Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 1Citation - Scopus: 1The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots(Wiley, 2024) Yücel, Müge; Onbaş, Rabia; Arslan Yıldız, Ahu; Yıldız, Ümit HakanThis study describes the formation, size control, and penetration behavior of polymer nanodots (Pdots) consisting of single or few chain polythiophene-based conjugated polyelectrolytes (CPEs) via nanophase separation between good solvent and poor solvent of CPE. Though the chain singularity may be associated with dilution nanophase separation suggests that molecules of a good solvent create a thermodynamically driven solvation layer surrounding the CPEs and thereby separating the single chains even in their poor solvents. This statement is therefore corroborated with emission intensity/lifetime, particle size, and scattering intensity of polyelectrolyte in good and poor solvents. Regarding the augmented features, Pdots are implemented into cell imaging studies to understand the nuclear penetration and to differentiate the invasive characteristics of breast cancer cells. The python based red, green, blue (RGB) color analysis depicts that Pdots have more nuclear penetration ability in triple negative breast cancer cells due to the different nuclear morphology in shape and composition and Pdots have penetrated cell membrane as well as extracellular matrix in spheroid models. The current Pdot protocol and its utilization in cancer cell imaging are holding great promise for gene/drug delivery to target cancer cells by explicitly achieving the very first priority of nuclear intake. The penetration capability of cationic soft nanodots in to tumor models of breast cancer is demonstrated. The image analysis based on fluorescence intensity variation reveals the characteristics of translocation of nanodots in dense mediums such as tumor models.imageArticle Citation - WoS: 3Citation - Scopus: 4Biopatterning of 3d Cellular Model by Contactless Magnetic Manipulation for Cardiotoxicity Screening(Mary Ann Liebert, Inc, 2023) Önbaş, Rabia; Arslan Yıldız, AhuPatterning cells to create three-dimensional (3D) cell culture models by magnetic manipulation is a promising technique, which is rapid, simple, and cost-effective. This study introduces a new biopatterning approach based on magnetic manipulation of cells with a bioink that consists alginate, cells, and magnetic nanoparticles. Plackett-Burman and Box-Behnken experimental design models were used to optimize bioink formulation where NIH-3T3 cells were utilized as a model cell line. The patterning capability was confirmed by light microscopy through 7 days culture time. Then, biopatterned 3D cardiac structures were formed using H9c2 cardiomyocyte cells. Cellular and extracellular components, F-actin and collagen Type I, and cardiac-specific biomarkers, Troponin T and MYH6, of biopatterned 3D cardiac structures were observed successfully. Moreover, Doxorubicin (DOX)-induced cardiotoxicity was investigated for developed 3D model, and IC50 value was calculated as 8.1 μM for biopatterned 3D cardiac structures, which showed higher resistance against DOX-exposure compared to conventional two-dimensional cell culture. Hereby, developed biopatterning methodology proved to be a simple and rapid approach to fabricate 3D cardiac models, especially for drug screening applications. Copyright 2023, Mary Ann Liebert, Inc., publishers.Article Citation - WoS: 9Citation - Scopus: 9Fabrication and Development of a Microfluidic Paper-Based Immunosorbent Assay Platform (μpisa) for Colorimetric Detection of Hepatitis C(Royal Society of Chemistry, 2023) Özefe, Fatih; Arslan Yıldız, AhuPaper-based microfluidics is an emerging analysis tool used in various applications, especially in point-of-care (PoC) diagnostic applications, due to its advantages over other types of microfluidic devices in terms of simplicity in both production and operation, cost-effectiveness, rapid response time, low sample consumption, biocompatibility, and ease of disposal. Recently, various techniques have been developed and utilized for the fabrication of paper-based microfluidics, such as photolithography, micro-embossing, wax and PDMS printing, etc. In this study, we offer a fabrication methodology for a microfluidic paper-based immunosorbent assay (μPISA) platform and the detection of Hepatitis C Virus (HCV) was carried out to validate this platform. A laser ablation technique was utilized to form hydrophobic barriers easily and rapidly, which was the major advantage of the developed fabrication methodology. The characterization of the μPISA platform was performed in terms of micro-channel properties using bright-field (BF) microscopy, and surface properties using scanning electron microscopy (SEM). At the same time, sample volume and liquid handling capacity were analyzed quantitatively. Ablation speed (S) and laser power (P) were optimized, and it was shown that one combination (10P60S) provided minimal deviation in micro-channel dimensions and prevented deterioration of hydrophobic barriers. Also, the minimum hydrophobic barrier width, which prevents cross-barrier bleeding, was determined to be 255.92 ± 10.01 μm. Furthermore, colorimetric HCV NS3 detection was implemented to optimize and validate the μPISA platform. Here, HCV NS3 in both PBS and human blood plasma was successfully detected by the naked eye at concentrations as low as 1 ng mL−1 and 10 ng mL−1, respectively. Moreover, the limit of detection (LoD) values for HCV NS3 were acquired as 0.796 ng mL−1 in PBS and 2.203 ng mL−1 in human blood plasma with a turnaround time of 90 min. In comparison with conventional ELISA, highly sensitive and rapid HCV NS3 detection was accomplished colorimetrically on the developed μPISA platform.Article Citation - WoS: 17Citation - Scopus: 18Development of a Hydrocolloid Bio-Ink for 3d Bioprinting(Royal Society of Chemistry, 2022) Yıldırım, Özüm; Arslan Yıldız, AhuA new generation of bio-inks that are soft, viscous enough, stable in cell culture, and printable at low printing pressures is required in the current state of 3D bioprinting technology. Hydrogels can meet these features and can mimic the microenvironment of soft tissues easily. Hydrocolloids are a group of hydrogels which have a suitable gelling capacity and rheological properties. According to the literature, polysaccharide-based hydrocolloids are used in the food industry, wound healing technologies, and tissue engineering. Quince seed hydrocolloids (QSHs), which consist of mostly glucuronoxylan, can easily be obtained from quince seeds by water extraction. In this study, the use of a QSH as a bio-ink was investigated. The suitability of QSH for the printing process was assessed by rheological, uniformity and pore factor analyses. Appropriate printing parameters were determined and the characterization of the bioprinted QSHs was performed by SEM analysis, water uptake capacity measurement, and protein adsorption assay. The bioprinted QSHs had excellent water uptake capacity and showed suitable protein adsorption behaviour. Analyses of the biocompatibility and cellular viability of bioprinted QSHs were conducted using NIH-3T3 fibroblast cells and the results were found to be high during short and long-term cell culture periods. It was proved that QSH is a highly promising bio-ink for 3D bioprinting and further tissue engineering applications.Article Citation - WoS: 43Citation - Scopus: 46Glucuronoxylan-Based Quince Seed Hydrogel: a Promising Scaffold for Tissue Engineering Applications(Elsevier, 2021) Güzelgülgen, Meltem; Özkendir İnanç, Dilce; Yıldız, Ümit Hakan; Arslan Yıldız, AhuNatural gums and mucilages from plant-derived polysaccharides are potential candidates for a tissue-engineering scaffold by their ability of gelation and biocompatibility. Herein, we utilized Glucuron-oxylanbased quince seed hydrogel (QSH) as a scaffold for tissue engineering applications. Optimization of QSH gelation was conducted by varying QSH and crosslinker glutaraldehyde (GTA) concentrations. Structural characterization of QSH was done by Fourier Transform Infrared Spectroscopy (MR). Furthermore, morphological and mechanical investigation of QSH was performed by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The protein adsorption test revealed the suitability of QSH for cell attachment. Biocompatibility of QSH was confirmed by culturing NIH-3T3 mouse fibroblast cells on it. Cell viability and proliferation results revealed that optimum parameters for cell viability were 2 mg mi(-1)of QSH and 0.03 M GTA. SEM and DAPI staining results indicated the formation of spheroids with a diameter of approximately 300 pm. Furthermore, formation of extracellular matrix (ECM) microenvironment was confirmed with the Collagen Type-I staining. Here, it was demonstrated that the fabricated QSH is a promising scaffold for 3D cell culture and tissue engineering applications provided by its highly porous structure, remarkable swelling capacity and high biocompatibility. (C) 2021 Published by Elsevier B.V.Article Citation - WoS: 16Citation - Scopus: 13Fabrication of Tunable 3d Cellular Structures in High Volume Using Magnetic Levitation Guided Assembly(American Chemical Society, 2021) Onbas, Rabia; Arslan Yıldız, AhuTunable and reproducible size with high circularity is an important limitation to obtain three-dimensional (3D) cellular structures and spheroids in scaffold free tissue engineering approaches. Here, we present a facile methodology based on magnetic levitation (MagLev) to fabricate 3D cellular structures rapidly and easily in high-volume and low magnetic field. In this study, 3D cellular structures were fabricated using magnetic levitation directed assembly where cells are suspended and self-assembled by contactless magnetic manipulation in the presence of a paramagnetic agent. The effect of cell seeding density, culture time, and paramagnetic agent concentration on the formation of 3D cellular structures was evaluated for NIH/3T3 mouse fibroblast cells. In addition, magnetic levitation guided cellular assembly and 3D tumor spheroid formation was examined for five different cancer cell lines: MCF7 (human epithelial breast adenocarcinoma), MDA-MB-231 (human epithelial breast adenocarcinoma), SHSYSY (human bone-marrow neuroblastoma), PC-12 (rat adrenal gland pheochromocytoma), and HeLa (human epithelial cervix adenocarcinoma). Moreover, formation of a 3D coculture model was successfully observed by using MDA-MB-231 dsRED and MDA-MB-231 GFP cells. Taken together, these results indicate that the developed MagLev setup provides an easy and efficient way to fabricate 3D cellular structures and may be a feasible alternative to conventional methodologies for cellular/multicellular studies.Correction Citation - WoS: 2Citation - Scopus: 2Correction: Scaffold-Free Three-Dimensional Cell Culturing Using Magnetic Levitation(Royal Society of Chemistry, 2018) Türker, Esra; Demircak, Nida; Arslan Yıldız, AhuThe authors regret the inclusion of an incorrect figure caption for Fig. 2. The corrected figure caption for Fig. 2 is shown below. Fig. 2 Evaluation of levitation height (z) and density profiles through magnetic levitation. (A) Gd(III) chelates were named as Gx (Gadovist/Gadobutrol), Dx (Dotarem/Gadoteric acid) and Ox (Omniscan/Gadodiamide). (B) Standard curve for PE bead density against levitation height; linear curve fitting gives the standard function for the corresponding curve. (C–E) Levitation height profiles of single NIH 3T3 cells under 30/50/100/200 mM Gd concentrations. Single cell density profiles calculated through standard function of linear fitting.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: 75Citation - Scopus: 74Scaffold-Free Three-Dimensional Cell Culturing Using Magnetic Levitation(Royal Society of Chemistry, 2018) Türker, Esra; Demirçak, Nida; Arslan Yıldız, AhuThree-dimensional (3D) cell culture has emerged as a pioneering methodology and is increasingly utilized for tissue engineering, 3D bioprinting, cancer model studies and drug development studies. The 3D cell culture methodology provides artificial and functional cellular constructs serving as a modular playground prior to animal model studies, which saves substantial efforts, time and experimental costs. The major drawback of current 3D cell culture methods is their dependency on biocompatible scaffolds, which often require tedious syntheses and fabrication steps. Herein, we report an easy-to-use methodology for the formation of scaffold-free 3D cell culture and cellular assembly via magnetic levitation in the presence of paramagnetic agents. To paramagnetize the cell culture environment, three different Gadolinium(iii) chelates were utilized, which led to levitation and assembly of cells at a certain levitation height. The assembly and close interaction of cells at the levitation height where the magnetic force was equilibrated with gravitational force triggered the formation of complex 3D cellular structures. It was shown that Gd(iii) chelates provided an optimal levitation that induced intercellular interactions in scaffold-free format without compromising cell viability. NIH 3T3 mouse fibroblasts and HCC827 non-small-cell lung cancer cells were evaluated via the magnetic levitation system, and the formation of 3D cell culture models was validated for both cell lines. Hereby, the developed magnetic levitation system holds promises for complex cellular assemblies and 3D cell culture studies.Article Citation - WoS: 46Citation - Scopus: 57Recent Advances in Magnetic Levitation: a Biological Approach From Diagnostics To Tissue Engineering(American Chemical Society, 2018) Türker, Esra; Arslan Yıldız, AhuThe magnetic levitation technique has been utilized to orientate and manipulate objects both in two dimensions (2D) and three dimensions (3D) to form complex structures by combining various types of materials. Magnetic manipulation holds great promise for several applications such as self-assembly of soft substances and biological building blocks, manipulated tissue engineering, as well as cell or biological molecule sorting for diagnostic purposes. Recent studies are proving the potential of magnetic levitation as an emerging tool in biotechnology. This review outlines the advances of newly developing magnetic levitation technology on biological applications in aqueous environment from the biotechnology perspective.