Person: YILMAZ, BETÜL
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YILMAZ
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BETÜL
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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 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 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.