRM1 protein providing increased retention of p53 and RIOK2 protein in the nucleus. HuH-7 parental and EpCAM(+)/CD133(+) cancer stem cell spheroids lost intact morphology. 3D HepG2 spheroid viabilities were decreased in a correlation with upregulation in p53 protein levels. (C) 2019 Elsevier Masson SAS. All rights reserved.Article Citation - WoS: 21Citation - Scopus: 16A Facile Method To Fabricate Propolis Enriched Biomimetic Pva Architectures by Co-Electrospinning(Elsevier Ltd., 2020) Bilginer, Rümeysa; Arslan Yıldız, AhuThis study depicts easy process of propolis by co-electrospinning without using any toxic agent for biomedical applications. To achieve this, polyvinyl alcohol was utilized as co-spinning agent to fabricate biomimetic Propolis/PVA scaffold. Here, whilst PVA was used as a supportive material to accumulate propolis in scaffold, propolis was employed to enrich biologic aspect of scaffold. This strategy overcomes challenges of propolis processing originated from solubility problems and offers easy processability of propolis in order to use in biomedical applications. Electrospun Propolis/PVA scaffolds were crosslinked with glutaraldehyde and drop-cast model was utilized as a control. Formation of porous, bead-free nanofiber architectures was confirmed through surface morphology analysis, while drop-cast model shows non-porous morphology. Wettability results confirmed both crosslinking and integration of propolis into polyvinyl alcohol scaffold moved contact angle to hydrophobic region. Presence and amount of propolis in hybrid scaffolds were validated via absorbance spectrum results. Bioactivity and biocompatibility of propolis-enriched scaffolds were analyzed through protein adsorption capacity. Obtained findings are evidence that electrospinning methodology offers easy and biosafe process of propolis. Electrospun Propolis/PVA exhibits desired properties and could be potentially utilized as scaffold for tissue engineering or as a wound dressing graft in biomedical field. © 2020 Elsevier B.V.Article Citation - WoS: 14Citation - Scopus: 15Biotransformation of Ruscogenins by Cunninghamella Blakesleeana Nrrl 1369 and Neoruscogenin by Endophytic Fungus Neosartorya Hiratsukae(Elsevier Ltd., 2018) Özçınar, Özge; Tağ, Özgür; Yusufoğlu, Hasan; Kıvçak, Bijen; Bedir, ErdalBiotransformation of steroidal ruscogenins (neoruscogenin and ruscogenin) was carried out with Cunninghamella blakesleeana NRRL 1369 and endophytic fungus Neosartorya hiratsukae yielding mainly P450 monooxygenase products together with a glycosylated compound. Fermentation of ruscogenins (75:25, neoruscogenin-ruscogenin mixture) with C. blakesleeana yielded 8 previously undescribed hydroxylated compounds. Furthermore, microbial transformation of neoruscogenin by endophytic fungus N. hiratsukae afforded three previously undescribed neoruscogenin derivatives. While hydroxylation at C-7, C-12, C-14, C-21 with further oxidation at C-1 and C-7 were observed with C. blakesleeana, N. hiratsukae biotransformation provided C-7 and C-12 hydroxylated compounds along with C-12 oxidized and C-1(O) glycosylated derivatives. The structures of the metabolites were elucidated by 1-D (1H, 13C and DEPT135) and 2-D NMR (COSY, HMBC, HMQC, NOESY, ROESY) as well as HR-MS analyses.