Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Annotation On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening(2022) Yıldırım, Özüm; Arslan Yıldız, AhuResearch Project Manyetik levitasyon yöntemiyle kemik hücrelerinin ağırlıksız ortamda kültürlenmesi(2019) Tekin, Hüseyin Cumhur; Arslan Yıldız, Ahu; Özçivici, EnginMekanik kuvvetler canlılarda özellikle kas ve kemik dokularının sağlıklı formlarda bulunmasında ve fonksiyonlarını yerine getirmesinde önemli rol oynarlar. Mekanik kuvvetlerin kısmen ya da tamamen ortadan kalktığı felç, yatalaklık, yaşlılık ve yerçekimsiz ortam koşulları kas ve kemik dokusunda ciddi miktarda kayıplar meydana getirmektedir. Kemik doku kayıplarına ek olarak mekanik yüklenmenin ortadan kalkması kemik iliğinde bulunan ve kemik hücre havuzunu oluşturan mezenkimal kök hücrelerin yağ yönelimine girmelerine ve kemik iliğinin aşırı miktarda yağlanmasına sebep olur. Bu durum kemiklerde kırılma riskini arttırır. Ayrıca yağ yönelimine bir kez giren kök hücreler kronik olarak tekrar kemik oluşturmaya, dolayısıyla rejenerasyona kolayca yönelemezler. Yaşam koşulları ya da ilerleyen yaş sebebiyle bir insanın kemik kütlesini kaybedip yağ kütlesi kazanmasının birey ve toplum için ciddi bir sosyo-ekonomik maliyeti vardır. Modern toplumda yaş ortalaması artıp hareket ihtiyacı azalırken, kemik erimesi (osteoporoz) ve şişmanlık (obezite) oranlarında da bir artış görülmekte ve bu hastalıkların tedavisi için gereken maddi kaynaklar toplum refahını kısıtlamaktadır. Bu durumla mücadele edebilmek için tedaviye yönelik biyomedikal yaklaşımların geliştirilmesi gerekmektedir. Mekanik kuvvet yoksunluğu ile kemik erimesinin arasındaki ilişkinin incelenmesi için günümüzde gönüllü yatalaklık, fiziksel sınırlama ve kasılmayı önleyici ajanların kullanılması gibi yöntemler tercih edilmektedir. Ancak bu teknikler uygulama zorluğu ve barındırdığı etik problemler dolayısı ile verimli olarak kullanılamamaktadır. Bunun yanı sıra da hücre bazındaki mekanik kuvvet yoksunluğu veya ağırlıksız ortam çalışmaları pahalı uzay uçuşları veya biyoreaktör sistemlerine olan gereksinimden dolayı detaylı olarak gerçekleştirilememektedir. Son yıllarda temel amacı hücre ayrıştırma olarak geliştirilen manyetik levitasyon tekniği kemik hücrelerinin ağırlıksız ortamda incelenebilmesi için oldukça önemli bir fırsat yaratmıştır. Bu projenin amacı manyetik levitasyon prensibini kullanarak kemik ve kemik iliği hücrelerini ağırlıksız ortamda kültürleyerek, oluşan moleküler ve hücresel değişimleri kısa ve uzun vadeli olarak incelemektir. Bu amaca ulaşmak için hücre kültürü sırasında besiyeri ortamı Gadolinyum iyonları kullanılarak paramanyetik hale getirilmiş ve hücreler iki adet neodymium mıknatısın yaratacağı manyetik ortamda ağırlık vektörleri sıfırlanmış şekilde asılı kalmıştır. Projenin sonuçlanması ile manyetik levitasyon tekniği ile ağırlıksız ortamda kemik hücre kültürü teknolojisi geliştirilmiş olacak, ayrıca kemik hücrelerinin ağırlıksız ortamda verdikleri hücresel ve moleküler yanıtların kolay ve ucuz bir şekilde incelenmesi sağlanmıştır.Conference Object On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening(Mary Ann Liebert, 2022) Yıldırım, Özüm; Arslan Yıldız, AhuThree-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, AhuIn 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, AhuBioprinting 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.Conference Object Development of 3d Cardiac Models Via Magnetic Manipulation for Drug Screening Studies(Mary Ann Liebert, 2022) Önbaş, Rabia; Arslan Yıldız, AhuDrug discovery and development process comprise of preclinical and clinical phases that are very intensive, long, and expensive research phases. However, drug candidates can fail in clinical trials. Toxicity is the major reason that leads to about 30% of drug development failures. Recently, the withdrawal rate of drugs from the market was increased to 33.3%from5.1%due to cardiotoxicity. When the drug fails at phase I, the reasons are probably related to 2-dimensional (2D) cell culture studies that do not represent the real tissue physiology; therefore, they provide misdirected data about the efficacy and toxicity of drug.Article Citation - Scopus: 6Sensitive and Rapid Protein Assay Via Magnetic Levitation(Elsevier, 2022) Sözmen, Alper Baran; Arslan Yıldız, AhuMagnetic levitation (MagLev) is a newly emerging methodology for biosensing that provides a density-based analysis, which is highly sensitive and versatile. In this study, a magnetic levitation based sensor platform was used for protein detection; and sensor platform optimization was performed for both sensitivity and resolution. Bovine Serum Albumin (BSA) was used as a model protein and detection of BSA was carried out by antibody functionalized polystyrene microspheres (PSMs). Various sizes of PSMs were examined and their performances were compared by statistical analyses in terms of limit of detection (LOD), sensitivity, and resolution. Quantification of the protein was done based on the magnetic levitation height differences of antibody functionalized PSMs. For optimization of the methodology, varied PSMs were utilized, and standardization of PSM diameter, concentration of the antibody to be functionalized, and PSM dilution rates were carried out. In conclusion, 20 μm PSMs diluted to 0.005% W/V and functionalized with anti-BSA antibody at a concentration of 28 μg/ml were determined to provide the best resolution for BSA detection. A dynamic range of 100 nM to 1 mM was observed with an LOD value of 4.1 ng/ml. This sensing platform promises a novel approach with a diverse application field and it provides rapid, consistent, and reproducible results with high resolution and sensitivity.Conference Object Immobilized Gold Nanoparticle Based Plasmonic Assay Platform for Biomolecule and Microorganism Detection(Wiley, 2021) Sözmen, Alper Baran; Arslan Yıldız, AhuPlasmonic sensors are suitable tools for study of molecular interactions. Localized Surface Plasmon Resonance (LSPR) based sensors detect spectral changes associated with intramolecular interactions between analyte molecules and recognition elements. Due to its labelfree and highly sensitive features, LSPR based methods have high potential for biosensing applications. In this study, we aim to develop a sensitive, labelfree, rapid and simple biosensing platform. For this purpose, a novel refractive index (RI) sensitivity enhancement methodology is proposed by immobilizing gold nanoparticles (GNPs) for platformbased LSPR. Fabrication of platform was carried out by GNP synthesis, immobilization of GNPs on polystyrene solid support, and growth of GNPs. Validation of response to RI changes of developed sensor platform was carried out by tests with varying concentrations of sucrose and ethanol. Then as a proofofconcept, detection ability and detection limit determination of E.coli BL21 (DE3) and protein Bovine Serum Albumin (BSA) was carried out. Adsorption of E.coli BL21 (DE3) via bulk interactions showed that the developed LSPR platform exhibit high enough binding affinity for bacteria detection, and was able to detect down to concentrations as low as 102 CFU/ml. Immune capturing of BSA via antiBSA antibody showed that the developed LSPR platform was able to detect BSA protein–antibody interaction down to 10 µM concentration range.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.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.