Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Conference Object A Glucuronoxylan-Based Bio-Ink Development: Characterization and Application(Wiley, 2023) Yıldırım, Ömer; Arslan Yıldız, AhuBioprinting 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.Conference Object Biopatterning of 3d Cellular Structures Via Contactless Magnetic Manipulation for Drug Screening(Mary Ann Liebert, 2023) Onbas, Rabia; Arslan Yıldız, AhuArticle 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.Conference Object 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, RabiaSpheroids 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.Conference Object 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.Book Part Citation - Scopus: 2Bioprinting of Hydrogels for Tissue Engineering and Drug Screening Applications(Elsevier, 2022) Özmen, Ece; Yıldırım, Özüm; Arslan Yıldız, AhuIn tissue engineering, the 3-dimensional (3D) bioprinting method that enables the production of 3D structures by combining bioinks and cells has become one of the most promising technique. Over the last few years, 3D cell culture models gained importance in the development of disease model and drug development studies. The successful production of the 3D structures by 3D bioprinting mostly depends on the properties of the bioink to be used. Hydrogels, which are natural or synthetic polymers, are generally preferred as bioink materials with their high swelling ability, biocompatibility, biodegradability, and easy gelation ability. The convenience of hydrogels for varied bioprinting applications make them proper bioink materials for bioprinting of artificial tissues, tumor models, and tissue grafts. Bioprinting of functional tissues is successfully performed for years, and hydrogels are utilized as bioink in bone, vascular, neural, cartilage, cardiac, skin tissue engineering, and drug screening. In this chapter, bioprinting methodology, bioinks, hydrogel bioinks, and their applications are discussed in detail. © 2023 Elsevier Inc. All rights reserved.Article Citation - WoS: 8Citation - Scopus: 11Cost-Effective and Rapid Prototyping of Pmma Microfluidic Device Via Polymer-Assisted Bonding(Springer, 2021) Sözmen, Alper Baran; Arslan Yıldız, AhuMicrofluidic systems are relatively new technology field with a constant need of novel and practical manufacturing materials and methods. One of the main shortcomings of current methods is the inability to provide rapid bonding, with high bonding strength, and sound microchannel integrity. Herein we propose a novel method of assembly that overcomes the mentioned limitations. Polymer-assisted bonding is a novel, rapid, simple, and inexpensive method where a polymer is solubilized in a solvent and the constituted solution is used as a bonding agent. In this study, we combined this method with utilization of several phase-changing materials (PCMs) as channel-protective agents. Glauber's salt appeared to be more suitable as a channel-protective agent compared to rest of the salts that have been used in this study. Based on the bonding strength, quality analyses, leakage tests, and SEM imaging, the superior assisting bonding solvent was determined to be dichloromethane with a PMMA concentration of 2.5% (W/V). It showed a bonding strength of 23.794 MPa and a nearly non-visible bonding layer formation of 2.83 mu m in width which is proved by SEM imaging. The said combination of PCM, solvent, and polymer concentration also showed success in leakage tests and an application of micro-droplet generator fabrication. The application was carried out to test the applicability of developed prototyping methodology, which resulted in conclusive outcomes as the droplet generator simulation run in COMSOL Multiphysics version 5.1 software. In conclusion, the developed fabrication method promises simple, rapid, and strong bonding with sharp and clear micro-channel engraving.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.Article Citation - WoS: 27Citation - Scopus: 28Biocomposite Scaffolds for 3d Cell Culture: Propolis Enriched Polyvinyl Alcohol Nanofibers Favoring Cell Adhesion(John Wiley and Sons Inc., 2021) Bilginer, Rumeysa; Özkendir İnanç, Dilce; Yıldız, Ümit Hakan; Arslan Yıldız, AhuThe objective of this work is generation of propolis/polyvinyl alcohol (PVA) scaffold by electrospinning for 3D cell culture. Here, PVA used as co-spinning agent since propolis alone cannot be easily processed by electrospinning methodology. Propolis takes charge in maximizing biological aspect of scaffold to facilitate cell attachment and proliferation. Morphological analysis showed size of the electrospun nanofibers varied between 172-523 nm and 345-687 nm in diameter, for non-crosslinked and crosslinked scaffolds, respectively. Incorporation of propolis resulted in desired surface properties of hybrid matrix, where hybrid scaffolds highly favored protein adsorption. To examine cell compatibility, NIH-3T3 and HeLa cells were seeded on propolis/PVA hybrid scaffold. Results confirmed that integration of propolis supported cell adhesion and cell proliferation. Also, results indicated electrospun propolis/PVA hybrid scaffold provide suitable microenvironment for cell culturing. Therefore, developed hybrid scaffold could be considered as potential candidate for 3D cell culture and tissue engineering.