Bioengineering / Biyomühendislik

Permanent URI for this collectionhttps://hdl.handle.net/11147/4529

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A Glucuronoxylan-Based Bio-Ink Development: Characterization and Application
(Wiley, 2023) Yıldırım, Ömer; Arslan Yıldız, Ahu
Bioprinting is a trending technique that enables the fabrication of threedimensional (3D) constructs in designed shapes and with desired properties. Bioinks are one of the most significant components of bioprinting and the successful fabrication of 3D bioprinted constructs mostly depends on the features of bioinks that would be used. New generation bioinks that are soft and viscous enough, printable under low pressure, stable in cell culture, and have fast gelation mechanisms are ideal to be used in current bioprinting techniques. Hydrocolloids have said features and have similar properties to native ECM structures. Hence bioinks that are developed from hydrocolloids can be utilized for mimicking of ECM structure of soft tissues. Polysaccharidebased hydrocolloids are ideal bioink candidates with their high waterholding capacity and biocompatibility. Here, a glucuronoxylanbased newgeneration bioink was developed, and its printability was evaluated for 3D bioprinting applications. The glucuronoxylanbased hydrocolloid was obtained by water extraction of quince seeds and its utilization in bioprinting was investigated. Bioink characterization was done by FTIR and mechanical analysis. Bioprinting parameters were optimized assessing uniformity, pore factor, and shape fidelity. Then, the characterization of bioprinted constructs was performed by pore angle measurement, waterholding capacity analysis, protein adsorption, and cell viability assays. Bioprinted structures have high mechanical strength, suitable protein adsorption behavior, and waterholding capacity as high as 20fold of its own weight, which is higher than other hydrogels that were used in soft tissue engineering. Moreover, the cell viability results of fibroblast cells in the bioink were high for longterm culture. In conclusion, findings show that the developed glucuronoxylanbased bioink is a biocompatible and promising bioink material for further tissue engineering applications.
Biopatterning of 3d Cellular Structures Via Contactless Magnetic Manipulation for Drug Screening
(Mary Ann Liebert, 2023) Onbas, Rabia; Arslan Yıldız, Ahu
Citation - WoS: 1
Citation - Scopus: 1
The 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 Hakan
This 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.image
Citation - WoS: 3
Citation - Scopus: 4
Biopatterning of 3d Cellular Model by Contactless Magnetic Manipulation for Cardiotoxicity Screening
(Mary Ann Liebert, Inc, 2023) Önbaş, Rabia; Arslan Yıldız, Ahu
Patterning 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.
Biofabrication of Scaffold-Free 3d Cellular Structures Using Magnetic Levitational Assembly To Study Cardiac Toxicity
(Mary Ann Liebert, 2023) Yıldız, Ahu Arslan; Arslan Yıldız, Ahu; Onbaş, Rabia
Spheroids are one of the well-characterized 3D cell culture approaches for drug screening and therapeutic studies. Magnetic levitation (MagLev) is a newly developing approach to form 3D cellular structures and spheroids [1,2,3]. Magnetic levitational assembly of cells provides rapid, simple, cost-effective 3D cell culture formation while ensuring scaffold-free microenvironment. Here, our efforts are summarized in designing new magnetic levitation platform and biofabrication of 3D cellular entities via magnetic levitation for tissue engineering. Magnetic levitation and guidance of cells were provided by using a paramagnetic agent to fabricate scaffold-free 3D cellular structures. The parameters of cell density, paramagnetic agent concentration, and culturing time were optimized to obtain 3D cardiac cellular structures with tunable size, circularity, and high cell viability. Cellular and extracellular components of the 3D cellular structures were demonstrated via immunofluorescent staining. Also, 3D cardiac cellular structures showed more resistance to drug exposure compared to 2D control. In conclusion, MagLev methodology offers an easy and efficient way to fabricate 3D cellular structures for drug screening studies.
Biopatterning of 3d Cellular Structures Via Contactless Magnetic Manipulation for Drug Screening
(Mary Ann Liebert, 2023) Önbaş, Rabia; Arslan Yıldız, Ahu
"Patterning and manipulation techniques have been used to fabricate 3D cell cultures in tissue engineering. The contactless magnetic manipulation approach is a rapid, simple, and cost-effective method that requires paramagnetic agents [1-3] or magnetic materials [4]. Here, to obtain patterned 3D cellular structures a new alginate-based bio-ink formulation was developed to fabricate 3D cellular structures using contactless magnetic manipulation. 3D cardiac model was obtained by patterning rat cardiomyocytes. Cellular and extracellular components and cardiac-specific markers of patterned 3D cellular structures were indicated successfully. Drug response of patterned 3D cellular structures was evaluated by applying doxorubicin. Patterned 3D cardiac cellular structures showed significantly different drug response compared to conventional 2D cell cultures. In conclusion, this technique provides an easy, efficient, and low-cost methodology to fabricate 3D cardiac structures for drug screening.
Citation - WoS: 9
Citation - Scopus: 9
Fabrication 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, Ahu
Paper-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.
Citation - WoS: 17
Citation - Scopus: 18
Development of a Hydrocolloid Bio-Ink for 3d Bioprinting
(Royal Society of Chemistry, 2022) Yıldırım, Özüm; Arslan Yıldız, Ahu
A 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.
On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening
(Mary Ann Liebert, 2022) Yıldırım, Özüm; Arslan Yıldız, Ahu
Three-dimensional (3D) cell culture allows cell-cell and cellmatrix interactions and provides more in vivo like models rather than 2D cell culture which cannot fully mimic native tissue. 3D cell culture on microfluidics allows formation of 3D structures that mimic the physiological and chemical microenvironment for cells[1]. These microfluidic platforms also downsize bench-top laboratory to a microchip, require miniaturized reagent, and are convenient for dynamic drug screening[2]. In this study, a microfluidic platform was designed which is housing a PLLCL scaffold fabricated by electrospinning methodology.
Biofabrication by Magnetic Levitational Assembly of Cells Into Defined 3d Cellular Structures
(Mary Ann Liebert, 2022) Arslan Yıldız, Ahu
In the field of tissue engineering 3D (three dimensional) cell culture studies have increased over the years since they are the closest models of real tissues. Compared to the 2D models, there is a big improvement on cell growth, morphology, differentiation, gene and protein expression when 3D system is utilized. Because of these advantages 3D cell culture is commonly used for tissue engineering, artificial organ technologies, regenerative medicine, drug development, drug screening and stem cell studies. Despite promising advances in these areas, there are still unmet needs to completely fulfill all requirements. Sophisticated tools, methodologies and materials are still required for further development in tissue engineering; especially for cellular assembly, single cell level control, easy control over biofabrication system, direct forward cellular imaging and analysis. Recently, magnetic levitation technology that overcomes most of the above mentioned problems, has been utilized for the formation of 3D cellular structures. Magnetic levitational assembly of cells provide rapid, simple, cost-effective 3D cell culture formation while ensuring scaffold-free microenvironment.

Bioengineering / Biyomühendislik

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