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    Active surface modification of thermoplastic polyurethane-oleic acid nanocomposite fibers through alkali hydrolysis
    (John Wiley and Sons Inc, 2025) Karahaliloğlu, Zeynep; Hazer, Baki
    Alkali hydrolysis is a simple, low-cost, and prominent surface modification method for developing more desirable scaffolds. In the presented study, two distinct concentrations (1 and 3 M) were predetermined for the hydrolysis treatments, and thermoplastic polyurethane (TPU) nanocomposite fibers with varying concentrations of oleic acid (OLE) were exposed. According to the scanning electron microscopy (SEM) images, when naked TPU or nanocomposite fibers showed any morphological changes, the interfacial bonding points of TPU-OLE nanocomposite fibers enhanced in the higher concentrations of hydrolysis solution (1 and 3 M). The average fiber diameter in pure TPU is 0.59 ± 0.04 μm, while after doping with the highest concentration of OLE, the fiber diameter decreased to 0.48 ± 0.03 μm. Additionally, at the highest NaOH and OLE concentrations, the diameter decreased from 0.85 ± 0.02 μm in 3 M/TPU to 0.61 ± 0.04 μm in 3 M/TPU-OLE3. Additionally, the surface hydrophilicity of TPU-OLE fibers was noticeably improved through alkali hydrolysis, compared to the naked TPU approximately by 70%. Furthermore, the surface characterization of fibers revealed that the surface roughness values showed a significant change with increasing alkali concentration, but were not affected by the OLE concentration. All these findings indicate that TPU, whose surface wettability, roughness, and antibacterial response are modified by mercerization and OLE addition, can be safely and successfully used in tissue engineering applications. Highlights: Polyurethane, oleic acid, and NaOH treatment were combined for tissue engineering applications. TPU/OLE nanofiber membranes were prepared by electrospinning. The surface of composite fibrillar membranes was modified alkali hydrolysis. The fiber diameter decreased after NaOH hydrolysis. Alkali hydrolysis improved the surface wettability and antibacterial response.
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    Antisense oligonucleotide delivery to cancer cell lines for the treatment of different cancer types
    (Taylor & Francis Ltd, 2016) Kılıçay, Ebru; Erdal, Ebru; Hazer, Baki; Türk, Mustafa; Denkbaş, Emir Baki
    Amphiphilic poly(3-hydroxylalkanoate) (PHA) copolymers find interesting applications in drug delivery. The aim of this study was to prepare nucleic acid adsorbed on (PHB-b-PEG-NH2) nanoparticle platform for gene delivery. For this purpose, PHB-b-PEG-NH2 block copolymers were synthesized via transesterification reactions. The copolymers obtained were characterized by Proton Nuclear Magnetic Resonance (H-1-NMR), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) techniques. The cytotoxic, apoptotic and necrotic effects of these nanoparticles in the MDA 231 human breast cancer cell, the A549 human lung cancer cell and the L929 fibroblast cell lines were also investigated.
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    Biocompatible PVC Derivatives with Some Natural Substances for Potential Active Food Packaging Materials
    (ACS Publications, 2023) Hazer, Baki; Karahaliloğlu, Zeynep
    Monoethyl fumarate (mef), bovine serum albumin (bsa), abietic acid (ab), morphine (mrp), aspirin (asp), indole (ind), and lysozyme (lysz) functionalized poly vinyl chloride (PVC) samples were synthesized for possible application of the active food packaging materials. Antioxidant properties of the new PVC-derivatives were determined by inhibition of the autoxidation of linseed oil via following its oligomerization. For this purpose, linseed oil was laid on the obtained PVC derivatives and exposed to air oxygen. Oligomerization of autoxidized linseed oil was measured by the increase in viscosity using an Ubbelohde viscometer. Because of the inhibition of autoxidation, oligomerization of the linseed oil lasted longer. The autoxidation time of linseed oil was delayed on the PVC-natural compound derivatives. Considering the delaying time, the antioxidant effect on the linseed oil was in the following order: PVC-abietic acid (29 days) > PVC-bovine serum albumin (24 days) > PVC-indole (21 days) > PVC-lysozyme (20 days) > PVC-mono ethyl fumarate (16 days); PVC-aspirin (16 days); Petri dish (16 days) > PVC-morphine (15 days) > PVC-control (14 days). The antibacterial activities of the novel PVC derivatives were assessed against Escherichia coli and Staphylococcus aureus bacteria. PVC-aspirin and -indole membranes showed significant antibacterial effect against E. coli and S. aureus. Also, according to flow cytometer results, a live cell percent above 90% was obtained for PVC derivative membranes.
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    Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded with curcumin for breast cancer therapy
    (Taylor & Francis, 2016) Kılıçay, Ebru; Karahaliloğlu, Zeynep; Hazer, Baki; Tekin, İshak Özel; Denkbaş, Emir Baki
    The aim of this study was to evaluate therapeutic potential of curcumin-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer treatment. The size and zeta potential of prepared NPs were about 228 +/- 5nm and -23.3mV, respectively. The entrapment efficiencies of polymer/drug weight ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and ConA-5CUR-NPs were found to be approximate to 68, 55, 45, 70, 60 and 51%, respectively. Optimized NPs formulations in the freeze-dried form were assessed with their short-term stability for 30 days of storage at 4 degrees C and 25 degrees C. Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by double staining and flow cytometry results. The anticancer activity of ConA-CUR-NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the results revealed that the ConA-CUR-NPs had better tumor cells decline activity.
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    Curcumin- and quercetin-functionalized polypropylene membranes as active food packaging material
    (Wiley, 2024) Karahaliloğlu, Zeynep; Hazer, Baki
    A wide range of active agents, synthetic and natural agents such as essential oils, chitosan and polyphneols consisting of curcumin, gallic acid, anthocyanins, and catechins have been used in order to develop antimicrobial packaging systems, and among them, natural polyphenolic compounds, specially curcumin (Cur) has great potential due to effective biological activities in developing food packaging material. Quercetin (Quer) is also the mostly studied flavonol as a color-changing indicator in the food industry and has been already developed as a realistic alternative for smart and active food packaging. The reason for choosing these two polyphenolic compounds is that they simultaneously possess many beneficial properties such as antioxidant, antibacterial, antiviral, antitumoral, and anti-inflammatory effects. Additionally, the main objective of the study is to combine polypropylene (PP), which is the most preferred and cost-effective polymer in the packaging industry, with these active ingredients, rather than using more expensive polymer types. In this context, PP-Quer or PP-Cur membranes, which are new experiences based on these literatures were chemically characterized by Fourier transform infrared spectroscopy, and the surface morphology of these composite membranes was characterized by scanning electron microscopy. The antibacterial response against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria species was investigated. Furthermore, the reactive oxygen species generation and anticancer activity of these composite membranes using human colorectal adenocarcinoma (HT-29) were observed. We proposed that PP-Quer or PP-Cur composite membranes can be a potential candidate as active packaging material in the food industry.
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    Enhanced antitumor activity of epigallocatechin gallate-conjugated dual-drug-loaded polystyrene-polysoyaoil-diethanol amine nanoparticles for breast cancer therapy
    (Sage Publications Ltd, 2018) Karahaliloğlu, Zeynep; Kılıçay, Ebru; Alpaslan, Pınar; Hazer, Baki; Denkbaş, Emir Baki
    The development of novel combination anticancer drug delivery systems is an important step to improve the effectiveness of anticancer treatment in metastatic breast cancer and to overcome increased toxicity of the currently used combination treatments. The aim of this study was to assess efficient targeting, therapeutic efficacy, and bioavailability of a combination of drugs (curcumin and -tocopheryl succinate) loaded polystyrene-polysoyaoil-diethanol amine nanoparticles. Polystyrene-polysoyaoil-diethanol amine nanoparticles encapsulating two drugs, individually or in combination, were prepared by double-emulsion solvent evaporation method, resulting in particle size smaller than 250nm with a surface negative charge between -30 and -40mV. Entrapment efficiency of curcumin and -tocopheryl succinate in the epigallocatechin gallate-conjugated dual-drug-loaded nanoparticles was found to be 68% and 80%, respectively. The release kinetics of curcumin and -tocopheryl succinate from the nanoparticles exhibited a gradual and continuous profile followed by an initial burst behavior with a release over 20days in vitro. Next, we have investigated the anticancer activity of nanoparticles encapsulating both the drugs and individually drug in human breast cancer cells (MDA-MB-231) using double-staining-based cell death analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assessment of cytotoxicity and flow cytometer. In vitro cytotoxicity studies revealed that epigallocatechin gallate--tocopheryl succinate/curcumin-polystyrene-polysoyaoil-diethanol amine nanoparticles are more potent than the corresponding -tocopheryl succinate/curcumin-polystyrene-polysoyaoil-diethanol amine nanoparticles and their single-drug-loaded forms and show a synergistic and breast tumor targeting function. Thus, here, we propose epigallocatechin gallate-conjugated curcumin and -tocopheryl succinate-loaded polystyrene-polysoyaoil-diethanol amine nanoparticles which effectively inhibit tumor growth and reduce toxicity compared to single-drug chemotherapy.
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    Herceptin-conjugated magnetic polystyrene-Agsbox nanoparticles as a theranostic agent for breast cancer
    (SAGE Publications Ltd, 2022) Karahaliloğlu, Zeynep; Kılıçay, Ebru; Hazer, Baki
    Breast cancer is a malignant tumor, which has derived from cells of the breast. Further, a relatively rapid metastasis, and resistance development against all the conventional drug combinations are major clinical issues in breast cancer patients as well as limitations like toxicity, genetic mutation, and metastasis make difficult the use of conventional therapy methods such as chemotherapy, radiotherapy, and local surgery. Therefore, considering the urgent needs, and high death rate in breast cancer cases, the development of new diagnosis and treatment regimens which diagnosed at the early stage and protected normal tissues required for clinical applications. Recently, the combination of tumor diagnosis and treatment within a single platform is a novel perspective, and magnetic nanoparticles are potential candidate owing to their low toxic effect, biocompatibility, biological degradability, superior magnetic properties, and targeting ability to overcome the problems of conventional diagnosis and therapy techniques. Considering these restrictions and requirements, the goal of this research was to investigate the potential of an innovative theranostic agent, which is soybean oil-based polystyrene (PS)-g-soybean oil graft copolymer containing AgNPs (PS-Agsbox) for treatment and MRI-based diagnosis of cancer. Herein, we designed targeted magnetic PS-Agsbox nanoparticles carrying thymoquinone (TQ) that is known for its anticancer potential against breast cancer, and herceptin (HER), which is to bind to the HER2 receptor protein on the surface of HER2-positive tumor cells, and acts by blocking the effects of it. We have successfully demonstrated selective binding, effective uptake of HER-conjugated magnetic PS-Agsbox nanoparticles into MDA-MB-231 (human breast carcinoma cells, a HER2-underexpressing cell line) and SKBR-3 (human breast cancer cells, a HER2-overexpressing breast cancer cell line) cell lines while no effect against L929 (mouse fibroblast cell line). Moreover, the magnetic resonance (MRI) properties of HER-conjugated magnetic PS-Agsbox nanoparticles were also confirmed.
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    Impregnation of polyethylene terephthalate (PET) grafts with BMP-2 loaded functional nanoparticles for reconstruction of anterior cruciate ligament
    (Taylor & Francis, 2023) Karahaliloğlu, Zeynep; Ercan, Batur; Hazer, Baki
    Current artificial ligaments based on polyethylene terephthalate (PET) are associated with some disadvantages due to their hydrophobicity and low biocompatibility. In this study, we aimed to modify the surface of PET using polyethylene glycol (PEG)-terminated polystyrene (PS)-linoleic nanoparticles (PLinaS-g-PEG-NPs). We accomplished that BMP-2 in two different concentrations encapsulated in nanoparticles with an efficiency of 99.71 ± 1.5 and 99.95 ± 2.8%. While the dynamic contact angle of plain PET surface reduced from 116° to 115° after a measurement periods of 10 s, that of PLinaS-g-PEG-NPs modified PET from 80° to 17.5° within 0.35 s. According to in vitro BMP2 release study, BMP-2 was released 13.12 ± 1.76% and 45.47 ± 1.78% from 0.05 and 0.1BMP2-PLinaS-g-PEG-NPs modified PET at the end of 20 days, respectively. Findings from this study revealed that BMP2-PLinaS-g-PEG-NPs has a great potential to improve the artificial PET ligaments, and could be effectively applied for ACL reconstruction.
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    In vitro evaluation of antisense oligonucleotide functionalized core-shell nanoparticles loaded with -tocopherol succinate
    (Taylor & Francis, 2017) Kılıçay, Ebru; Karahalıloğlu, Zeynep; Alpaslan, Pınar; Hazer, Baki; Denkbaş, Emir Baki
    Antisense oligonucleotide (ASO)-conjugated--tocopherol succinate (TCS)-loaded-poly(lactic acid)-g-poly(ethylene glycol) nanoparticles (ASO-TCS-PLA-PEG NPs), with the ratio of polymer/TCS of 10:2.5, 10:5, 10:7 (w/w) were prepared for targeting cancer therapy. The amphiphilic PLA, amino terminated PEG graft copolymers were synthesized by ring opening polymerization reaction. Nanoparticles were produced by using double emulsion (w/o/w) solvent evaporation method. ASO-TCS-PLA-PEG NPs demonstrated satisfactory encapsulation and loading efficiency and size distribution. The short-term stability studies were carried out at 4 and 25 degrees C for 30days to assess their mean particle size, polydispersity index and zeta potential. The cellular uptake and extended cytoplasmic retention of the NPs in A549 human lung carcinoma and L929 mouse fibroblast cells were examined by fluorescence and confocal microscopy. In human lung cancer cells, ASO-TCS-PLA-PEG NPs exhibited better cellular internalization, cytotoxicity and apoptotic and necrotic effects compared to healthy cell line, L929. These findings showed that ASO-modified nanoparticles could serve as a promising nanocarrier for targeted tumor cells.
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    PLinaS-g-PEG coated magnetic nanoparticles as a contrast agent for hepatocellular carcinoma diagnosis
    (Taylor and Francis Inc., 2020) Karahalilo?lu, Zeynep; Kılıçay, Ebru; Hazer, Baki
    Among many different types of fabricated nanoparticles, magnetic iron oxide nanoparticles (MNPs) have unique physical and chemical properties and have been widely used due to theirs enhanced permeability and retention effect for biomedical applications. The incorporated theranostic MNPs into biopolymer coatings are currently particular interest to investigators in the fields of nanobiomedicine because of efficiently delivering of various drugs, genes and providing imaging properties. Hepatocellular carcinoma (HCC) is the most prevalent reason of cancer-related deaths, makes it one of the worst malignant tumors in the world. Because, there is a lack of effective treatment methods for HCC, aforementioned magnetic carrier technology with recent innovations could be a promising tool in HCC diagnosis and treatment. Therefore, this study proposes a novel fatty-acid-based polymeric magnetic nanoprobe for diagnosis of hepatocellular tumors using polyethylene glycol (PEG)-terminated polystyrene (PS)-linoleic copolymer coated magnetic iron oxide nanoparticles. MNPs were synthesized by a co-precipitation method and were subsequently coated with a copolymer containing PEG group as termini. Fifty-nanometer-sized MNPs were incorporated into the core of PLinaS-g-PEG nanoparticles. The morphology and size distribution of the bare and magnetic PLinaS-g-PEG were determined by transmission electron microscopy (TEM), and dynamic light scattering (DLS), respectively. MTT and flow cytometry assays showed that PLinaS-g-PEG MNPs demonstrated ultrasentive apoptotic behavior against cancerous cell line, i.e. HepG2 in the culture plate when the fatty acid-containing polymer coated MNPs showed no adverse effect on L929 cell growth. The localization, and accumulation in hepatocytes of PLinaS-g-PEG MNPs without specific targeting ligand was confirmed by fluorescence and confocal microscopy. Therefore, PLinaS-g-PEG MNPs may be potentially used as a unique candidate for diagnosis of hepatocellular carcinomas.
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    Poly(vinyl chloride) Derived Food Packaging Applications with Antioxidative and Anticancer Properties
    (American Chemical Society, 2023) Hazer, Baki; Karahaliloğlu, Zeynep; Ashby, Richard D.
    Novel poly(vinyl chloride) (PVC) polymer derivatives based on the natural antioxidants vanillic acid, cinnamic acid, coumaric acid, caffeic acid, and naringin were prepared and characterized for their chemical structures, molecular weights, thermal and mechanical properties, and antioxidant characteristics toward linseed oil. Oxidation delay times (induction periods) were prolonged from 1 to 6 days beyond the pristine PVC, with the naringin-based derivative being the most effective. Biological activities of the PVC derivatives were determined and showed the substituted PVC polymers effectively inhibited the formation of reactive oxygen species (ROS) in the MCF-7 cell line according to the following sequence: cinnamic acid ? caffeic acid ? vanillic acid = naringin ? coumaric acid, with only a minimal effect on healthy L929 cells. These results indicate that the derivatives produced in this study have potential applications as active packaging materials for food and as antibacterial/anticancer biomaterials in areas such as tissue engineering.
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    Potent bioactive bone cements impregnated with polystyrene-g-soybean oil-AgNPs for advanced bone tissue applications
    (Taylor & Francis, 2020) İlhan, Elif; Karahaliloğlu, Zeynep; Kılıçay, Ebru; Hazer, Baki; Denkbaş, Emir Baki
    Postoperative infection in orthopaedic and trauma surgery is one of the most feared complications. Recently, the high prevalence of multidrug-resistant bacteria has made the antibiotic treatment ineffective; thus novel non-antibiotic alternative approaches to this problem are urgently needed. Based on these expectations, in this work, in order to enhance the cytocompatibility and antibacterial performances of poly (methyl methacrylate (PMMA) and beta-tricalcium phosphate (?TCP) bone cements were impregnated with polystyrene (PS)-g-soybean oil graft copolymer containing AgNPs (PS-Agsbox), and we assessed the antimicrobial activity of the fabricated bone cements against Staphylococcus aureus and Escherichia coli. Nanoparticles at concentration of 1.25% (5 ?-TCP) w/w in ?-TCP bone cements were able to inhibit pathogens growth, while a concentration of 3.75% (15PMMA) was needed for PMMA bone cement. Therefore, the impregnated bone cements with PS-AgsboxNPs may be further explored as an alternative antimicrobial therapy for the treatment of infected bone defects.
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    Prevention of urinary infection through the incorporation of silver-ricinoleic acid-polystyrene nanoparticles on the catheter surface
    (Karatekin University, 2021) Koç, Hazal; Kılıçay, Ebru; Karahaliloğlu, Zeynep; Hazer, Baki; Denkbaş, Emir B.
    Nosocominal infections associated with biofilm formation on urinary catheters cause serious complications. The aim of this study was to investigate the feasibility of the polyurethane (PU) catheter modified with tetracycline hydrochloride (TCH) attached Ag nanoparticles embedded PolyRicinoleic acid-Polystyrene Nanoparticles (PU-TCH-AgNPs-PRici-PS NPs) and the influence on antimicrobial and antibiofilm activity of urinary catheters infected by Escherichia coli and Staphylococcus aureus. For this purpose, AgNPs embedded PRici graft PS graft copolymers (AgNPs-PRici-g-PS) were synthesized via free radical polymerization and characterized by FTIR, HNMR and DSC. AgNPs-PRici-PS NPs were prepared and optimized by the different parameters and the optimized size of nanoparticle was found as about 150 +/- 1 nm. The characterization of the nanoparticles and the morphological evaluation were carried out by FTIR and SEM. Short term stability of nanoparticles was realised at 4 degrees C for 30 days. In vitro release profiles of TCH and Ag NPs were also investigated. The formation of biofilm on PU modified TCH-Ag NPs-PRici-PS NPs, was evaluated and the biocompatibility test of the nanoparticles was realized via the mouse fibroblast (L929) and mouse urinary bladder cells (G/G An1). This is the first time that TCH-AgNPs-PRici-PS NPs used in the modification of PU catheter demonstrated high antimicrobial and antibiofilm activities against the urinary tract infection.
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    The preparation of chitosan membrane improved with nanoparticles based on unsaturated fatty acid for using in cancer-related infections
    (SAGE Publications Ltd, 2020) Kızaloğlu, Abdullah; Kılıçay, Ebru; Karahalilo?lu, Zeynep; Hazer, Baki; Denkbaş, Emir Baki
    This study includes the design of a chitosan membrane decorated with unsaturated fatty acid–based carrier system for cancer treatment and antibacterial application. For this, polystyrene-graft-polyoleic acid-graft-polyethylene glycol was prepared by free radical polymerization and characterized. Nanoparticles and caffeic acid–loaded nanoparticles were prepared by solvent evaporation technique and optimized. The short-term stability of nanoparticles was investigated at 4°C. Drug encapsulation and loading efficiency were evaluated. The chitosan membrane and caffeic acid–loaded nanoparticles embedded into chitosan membrane were fabricated. The caffeic acid loaded nanoparticles embedded into chitosan membrane showed controlled release. The mechanical properties of all samples were investigated. The caffeic acid–loaded nanoparticles embedded into chitosan membranes indicated excellent antibacterial properties against the Escherichia coli and Staphylococcus aureus. The anticancer activity of all the samples was evaluated against SaOS-2 human primary osteogenic sarcoma and MC3T3-E1 pre-osteoblast cell lines by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, the flow cytometry and double staining methods. As a result, the designed carrier system showed great potential to cancer-associated infections treatment in bone cancer cases.
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    Thermoplastic Polyurethane-Oleic Acid (TPU-OLE) Membranes for Guided Bone Regeneration
    (John Wiley and Sons Inc, 2025) Karahaliloğlu, Zeynep; Hazer, Baki
    Guided bone regeneration (GBR) is a regenerative surgical procedure in dentistry and orthopedics. The aim of this study is to fabricate a novel nano-textured, hydrophilic thermoplastic polyurethane (TPU)-based barrier membrane containing unsaturated fatty acid, oleic acid (OLE) to assist GBR. First, TPU copolymer containing OLE in different ratios was synthesized, and GBR membranes were fabricated by the solvent casting method, and then, the surface properties were improved by alkali treatment. Thus, a TPU-OLE structure was obtained with improved surface wettability, the ability to prevent bacterial adhesion, and the capability to promote cell adhesion. The contact angle reduced from 73.3° ± 1° to 30.7° ± 0.3° at TPU-OLE3, while at TPU it decreased from 121.2° ± 2.5° to 63.6° ± 0.8° after treatment with 3 M sodium hydroxide (NaOH) solution. Furthermore, plate counting assays showed that TPU-OLE membranes displayed excellent bacterial inhibition (against Escherichia coli and Staphylococcus aureus); the control group showed 6 × 107 CFU/mL of E. coli bacterial colonies, while on the plates interacting with TPU-OLE1, TPU-OLE2, and TPU-OLE3 membranes, colonies of 12 × 105, 12 × 105, and 24 × 105 CFU/mL were observed, respectively. The bacterial count on TPU-OLE1, TPU-OLE2, and TPU-OLE3 membranes decreased by 109, 164, and 12 × 105 CFU/mL at 24 h, while the control group and TPU membranes showed 1300 × 105 and 600 × 105 CFU/mL, respectively. The obtained results indicated that either alkali treatment or OLE-modified TPU produced a more hydrophilic and promotive surface for cell attachment. Therefore, we anticipate that alkali-treated TPU-OLE membranes have a great potential in GBR in future applications.

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