Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 17Citation - Scopus: 15Antiproliferative and Apoptotic Effects of Olive Leaf Extract Microcapsules on Mcf-7 and A549 Cancer Cells(American Chemical Society, 2023) Bal, Yıldız; Sürmeli, Yusuf; Şanlı Mohamed, GülşahAlginate microcapsules are a talented means for the delivery of broad curative biomacromolecules. In this study, we immobilized olive leaf extract (OLE) by calcium alginate (CA) and chitosan-coated CA (CCA) and characterized the OLE-loaded CA and CCA. The cytotoxic effect, the cell cycle arrest, and the apoptotic effect of OLE and its microcapsules were investigated against breast adenocarcinoma (MCF-7) and lung carcinoma (A549). As a result, the loading capacity of OLE-CA and OLE-CCA was found to be 80 and 99%, respectively, in optimal conditions. Also, OLE-CA and OLE-CCA were characterized by unique FTIR peaks and morphological display relative to the empty CCA microcapsules. The cytotoxicity analysis showed that the IC50 values of OLE-CA and OLE-CCA were determined to be 312 and 0.94 μg mL-1 against A549, respectively, whereas these were found to be 865.4 and 425.5 μg mL-1 for MCF-7 cells. On the other hand, the OLE microcapsules did not possess in any concentration of cytotoxic influence on the BEAS 2B healthy cell line. Also, the exposure of OLE-CCA to MCF-7 and A549 resulted in the arrest of more MCF-7 and A549 cells at the G0/G1 phase compared to the OLE. A549 and MCF-7 cells were predominantly found in the late apoptosis phase and necrosis phase, respectively. Optical microscopy images confirmed that OLE microcapsules were more effective against MCF-7 and A549 than free OLE. The present work suggested that the OLE microcapsules might be administered as nutrition supplements for cancer therapy. © 2023 The Authors. Published by American Chemical Society.Article Citation - WoS: 2Citation - Scopus: 6Immobilization of Olive Leaf Extract With Chitosan Nanoparticles as an Adjunct To Enhance Cytotoxicity(American Chemical Society, 2023) Özdamar, Burcu; Sürmeli, Yusuf; Şanlı Mohamed, GülşahWe immobilized the olive leaf extract (OLE) with chitosannanoparticles(CNPs) by optimizing the effect of various immobilization conditions,and OLE-loaded CNPs (OLE-CNPs) were then elaborately characterizedphysicochemically by scanning electron microscopy (SEM), Fourier transforminfrared (FT-IR) spectroscopy, dynamic light scattering (DLS), andatomic force microscopy (AFM). Under optimal conditions, CNPs wereable to accommodate the OLE with a loading capacity of 97.5%. Theresulting OLE-CNPs had a spherical morphology, and their average diameterwas approximately 100 nm. The cytotoxic influence, cell cycle distribution,and apoptosis stage of OLE and OLE-CNPs were analyzed on lung carcinoma(A549) and breast adenocarcinoma (MCF-7) cell lines. In an in vitrocytotoxic assay, IC50 values of OLE-CNPs were determinedto be 540 & mu;g/mL for A549 and 810 & mu;g/mL for MCF-7. Thetreatment of both A549 and MCF-7 with OLE-CNPs caused the highestcell arrest in G0/G1 in a dose-independent manner. OLE-CNPs affectedcell cycle distribution in a manner different from free OLE treatmentin both cancer cells. A549 and MCF-7 cells were predominantly foundin the late apoptosis and necrosis phases, respectively, upon treatmentof 1000 & mu;M OLE-CNPs. Our results suggest that CNPs enhance theutility of OLEs as nutraceuticals in cancer and that OLE-CNPs canbe utilized as an adjunct to cancer therapy.Article Citation - WoS: 27Citation - Scopus: 27In Vivo Bone Regeneration Capacity of Multiscale Porous Polycaprolactone-Based High Internal Phase Emulsion (polyhipe) Scaffolds in a Rat Calvarial Defect Model(American Chemical Society, 2023) Aldemir Dikici, Betül; Chen, Min-Chia; Dikici, Serkan; Chiu, Hsien-Chung; Claeyssens, FrederikGlobally, one of the most common tissue transplantationproceduresis bone grafting. Lately, we have reported the development of polymerizedhigh internal phase emulsions (PolyHIPEs) made of photocurable polycaprolactone(4PCLMA) and shown their potential to be used as bone tissue engineeringscaffolds in vitro. However, it is essential to evaluatethe in vivo performance of these scaffolds to investigatetheir potential in a clinically more relevant manner. Therefore, inthis study, we aimed to compare in vivo performancesof macroporous (fabricated using stereolithography), microporous (fabricatedusing emulsion templating), and multiscale porous (fabricated usingemulsion templating and perforation) scaffolds made of 4PCLMA. Also,3D-printed macroporous scaffolds (fabricated using fused depositionmodeling) made of thermoplastic polycaprolactone were used as a control.Scaffolds were implanted into a critical-sized calvarial defect, animalswere sacrificed 4 or 8 weeks after implantation, and the new boneformation was assessed by micro-computed tomography, dental radiography,and histology. Multiscale porous scaffolds that include both micro-and macropores resulted in higher bone regeneration in the defectarea compared to only macroporous or only microporous scaffolds. Whenone-grade porous scaffolds were compared, microporous scaffolds showedbetter performance than macroporous scaffolds in terms of mineralizedbone volume and tissue regeneration. Micro-CT results revealed thatwhile bone volume/tissue volume (Bv/Tv) values were 8 and 17% at weeks4 and 8 for macroporous scaffolds, they were significantly higherfor microporous scaffolds, with values of 26 and 33%, respectively.Taken together, the results reported in this study showed the potentialapplication of multiscale PolyHIPE scaffolds, in particular, as apromising material for bone regeneration.Review Citation - WoS: 52Citation - Scopus: 56Spheroid engineering in microfluidic devices(American Chemical Society, 2023) Tevlek, Atakan; Keçili, Seren; Özçelik, Özge Solmaz; Kulah, Haluk; Tekin, H. CumhurTwo-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.Article Citation - WoS: 76Citation - Scopus: 82Multicolor Emitting Carbon Dot-Reinforced Pva Composites as Edible Food Packaging Films and Coatings With Antimicrobial and Uv-Blocking Properties(American Chemical Society, 2022) Alaş, Melis Özge; Doğan, Gamze; Yalçın, Mustafa Serkan; Özdemir, Sadin; Genç, RükanActive food packaging has become attractive because of the possibility to provide a longer shelf-life by loading functional agents into the packages to maintain the quality of food products. Herein, photoluminescent and transparent polyvinyl alcohol (PVA)-based composites embedding multicolor fluorescent carbon dots (CD/PVA) were prepared by the solvent casting method. The prepared CDs emit a strong and stable fluorescence in solution while the CD/PVA composite films were transparent, flexible, and showed UV-blocking activity with a strong fluorescence emission. Blue color-emitting CDs showed the highest UV blockage at UVA (87.04%), UVB (87.04%), and UVC (92.22%) regions while PVA alone absorbed only less than 25% of the light in all UV regions. UV blockage capacity was shown to be decreased by half, in line with the emission color shift from blue to red. Thermal properties of the PVA film were improved by the addition of CDs to the polymer, and in vitro cell viability tests showed that none of the CDs were cytotoxic against the human lung fibroblast healthy cell line (MRC-F cells) when integrated into the PVA. The antimicrobial activity of CD/PVA nanofilms was qualitatively determined. The prepared films exhibited good antimicrobial activity against both Gram-positive and Gram-negative bacteria with mild antioxidant and metal chelating activity, and significant inhibition of biofilm formation with a strong link with emitted color and the concentration of the composites. Green- and red-emitting CD/PVA with the highest antimicrobial activity were then analyzed and compared with the plane PVA employing their effect on the shelf-life of strawberries as a model for perishable foods. Fresh strawberries dip coated with CD/PVA and PVA were monitored over time, and virtual evaluations showed that CDs/PVA film coating resulted in reduced weight and moisture loss and significantly inhibited the fungal growth and spoiling for over 6 days at RT and 12 days at fridge conditions maintaining the visual appearance and natural color of the fruit. The findings in this work indicated the potential of reported CD as non-cytotoxic, UV-blocking antimicrobial additives for the development of edible coatings and packages for their use in the food industry, as well as pharmaceutical and healthcare applications.Article Citation - WoS: 10Citation - Scopus: 14An Electromechanical Lab-On Platform for Colorimetric Detection of Serum Creatinine(American Chemical Society, 2022) Karakuzu, Betül; Tarım, Ergün Alperay; Öksüz, Cemre; Tekin, Hüseyin CumhurChronic kidney disease (CKD) is a high-cost disease that affects approximately one in ten people globally, progresses rapidly, results in kidney failure or dialysis, and triggers other diseases. Although clinically used serum creatinine tests are used to evaluate kidney functions, these tests are not suitable for frequent and regular control at-home settings that obstruct the regular monitoring of kidney functions, improving CKD management with early intervention. This study introduced a new electromechanical lab-on-a-chip platform for point-of-care detection of serum creatinine levels using colorimetric enzyme-linked immunosorbent assay (ELISA). The platform was composed of a chip containing microreservoirs, a stirring bar coated with creatinine-specific antibodies, and a phone to detect color generated via ELISA protocols to evaluate creatinine levels. An electromechanical system was used to move the stirring bar to different microreservoirs and stir it inside them to capture and detect serum creatinine in the sample. The presented platform allowed automated analysis of creatinine in ~50 min down to ~1 and ~2 mg/dL in phosphate-buffered saline (PBS) and fetal bovine serum (FBS), respectively. Phone camera measurements in hue, saturation, value (HSV) space showed sensitive analysis compared to a benchtop spectrophotometer that could allow low-cost analysis at point-of-care.Article Citation - WoS: 12Citation - Scopus: 12Sema6d Differentially Regulates Proliferation, Migration, and Invasion of Breast Cell Lines(American Chemical Society, 2022) Günyüz, Zehra Elif; Sahi İlhan, Ece; Küçükköse, Cansu; İpekgil, Doğaç; Tok, Güneş; Meşe, Gülistan; Özçivici, Engin; Yalçın Özuysal, ÖzdenSemaphorin 6D (SEMA6D), a member of the class 6 semaphorin family, is a membrane-associated protein that plays a key role in the development of cardiac and neural tissues. A growing body of evidence suggests that SEMA6D is also involved in tumorigenesis. In breast cancer, high SEMA6D levels are correlated with better survival rates. However, very little is known about the functional significance of SEMA6D in breast tumorigenesis. In the present study, we aimed to investigate the effects of SEMA6D expression on the normal breast cell line MCF10A and the breast cancer cell lines MCF7 and MDA MB 231. We demonstrated that SEMA6D expression increases the proliferation of MCF10A cells, whereas the opposite effect was observed in MCF7 cells. SEMA6D expression induced anchorage-independent growth in both cancer cell lines. Furthermore, migration of MCF10A and MCF7 cells and invasion of MDA MB 231 cells were elevated in response to SEMA6D overexpression. Accordingly, the genes related to epithelial-mesenchymal transition (EMT) were altered by SEMA6D expression in MCF10A and MCF7 cell lines. Finally, we provided evidence that SEMA6D levels were associated with the expression of the cell cycle, EMT, and Notch signaling pathway-related genes in breast cancer patients' data. We showed for the first time that SEMA6D overexpression has cell-specific effects on the proliferation, migration, and invasion of normal and cancer breast cell lines, which agrees with the gene expression data of clinical samples. This study lays the groundwork for future research into understanding the functional importance of SEMA6D in breast cancerArticle Citation - WoS: 46Citation - Scopus: 46Thiolene- and Polycaprolactone Methacrylate-Based Polymerized High Internal Phase Emulsion (polyhipe) Scaffolds for Tissue Engineering(American Chemical Society, 2022) Aldemir Dikici, Betül; Malayeri, Atra; Sherborne, Colin; Dikici, Serkan; Paterson, Thomas; Dew, Lindsey; Claeyssens, FrederikHighly porous emulsion templated polymers (PolyHIPEs) provide a number of potential advantages in the fabrication of scaffolds for tissue engineering and regenerative medicine. Porosity enables cell ingrowth and nutrient diffusion within, as well as waste removal from, the scaffold. The properties offered by emulsion templating alone include the provision of high interconnected porosity, and, in combination with additive manufacturing, the opportunity to introduce controlled multiscale porosity to complex or custom structures. However, the majority of monomer systems reported for PolyHIPE preparation are unsuitable for clinical applications as they are nondegradable. Thiol-ene chemistry is a promising route to produce biodegradable photocurable PolyHIPEs for the fabrication of scaffolds using conventional or additive manufacturing methods; however, relatively little research has been reported on this approach. This study reports the groundwork to fabricate thiol- and polycaprolactone (PCL)-based PolyHIPE materials via a photoinitiated thiolene click reaction. Two different formulations, either three-arm PCL methacrylate (3PCLMA) or four-arm PCL methacrylate (4PCLMA) moieties, were used in the PolyHIPE formulation. Biocompatibility of the PolyHIPEs was investigated using human dermal fibroblasts (HDFs) and human osteosarcoma cell line (MG-63) by DNA quantification assay, and developed PolyHIPEs were shown to be capable of supporting cell attachment and viability.Article Citation - WoS: 24Citation - Scopus: 30Hologlev: a Hybrid Magnetic Levitation Platform Integrated With Lensless Holographic Microscopy for Density-Based Cell Analysis(American Chemical Society, 2021) Delikoyun, Kerem; Yaman, Sena; Yılmaz, Esra; Sarıgil, Öykü; Anıl İnevi, Müge; Telli, Kübra; Yalçın Özuysal, ÖzdenIn clinical practice, a variety of diagnostic applications require the identification of target cells. Density has been used as a physical marker to distinguish cell populations since metabolic activities could alter the cell densities. Magnetic levitation offers great promise for separating cells at the single cell level within heterogeneous populations with respect to cell densities. Traditional magnetic levitation platforms need bulky and precise optical microscopes to visualize levitated cells. Moreover, the evaluation process of cell densities is cumbersome, which also requires trained personnel for operation. In this work, we introduce a device (HologLev) as a fusion of the magnetic levitation principle and lensless digital inline holographic microscopy (LDIHM). LDIHM provides ease of use by getting rid of bulky and expensive optics. By placing an imaging sensor just beneath the microcapillary channel without any lenses, recorded holograms are processed for determining cell densities through a fully automated digital image processing scheme. The device costs less than $100 and has a compact design that can fit into a pocket. We perform viability tests on the device by levitating three different cell lines (MDA-MB-231, U937, D1 ORL UVA) and comparing them against their dead correspondents. We also tested the differentiation of mouse osteoblastic (7F2) cells by monitoring characteristic variations in their density. Last, the response of MDA-MB-231 cancer cells to a chemotherapy drug was demonstrated in our platform. HologLev provides cost-effective, label-free, fully automated cell analysis in a compact design that could be highly desirable for laboratory and point-of-care testing applications.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.