Person: YILMAZ, BETÜL
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YILMAZ
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BETÜL
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Publication Metadata only Design and fabrication of electrospun polycaprolactone/chitosan scaffolds for ligament regeneration(PERGAMON-ELSEVIER SCIENCE LTD, 2021) İNAN, AHMET TALAT; Saatcioglu, Elif; Ulag, Songul; Sahin, Ali; Yilmaz, Betul Karademir; Ekren, Nazmi; Inan, Ahmet Talat; Palaci, Yuksel; Ustundag, Cem Bulent; Gunduz, OguzhanTendon and ligament impairments are among the most familiar injuries of the knee with acute or chronic pain conditions. The defects of anterior cruciate ligament (ACL) stay a known clinical problem. In the present study, the electrospinning method was used to fabricate 10wt.%PCL/(1, 3, 5)wt.%Chitosan (CS) appropriate and biocompatible scaffolds with a similar connective ligament geometry and structure. 10wt.%PCL/3wt.%CS demonstrated higher tensile strength value (0.58854 MPa) than other scaffolds in the tensile test. Moreover, 10wt.%PCL/3wt.%CS scaffolds had high mesenchymal stem cells (MSCs) viability value for all incubation periods. Swelling and degradation behaviours of the ligament-like scaffolds were examined in vitro for 15 days. Results reported that the highest swelling ratio was observed with CS addition for 10wt.%PCL/5wt.%CS scaffolds which value nearly reached to the 270% ratio. Scanning electron microscope proved the geometry of the scaffolds, which were suitable for ligament-like tissue. Attachment of MSCs on the scaffolds proved the network-like structure of the cells on the scaffolds.Publication Open Access Propolis-Based Nanofiber Patches to Repair Corneal Microbial Keratitis(MDPI, 2021-04-28) ŞAHİN, ALİ; Ulag, Songul; Ilhan, Elif; Demirhan, Ramazan; Sahin, Ali; Yilmaz, Betul Karademir; Aksu, Burak; Sengor, Mustafa; Ficai, Denisa; Titu, Aurel Mihail; Ficai, Anton; Gunduz, OguzhanIn this research, polyvinyl-alcohol (PVA)/gelatin (GEL)/propolis (Ps) biocompatible nanofiber patches were fabricated via electrospinning technique. The controlled release of Propolis, surface wettability behaviors, antimicrobial activities against the S. aureus and P. aeruginosa, and biocompatibility properties with the mesenchymal stem cells (MSCs) were investigated in detail. By adding 0.5, 1, and 3 wt.% GEL into the 13 wt.% PVA, the morphological and mechanical results suggested that 13 wt.% PVA/0.5 wt.% GEL patch can be an ideal matrix for 3 and 5 wt.% propolis addition. Morphological results revealed that the diameters of the electrospun nanofiber patches were increased with GEL (from 290 nm to 400 nm) and Ps addition and crosslinking process cause the formation of thicker nanofibers. The tensile strength and elongation at break enhancement were also determined for 13 wt.% PVA/0.5 wt.% GEL/3 wt.% Ps patch. Propolis was released quickly in the first hour and arrived at a plateau. Cell culture and contact angle results confirmed that the 3 wt.% addition of propolis reinforced mesenchymal stem cell proliferation and wettability properties of the patches. The antimicrobial activity demonstrated that propolis loaded patches had antibacterial activity against the S. aureus, but for P. aeruginosa, more studies should be performed.Publication Metadata only Glioblastoma cell adhesion properties through bacterial cellulose nanocrystals in polycaprolactone/gelatin electrospun nanofibers(ELSEVIER SCI LTD, 2020) YILMAZ, BETÜL; Unal, Semra; Arslan, Sema; Yilmaz, Betul Karademir; Kazan, Dilek; Oktar, Faik Nuzhet; Gunduz, OguzhanGlioblastoma (GBM), the most common and extremely lethal type of brain tumor, is resistant to treatment and shows high recurrence rates. In the last decades, it is indicated that standard two-dimensional (2D) cell culture is inadequate to improve new therapeutic strategies and drug development. Hence, well-mimicked three-dimensional (3D) tumor platforms are needed to bridge the gap between in vitro and in vivo cancer models. In this study, bacterial cellulose nano-crystal (BCNC) containing polycaprolactone (PCL) /gelatin (Gel) nanofibrous composite scaffolds were successfully fabricated by electrospinning for mimicking the extracellular matrix of GBM tumor. The fiber diameters in the nanofibrous matrix were increased with an increased concentration of BCNC. Moreover, fiber morphology changed from the smooth formation to the beaded formation by increasing the concentration of the BCNC suspension. In-vitro biocompatibilities of nanofibrous scaffolds were tested with U251 MG glioblastoma cells and improved cell adhesion and proliferation was compared with PCL/Gel. PCL/Gel/BCNC were found suitable for enhancing axon growth and elongation supporting communication between tumor cells and the microenvironment, triggering the process of tumor recurrence. Based on these results, PCL/Gel/BCNC composite scaffolds are a good candidate for biomimetic GBM tumor platform.Publication Open Access Polycaprolactone/Gelatin/Hyaluronic Acid Electrospun Scaffolds to Mimic Glioblastoma Extracellular Matrix(MDPI, 2020-06-11) YILMAZ, BETÜL; Unal, Semra; Arslan, Sema; Yilmaz, Betul Karademir; Oktar, Faik Nuzhet; Ficai, Denisa; Ficai, Anton; Gunduz, OguzhanGlioblastoma (GBM), one of the most malignant types of human brain tumor, is resistant to conventional treatments and is associated with poor survival. Since the 3D extracellular matrix (ECM) of GBM microenvironment plays a significant role on the tumor behavior, the engineering of the ECM will help us to get more information on the tumor behavior and to define novel therapeutic strategies. In this study, polycaprolactone (PCL)/gelatin(Gel)/hyaluronic acid(HA) composite scaffolds with aligned and randomly oriented nanofibers were successfully fabricated by electrospinning for mimicking the extracellular matrix of GBM tumor. We investigated the effect of nanotopography and components of fibers on the mechanical, morphological, and hydrophilic properties of electrospun nanofiber as well as their biocompatibility properties. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) have been used to investigate possible interactions between components. The mean fiber diameter in the nanofiber matrix was increased with the presence of HA at low collector rotation speed. Moreover, the rotational velocity of the collector affected the fiber diameters as well as their homogenous distribution. Water contact angle measurements confirmed that hyaluronic acid-incorporated aligned nanofibers were more hydrophilic than that of random nanofibers. In addition, PCL/Gel/HA nanofibrous scaffold (7.9 MPa) exhibited a significant decrease in tensile strength compared to PCL/Gel nanofibrous mat (19.2 MPa). In-vitro biocompatibilities of nanofiber scaffolds were tested with glioblastoma cells (U251), and the PCL/Gel/HA scaffolds with random nanofiber showed improved cell adhesion and proliferation. On the other hand, PCL/Gel/HA scaffolds with aligned nanofiber were found suitable for enhancing axon growth and elongation supporting intracellular communication. Based on these results, PCL/Gel/HA composite scaffolds are excellent candidates as a biomimetic matrix for GBM and the study of the tumor.Publication Metadata only Fabrication of tissue-engineered tympanic membrane patches using 3D-Printing technology(ELSEVIER, 2021) ŞAHİN, ALİ; Ilhan, Elif; Ulag, Songul; Sahin, Ali; Yilmaz, Betul Karademir; Ekren, Nazmi; Kilic, Osman; Sengor, Mustafa; Kalaskar, Deepak M.; Oktar, Faik Nuzhet; Gunduz, OguzhanIn recent years, scaffolds produced in 3D printing technology have become more widespread tool due to providing more advantages than traditional methods in tissue engineering applications. In this research, it was aimed to produce patches for the treatment of tympanic membrane perforations which caused significant hearing loss by using 3D printing method. Polylactic acid(PLA) scaffolds with Chitosan(CS) and Sodium Alginate(SA) added in various ratios were prepared for artificial eardrum patches. Different amounts of chitosan and sodium alginate added to PLA increased the biocompatibility of the produced scaffolds. The created patches were designed by mimicking the thickness of the natural tympanic membrane thanks to the precision provided by the 3D printed method. The produced scaffolds were analyzed separately for chemical, morphological, mechanical and biocompatibility properties. Scanning electron microscope (SEM), Fourier-transform infrared (FT-IR) spectroscopy was performed to observe the surface morphology and chemical structure of the scaffolds. Mechanical, thermal and physical properties, swelling and degradation behaviors were examined to fully analyze whole characteristic features of the samples. Cell culture study was also performed to demonstrate the biocompatibility properties of the fabricated scaffolds with human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). 15 wt % PLA was selected as the control group and among all concentrations of CS and SA, groups containing 3 wt% CS and 3 wt% SA showed significantly superior and favorable features in printing quality. The research continued with these two scaffolds (3 wt% CS, and 3 wt% SA), which showed improved print quality when added to PLA. Overall, these results show that PLA/CS and PLA/SA 3D printed artificial patches have the potential to tissue engineering solutions to repair tympanic membrane perforation for people with hearing loss.Publication Metadata only Indocyanine green based fluorescent polymeric nanoprobes for in vitro imaging(WILEY, 2020) YILMAZ, BETÜL; Ege, Zeynep R.; Akan, Aydin; Oktar, Faik N.; Lin, Chi C.; Kuruca, Durdane S.; Karademir, Betul; Sahin, Yesim M.; Erdemir, Gokce; Gunduz, OguzhanIndocyanine green (ICG) provides an advantage in the imaging of deep tumors as it can reach deeper location without being absorbed in the upper layers of biological tissues in the wavelengths, which named therapeutic window in the tissue engineering. Unfortunately, rapid elimination and short-term stability in aqueous media limited its use as a fluorescence probe for the early detection of cancerous tissue. In this study, stabilization of ICG was performed by encapsulating ICG molecules into the biodegradable polymer composited with poly(l-lactic acid) and poly(epsilon-caprolactone) via a simple one-step multiaxial electrospinning method. Different types of coaxial and triaxial structure groups were performed and compared with single polymer only groups. Confocal microscopy was used to image the encapsulated ICG (1 mg/mL) within electrospun nanofibers and in vitro ICG uptake by MIA PaCa-2 pancreatic cancer cells. Stability of encapsulated ICG is demonstrated by the in vitro sustainable release profile in PBS (pH = 4 and 7) up to 21 days. These results suggest the potential of the ability of internalization and accommodation of ICG into the pancreatic cell cytoplasm from in vitro implanted ICG-encapsulated multiaxial nanofiber mats. ICG-encapsulated multilayer nanofibers may be promising for the local sustained delivery system to eliminate loss of dosage caused by direct injection of ICG-loaded nanoparticles in systemic administration.Publication Metadata only Effect of electric stimulus on human adipose-derived mesenchymal stem cells cultured in 3D-printed scaffolds(WILEY, 2021) ŞAHİN, ALİ; Bedir, Tuba; Ulag, Songul; Aydogan, Kivanc; Sahin, Ali; Yilmaz, Betul Karademir; Guvenc, Yahya; Bozlar, Michael; Ustundag, Cem Bulent; Gunduz, OguzhanElectrical stimulation has shown great potential for nerve regeneration processes. This makes it attractive to use electrically active materials in the neural scaffold. In this paper, bismuth ferrite (BFO) nanoparticles were synthesized via co-precipitation method and incorporated to 10 wt% polylactic acid (PLA) in chloroform to obtain 3D-printed PLA/BFO biocomposites. The crystallinity of BFO nanoparticles was confirmed by XRD, and we studied its chemical structure with FTIR, as well as the mechanical properties of the 3D-printed composites. in vitro studies show that 3D-printed scaffolds have no cytotoxicity and support the proliferation of human adipose-derived mesenchymal stem cells (hADMSCs). Furthermore, 3D scaffolds embedded with BFO shows the highest cell viability relative to pristine PLA and BFO-lined PLA scaffolds. A 48 hours electrical stimulation on the hADMSC cultured inside the 3D-printed BFO-lined PLA scaffolds indicates that stimulated cells are aligned toward the BFO line. These results could indicate the potential of BFO for directing cells toward damaged tissues.Publication Open Access 3D printed artificial cornea for corneal stromal transplantation(PERGAMON-ELSEVIER SCIENCE LTD, 2020-06) ŞAHİN, ALİ; Ulag, Songul; Ilhan, Elif; Sahin, Ali; Yilmaz, Betul Karademir; Kalaskar, Deepak M.; Ekren, Nazmi; Kilic, Osman; Oktar, Faik Nuzhet; Gunduz, OguzhanThe aim of this study is to understand the optical, biocompatible, and mechanical properties of chitosan (CS) and polyvinyl-alcohol (PVA) based corneal stroma constructs using 3D printing process. Corneal stroma is tested for biocompatibility with human adipose tissue-derived mesenchymal stem cells (hASCs). Physico-chemical and chemical characterization of the construct was performed using scanning electron microscopy (SEM), fourier transforms infrared spectroscopy (FTIR). Optical transmittance was analyzed using UV-Spectrophotometer. Results showed fabricated constructs have required shape and size. SEM images showed construct has thickness of 400 mu m. The FTIR spectra demonstrated the presence of various predicted peaks. The swelling and degradation studies of 13%(wt)PVA and 13%(wt)PVA/(1, 3, 5)%(wt)CS showed to have high swelling ratios of 7 days and degradation times of 30 days, respectively. The light transmittance values of the fabricated cornea constructs decreased with CS addition slightly. Tensile strength values decreased with increasing CS ratio, but we found to support intraocular pressure (IOP) which ranges from 12 to 22 mm-Hg. Preliminary biostability studies showed that composite constructs were compatible with hASCs even after 30 days' of degradation, showing potential for these cells to be differentiated to stroma layer in future. This study has implications for the rapid and custom fabrication of various cornea constructs for clinical applications.Publication Metadata only Production and characterization of bacterial cellulose scaffold and its modification with hyaluronic acid and gelatin for glioblastoma cell culture(SPRINGER, 2021) YILMAZ, BETÜL; Unal, Semra; Arslan, Sema; Yilmaz, Betul Karademir; Oktar, Faik Nuzhet; Sengil, Ahmet Zeki; Gunduz, OguzhanThree-dimensional (3D) in vitro cell culture models have recently gained increasing interest in predicting the response of anticancer drugs. In this study first, we tried to obtain a novel hyaluronic acid (HA)/gelatin (Gel) modified bacterial cellulose (BC) composite scaffolds by in situ fermentation method. Morphological and chemical structures, wettability, and thermal stability of scaffolds were evaluated. In particular, the human glioblastoma (GBM) cancer cell line (U251) was seeded into BC/HA/Gel scaffolds to evaluate their potential as in vitro 3D cancer cell culture. MTT proliferation assay, scanning electron microscopy, and confocal microscopy were utilised to determine cell proliferation, morphology and adhesion. The results suggest that our hyaluronic acid and gelatin modified bacterial cellulose scaffold is promising to be used as in vitro 3D culture of GBM cells and may be used to predict treatment response or reactions of new therapeutics.