WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Review Citation - WoS: 52Citation - Scopus: 56Spheroid engineering in microfluidic devices(American Chemical Society, 2023) Tevlek, Atakan; Tekin, Hüseyin Cumhur; Keçili, Seren; Özçelik, Özge Solmaz; Kulah, Haluk; Tekin, H. Cumhur; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyTwo-dimensional (2D) cell culture techniques are commonly employed to investigate biophysical and biochemical cellular responses. However, these culture methods, having monolayer cells, lack cell-cell and cell-extracellular matrix interactions, mimicking the cell microenvironment and multicellular organization. Three-dimensional (3D) cell culture methods enable equal transportation of nutrients, gas, and growth factors among cells and their microenvironment. Therefore, 3D cultures show similar cell proliferation, apoptosis, and differentiation properties to in vivo. A spheroid is defined as self-assembled 3D cell aggregates, and it closely mimics a cell microenvironment in vitro thanks to cell-cell/matrix interactions, which enables its use in several important applications in medical and clinical research. To fabricate a spheroid, conventional methods such as liquid overlay, hanging drop, and so forth are available. However, these labor-intensive methods result in low-throughput fabrication and uncontrollable spheroid sizes. On the other hand, microfluidic methods enable inexpensive and rapid fabrication of spheroids with high precision. Furthermore, fabricated spheroids can also be cultured in microfluidic devices for controllable cell perfusion, simulation of fluid shear effects, and mimicking of the microenvironment-like in vivo conditions. This review focuses on recent microfluidic spheroid fabrication techniques and also organ-on-a-chip applications of spheroids, which are used in different disease modeling and drug development studies.Conference Object Development of Novel Nanotoxicity Assessment Method Utilizing 3d Printing System(Elsevier, 2022) Öksel Karakuş, Ceyda; Aldemir Dikici, Betül; Aldemir Dikici, Betül; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyUnique physicochemical properties of nanomaterials (NMs) make them a material of choice in various applications but also raise concerns about their potential toxicity. While the commercial use of nano-enabled materials is growing rapidly, their interaction with biological systems and environment are not yet fully understood [1, 2]. Traditionally, toxicity of nano-sized materials are assessed by 2D cell culture models due to their time and cost-related advantages but their simplicity often comes at the cost of accuracy. While these methods are considered as the first step in toxicological assessment of both nanosized and bulk-form materials, they fall short in mimicking the complexity of in vivo physiological environments.Conference Object On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening(Mary Ann Liebert, 2022) Arslan Yıldız, Ahu; Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyThree-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.Conference Object Biofabrication by Magnetic Levitational Assembly of Cells Into Defined 3d Cellular Structures(Mary Ann Liebert, 2022) Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyIn 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.Conference Object Development of New Generation Hydrocolloid Bio-Ink for 3d Bioprinting(Mary Ann Liebert, 2022) Arslan Yıldız, Ahu; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyBioprinting enables the production of 3-dimensional (3D) structures by combining bioinks, living cells, extracellular matrix (ECM) components, biochemical factors, proteins, drugs; and it has recently become one of the most promising techniques in the field of tissue engineering. The successful production of the 3D structure to be created by 3D bioprinting technology depends on the properties of the bio-ink to be used. Hydrogel/hydrocolloid materials used as bio-inks are developed using synthetic and natural polymers where they have the necessary rheological properties for printing, they also have biocompatibility, low toxicity and support for cell attachment. Natural hydrogels, which have the ability to mimic the extracellular matrix structure and function at a high rate, are highly preferred bioink materials for bioprinting applications.Article Citation - WoS: 5Citation - Scopus: 5Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2d) and Three-Dimensional (3d) Models for Breast Cancer(Galenos Publishing House, 2021) Aydın,M.; Özdemir, Ekrem; Kılıç Özdemir, Sevgi; Kılıç,S.; Aktaş,S.; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyObjective: Liposomal cancer treatment strategies are useful in removing the side effects that were the main concern in recent years. In this study, we prepared microbubble (MBs) conjugated with DOX-loaded liposomes (DOX-loaded MBs) and investigated their effectiveness in in vitro breast cancer cells in two dimensions (2D) and three dimensions (3D). Materials and Methods: With this aim, breast cancer cells with different features (4T1, MDA-MB231, MCF-7) were growth in 2D and 3D dimensions. The cytotoxic and cell death effects under different conditions, durations and doses were evaluated with WST-1, trypan-blue, colony counts. Apoptotic effects were investigated with flow cytometric Annexin-V-PI and immunohistochemical (Ki-67, caspase 3, 8, 9) methods. Results: After free DOX and LipoDOX were applied, the proliferation index of three cell lines reduced. Intrinsic and extrinsic apoptotic pathways were activated in both 2D and 3D models. However, this effect was observed at lower levels in the 3D model due to the difficulty of diffusion of DOX into the spheroids. Additionally, the suitability of the 3D model for breast cancer cells was supported by formation of ductus-like structures and spheroids. Cell deaths were not observed significantly with the DOX-loaded microbubbles due to rising of MBs to the surface and not reaching spheroids held in matrigel of 3D model. Conclusion: DOX and LipoDOX showed anti-proliferative and apoptosis-inducing effects in breast cancer cells. However, these effects indicated variability depending on the cell lines and 2D or 3D model types. ©Copyright 2021 by the the Turkish Federation of Breast Diseases Societies.Article Citation - WoS: 43Citation - Scopus: 46Glucuronoxylan-Based Quince Seed Hydrogel: a Promising Scaffold for Tissue Engineering Applications(Elsevier, 2021) Güzelgülgen, Meltem; Güzelgülgen, Meltem; Özkendir İnanç, Dilce; Yıldız, Ümit Hakan; Yıldız, Ümit Hakan; Arslan Yıldız, Ahu; Arslan Yıldız, Ahu; 04.01. Department of Chemistry; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 04. Faculty of ScienceNatural 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: 10Citation - Scopus: 11A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices(Elsevier, 2020) Gökçe, Begüm; Çağır, Ali; Akçok, İsmail; Pesen Okvur, Devrim; Çağır, Ali; Pesen Okvur, Devrim; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyDrug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.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, Ahu; Arslan Yıldız, Ahu; Türker, Esra; 03.01. Department of Bioengineering; 01.01. Units Affiliated to the Rectorate; 01. Izmir Institute of Technology; 03. Faculty of EngineeringThe 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.Conference Object Üç Boyutlu Hücre Kültürü için Polimer Esaslı Ekstrasellüler Matriks Mimetiği(Institute of Electrical and Electronics Engineers Inc., 2017) Türker, Esra; Yıldız, Ümit Hakan; Yıldız, Ümit Hakan; Türker, Esra; Arslan Yıldız, Ahu; 04.01. Department of Chemistry; 03.01. Department of Bioengineering; 01.01. Units Affiliated to the Rectorate; 01. Izmir Institute of Technology; 03. Faculty of Engineering; 04. Faculty of ScienceElektro-eğirme metodu gelişmiş üretim teknolojilerindendir ve biyomedikal uygulamalarında yaygın olarak kullanılmaktadır. Özellikle doku mühendisliğinde amaç, çalışılacak doku üzerine doğal veya sentetik destek materyali (iskele) üreterek hücrenin uyum sağlayabileceği bir ortam oluşturmaktır. Bu projenin amacı üç boyutlu (3D) hücre kültürü çalışmaları için elektro-eğirme-metodu ile poli(L-laktik-co-epsilon-kaprolakton) (PLLCL) kullanılarak iskele üretilmesidir. Homojen lifler ve uygun gözenek boyutu elde etmek amacıyla optimizasyon çalışmaları yapılmıştır. Elde edilen liflerin çapı, akış hızı ve voltajın artmasıyla azalmaktadır. Taramalı uç elektron mikroskop incelemeleri (SEM) lif morfolojik yapılarının doku iskelesi fabrikasyonu için ideale yakın olduğunu ortaya çıkarmıştır.