Bioengineering / Biyomühendislik

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2’-Methylklavuzon Causes Lipid-Lowering Effects on A549 Non-Small Cell Lung Cancer Cells and Significant Changes on Dna Structure Evidenced by Fourier Transform Infrared Spectroscopy
(Elsevier, 2020) Ceylan, Çağatay; Aksoy, Hatice Nurdan; Çağır, Ali; Çetinkaya, Hakkı
Various chemical agents are used in the treatment of Non-Small Cell Lung Cancer (NSCLC). 2?-methylklavuzon was proposed as a potential chemotherapeutic agent in cancer treatment based on its topoisomerase inhibition activity. In this study the cellular effects of 2?-methylklavuzon was evaluated on A549 cancer cells using FTIR spectroscopy. 2?-methylklavuzon induced significant changes on both the whole cell lyophilizates and the lipid extracts of the A549 lung cancer cells. 2?-methylklavuzon caused significant structural changes in A549 cell DNA structure: T, A and G DNA breathing modes are lost after the drug application indicating the loss of topoisomerase activity. The level of transcription and RNA synthesis was enhanced. 2?-methylklavuzon induced single stranded DNA formation evidenced by the increase in the ratio of asymmetric/symmetric phosphate stretching modes. 2?-methylklavuzon induced band shifts only in the asymmetric mode of phosphate bonds not in the symmetrical phosphate bond stretching. 2?-methylklavuzon induced A form of DNA topography. In addition to the changes in the DNA structure and transcription 2?-methylklavuzon also caused lipid-lowering effect in A549 cancer cells. 2?-methylklavuzon suppressed lipid unsaturation, however, it induced formation of lipids with ring structures. 2?-methylklavuzon suppressed phosphate-containing lipids significantly and decreased carbonyl containing lipids and cholesterol slightly. 2?-methylklavuzon caused increases in the hydrocarbon chain length. Overall, 2?-methylklavuzon can be used as a lipid-lowering compound in the treatment of NSCLC and other cancer therapies. © 2020 Elsevier B.V.
Citation - WoS: 11
Citation - Scopus: 14
3D Bioprinting of mouse pre-osteoblasts and human MSCs using bioinks consisting of gelatin and decellularized bone particles
(Iop Publishing Ltd, 2024) Kara, Aylin; Distler, Thomas; Akkineni, Ashwini Rahul; Tihminlioglu, Funda; Gelinsky, Michael; Boccaccini, Aldo R.
One of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix, preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone. Besides, there is a need to investigate the effects of decellularized bone (DB) particles as a tissue-based additive in bioink formulation to develop functional bioinks. Here we evaluated the effect of incorporating DB particles of different sizes (<= 45 and <= 100 mu m) and concentrations (1%, 5%, 10% (wt %)) into bioink formulations containing gelatin (GEL) and pre-osteoblasts (MC3T3-E1) or human mesenchymal stem cells (hTERT-MSCs). In addition, we propose a minimalistic bioink formulation using GEL, DB particles and cells with an easy preparation process resulting in a high cell viability. The printability properties of the inks were evaluated. Additionally, rheological properties were determined with shear thinning and thixotropy tests. The bioprinted constructs were cultured for 28 days. The viability, proliferation, and osteogenic differentiation capacity of cells were evaluated using biochemical assays and fluorescence microscopy. The incorporation of DB particles enhanced cell proliferation and osteogenic differentiation capacity which might be due to the natural collagen and hydroxyapatite content of DB particles. Alkaline phosphatase activity is increased significantly by using DB particles, notably, without an osteogenic induction of the cells. Moreover, fluorescence images display pronounced cell-material interaction and cell attachment inside the constructs. With these promising results, the present minimalistic bioink formulation is envisioned as a potential candidate for bone tissue engineering as a clinically translatable material with straightforward preparation and high cell activity.
Citation - WoS: 48
Citation - Scopus: 54
3d Printed Gelatin/Decellularized Bone Composite Scaffolds for Bone Tissue Engineering: Fabrication, Characterization and Cytocompatibility Study
(Elsevier, 2022-06) Kara, Aylin; Distler, Thomas; Polley, Christian; Schneidereit, Dominik; Seitz, Hermann; Friedrich, Oliver; Tıhmınlıoğlu, Funda; Boccaccini, Aldo R
Three-dimensional (3D) printing technology enables the design of personalized scaffolds with tunable pore size and composition. Combining decellularization and 3D printing techniques provides the opportunity to fabricate scaffolds with high potential to mimic native tissue. The aim of this study is to produce novel decellularized bone extracellular matrix (dbECM)-reinforced composite-scaffold that can be used as a biomaterial for bone tissue engineering. Decellularized bone particles (dbPTs, ∼100 μm diameter) were obtained from rabbit femur and used as a reinforcement agent by mixing with gelatin (GEL) in different concentrations. 3D scaffolds were fabricated by using an extrusion-based bioprinter and crosslinking with microbial transglutaminase (mTG) enzyme, followed by freeze-drying to obtain porous structures. Fabricated 3D scaffolds were characterized morphologically, mechanically, and chemically. Furthermore, MC3T3-E1 mouse pre-osteoblast cells were seeded on the dbPTs reinforced GEL scaffolds (GEL/dbPTs) and cultured for 21 days to assess cytocompatibility and cell attachment. We demonstrate the 3D-printability of dbPTs-reinforced GEL hydrogels and the achievement of homogenous distribution of the dbPTs in the whole scaffold structure, as well as bioactivity and cytocompatibility of GEL/dbPTs scaffolds. It was shown that Young's modulus and degradation rate of scaffolds were enhanced with increasing dbPTs content. Multiphoton microscopy imaging displayed the interaction of cells with dbPTs, indicating attachment and proliferation of cells around the particles as well as into the GEL-particle hydrogels. Our results demonstrate that GEL/dbPTs hydrogel formulations have potential for bone tissue engineering.
3d Printing-Assisted Fabrication of Microfluidic Pneumatic Valves
(IEEE, 2023) Keleş, Şeyda; Karakuzu, Betül; Tekin, Hüseyin Cumhur
Pneumatic valves have a crucial place in the fluidic control in microfluidic systems. Pneumatic valves containing polydimethylsiloxane (PDMS) membrane structures are used in microfluidic systems such as cell separation, and cell manipulation due to their flexible structure, and ease of production. This study demonstrates the rapid and straightforward fabrication of pneumatic valve structures using PDMS membranes, achieved through the utilization of 3D-printed molds. As a result of our experiments, we observed valve closure in a fluidic channel with a height of 150 μm. This closure was achieved by utilizing 400 μm × 800 μm PDMS membrane with a thickness of 66 μm positioned between the fluidic and control channels, while applying 1.5 bar of pressure to the control channel. When the pressure is removed, the opening time of the valve is only 0.02 s, and this response time allows rapid valving function. The presented valve fabrication strategy would allow easy and low-cost production of sophisticated microfluidic chips. © 2023 IEEE.
Citation - WoS: 7
Citation - Scopus: 9
Absorbance-Based Detection of Arsenic in a Microfluidic System With Push-And Pumping
(Elsevier, 2021) Karakuzu, Betül; Gülmez, Yekta; Tekin, H. Cumhur
Rapid and portable analysis of arsenic (As) contamination in drinking water is very important due to its adverse health effects on humans. Available commercial detection kits have shown low sensitivity and selectivity in analysis, and also they can generate harmful by-products. Microfluidic-based approaches allow portable analysis with gold nanoparticles (AuNPs) as labels. However, they need complex surface modification steps that complicate detection protocols. Due to the lack of precise sensing and affordable solution, we focused on developing a microfluidic platform that uses a push-and-pull pumping method for sensitive detection of As. In this detection principle, a sample is introduced in the microfluidic channel modified with -SH functional groups where As can bind. Then, AuNPs are given in the channel and AuNPs bind on free -SH functional groups which are not allocated with As. Absorbance measurements are conducted to detect AuNPs absorbed on the surfaces and the resulting absorbance value is inversely proportional with As concentration. The method enables detection of As down to 2.2 mu g/L concentration levels in drinking water, which is well-below the allowed maximum As concentration of 10 mu g/L in the drinking waters by the World Health Organization (WHO). The paper reveals that multiple push-and-pull pumping of fixed volume of sample and AuNPs with a syringe pump can improve the binding efficiency in the microfluidic channel. With this technique, low amounts of sample (1 mL) and short total assay time (25 min) are sufficient to detect As.
Citation - WoS: 3
Citation - Scopus: 3
Active Mixing Strategy With Electromechanical Platform for Lab-On Applications
(Institute of Electrical and Electronics Engineers Inc., 2019) Karakuzu, Betül; Özçivici, Engin; Tekin, Hüseyin Cumhur; Tarım, E. Alperay
The main purpose of this study is to present a new active mixing strategy that can be used for lab-on-A-chip applications to shorten analysis time. An electromechanical platform composed of stepper and DC motors is designed and manufactured. This platform allows rapid mixing in microwells of a polydimethylsiloxane chip for analysis. Mixing in microwells is performed with a stirring bar spun automatically using the electromechanical platform. Mixing experiments performed at different spinning speeds and different time intervals on the platform. It was observed that mixing was achieved only in 300 ms inside 100 ?L microwell using 4300 revolutions per minute (rpm) spinning speeds. Hence, the proposed mixing strategy showed 200-fold faster mixing than pure diffusion-based mixing. © 2019 IEEE.
Citation - WoS: 16
Citation - Scopus: 21
Adhesive Bonding Strategies To Fabricate High-Strength and Transparent 3d Printed Microfluidic Device
(American Institute of Physics, 2020) Keçili, Seren; Tekin, Hüseyin Cumhur
Recently, the use of 3D printing technologies has become prevalent in microfluidic applications. Although these technologies enable low-cost, rapid, and easy fabrication of microfluidic devices, fabricated devices suffer from optical opaqueness that inhibits their use for microscopic imaging. This study investigates bonding strategies using polydimethylsiloxane (PDMS) and printer resin as interlayer materials to fabricate high-strength optically transparent 3D-printed microfluidic devices. First, we fabricated microfluidic structures using a stereolithography 3D printer. We placed 3D-printed structures on interlayer materials coated surfaces. Then, we either let these 3D-printed structures rest on the coated slides or transferred them to new glass slides. We achieved bonding between 3D-printed structures and glass substrates with UV exposure for resin and with elevated temperature for PDMS interlayer materials. Bonding strength was investigated for different interlayer material thicknesses. We also analyzed the bright-field and fluorescence imaging capability of microfluidic devices fabricated using different bonding strategies. We achieve up to twofold (9.1 bar) improved bonding strength and comparable fluorescence sensitivity with respect to microfluidic devices fabricated using the traditional plasma activated PDMS-glass bonding method. Although stereolithography 3D printer allows fabrication of enclosed channels having dimensions down to similar to 600 mu m, monolithic transparent microfluidic channels with 280 x 110 mu m(2) cross section can be realized using adhesive interlayers. Furthermore, 3D-printed microfluidic chips can be integrated successfully with Protein-G modified substrates using resin interlayers for detection of fluorescent-labeled immunoglobulin down to similar to 30 ng/ml. Hence, this strategy can be applied to fabricate high-strength and transparent microfluidic chips for various optical imaging applications including biosensing.
Citation - WoS: 7
Citation - Scopus: 10
Adjuvant Potency of Astragaloside Vii Embedded Cholesterol Nanoparticles for H3n2 Influenza Vaccine
(TÜBİTAK, 2020) Genç, Rukan; Yakuboğulları, Nilgün; Nalbantsoy, Ayşe; Coven, Fethiye; Bedir, Erdal
Adjuvants are substances that increase the immune response to a given antigen. In the development of novel vaccine adjuvants/systems, saponins are one of the most attractive molecules due to their altered immunomodulatory activities. In this study, we tried to develop PEG (polyethylene glycol)/cholesterol-based lipid nanoparticles (LNPs) to deliver the Astragaloside VII (AST-VII) and potentiate adjuvant properties of AST-VII for the influenza vaccine. In the formation of PEG/cholesterol/AST-VII-based LNPs (PEG300: Chol-AST-VII LNPs), 3 different primary solvents (acetone, ethanol, and chloroform) were evaluated, employing their effects on hydrodynamic particle size, distribution, surface chemistry, and colloidal stability. Prepared nanoparticles were simply admixtured with inactivated influenza antigen (H3N2) and applied to PMA (phorbol 12-myristate 13-acetate)-ionomycin treated human whole blood to evaluate their cytokine release profile. PEG300: Chol-AST-VII LNPs (80.2 +/- 7.7 nm) were obtained using chloroform as a desolvation agent. Co-treatment of PMA-ionomycin with AST-VII and PEG300: Chol-AST-VII LNPs significantly increased the levels of IL-2 and IFN-gamma, compared to PMA-ionomycin alone. In the presence of H3N2, AST-VII was able to augment IL-17A, while PEG300: Chol-AST-VII LNPs stimulated the production of IFN-gamma. Hemolysis was only observed in PEG300: Chol-AST-VII LNPs (250 mu g/mL) treatment. AST-VII and AST-VII-integrated LNPs could be used as efficacious adjuvants for an inactivated H3N2 vaccine in vitro, and cytokine response through Th1/Th17 route was reported.
Citation - WoS: 4
Citation - Scopus: 5
Adsorption/Desorption and Biofunctional Properties of Oleuropein Loaded on Different Types of Silk Fibroin Matrices
(The Society of Chemists and Techonogists of Macedonia, 2017) Bayraktar, Oğuz; Balta, Ali Bora; Başal Bayraktar, Güldemet
The objective of this study was to investigate the adsorption/desorption behavior of oleuropein on different types of silk fibroin matrices including silk fibroin microfibers (MF), regenerated silk fibroin (RSF), and silk fibroin nanofibers (NF). Nanofibers with an average diameter of ranging between 24 and 326 nm were successfully prepared using the electrospinning technique. The effects of the silk fibroin concentration, the voltage applied and the distance between needle tip and collector plate on the morphol-ogy of the NF were investigated. The adsorption capacities of MF, RSF and NF were determined as 104.92, 163.07 and 228.34 mg oleuropein per gram of material, respectively. The percentage of initially adsorbed oleuropein that was desorbed was 86.08, 91.29 and 96.67% for MF, RSF and NF, respectively. NF and RSF discs loaded with oleuropein were subjected to disc diffusion assays to determine their antibacterial activity against test microorganisms Staphylococcus epidermidis (Gram +) and Esche-richia coli (Gram -). The results showed that both biomaterials possessed antibacterial properties after loading with oleuropein. Wound scratch assays using oleuropein released from NF revealed an enhance-ment of cell migration, indicating a wound healing property of the material. In conclusion, the NF can be utilized as a biofunctional polymeric material with better perfor-mance for the adsorption and desorption of oleuropein compared with MF and RSF.
Akt Inhibitor Arq 092 and Sorafenib Additively Inhibit Progression of Hepatocellular Carcinoma and Improve Immune System in Cirrhotic Rat Model
(Elsevier, 2017) Jilkova, Z. M.; Zeybek Kuyucu, Ayça; Kurma, K.; Pour, S. T. A.; Roth, G. S.; Abbadessa, G.; Decaens, T.
Background and Aims: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stages with limited number of therapeutic options. Longer exposure to classical treatment of advanced HCC, sorafenib, often over-activates AKT pathway, leading to HCC resistance. Moreover, AKT pathway itself is activated in almost half of HCC cases. Therefore, we investigated the efficacy of combination of Sorafenib with allosteric Akt inhibitor ARQ 092 in a DEN-induced cirrhotic rat model with HCC.
Anthraquinones and Macrocyclic Lactones From Endophytic Fungus Penicillium Roseopurpureum and Their Bioactivities
(ACG Publications, 2024) Dizmen,B.; Üner,G.; Küçüksolak,M.; Gören,A.C.; Kırmızıbayrak,P.B.; Bedir,E.
Endophytic fungi colonize the internal and distinct tissues of the host plants. In recent years, there has been growing interest in endophytic fungi as valuable sources for drug discovery based on their rich metabolic profiles consisting of novel and bioactive compounds. Accordingly, our preliminary study demonstrated that an endophyte, namely Penicillium roseopurpureum isolated from Astragalus angustifolius, had high chemical diversity with an antiproliferative effect. Herein, fermentation of P. roseopurpureum resulted in the production of five new anthraquinone-type compounds (2, 4, 6, 7, 8) together with several known compounds [11-methoxycurvularin (1: epimeric mixture of 1a and 1b), carviolin (3), 11-hydroxycurvularin (5: diastereoisomeric mixture of 5a and 5b) and 1-O-methylemodin (9)]. The structures of the new compounds were established by NMR spectroscopy and HR-MS analysis. Cytotoxicity studies demonstrated that none of the compounds except for 1 and 5 had antiproliferative activity against prostate cancer cell lines. Interestingly, 1 was found as cytotoxic, whereas 5 exhibited cytostatic properties. Also, 7-AAD/Annexin V staining supported these results by showing that 1 caused cellular death, while 5 did not show any increase in dead cell content in comparison to the control. Lastly, cell cycle analysis showed that compounds had distinctive cell cycle arrest patterns. © 2024 ACG Publications.
Citation - WoS: 3
Citation - Scopus: 5
Antioxidant and Antimicrobial Activities of Plants Grown in the Mediterranean Region
(John Wiley and Sons Inc., 2022) Kaçar, D.; Bayraktar, Oğuz; Erdem, C.; Alamri, A.S.; Galanakis, C.M.
Background: The main objective of this research was to identify plant species with possible bioactivities based on their total phenol content, antioxidant, and antimicrobial properties. Therefore, different parts of 42 plant species grown in the Mediterranean region were extracted with aqueous ethanol solutions to prepare extracts with antioxidant and antimicrobial activities, mainly resulting from their total phenol contents. No detailed laboratory data on the flora of this area exists regarding their total phenol contents and total antioxidant activities. Results: Yields of extraction for each plant material were determined. Extracts were characterized based on their total phenol contents, total antioxidant (both hydrophilic and lipophilic), and antimicrobial activities using Folin–Ciocalteu, Photochemiluminescence, disc diffusion, and microdilution methods, respectively. The extract of Hypericum empetrifolium had the relatively highest total water-soluble and lipid-soluble antioxidant activities. Sarcopoterium spinosum extract had relatively high total phenol content. Preliminary screening study was conducted with the disc diffusion method to evaluate the extracts' antimicrobial activities. 26 out of 42 plant species showed significant antimicrobial activities against the growth of microorganisms. Microdilution assays were performed to evaluate the most active plant species with their minimum inhibition concentrations. H. empetrifolium, Pistacia terebinthus, Arbutus unedo, and Cistus parviflorus were the most antimicrobial plant species among those investigated. CONCLUSION: The new potential sources for the isolation of bioactive natural compounds from specific plant species could be possible with the help of this present screening study. Isolated bioactive natural compounds can be utilized as raw materials in cosmetics, nutraceuticals, food supplements, and pharmaceutical industries. © 2022 Society of Chemical Industry.
Citation - WoS: 4
Antioxidant, Antimicrobial and Cytotoxic Activities of Extracts From Some Selected Mediterranean Shrub Species (maquis)
(Biointerface Research Applied Chemistry, 2016) Bayraktar, Oğuz; Altıok, Evren; Yılmazer, Özgür; Rusçuklu, Dane; Büyüköz, Melda
In this study in vitro antioxidant, antimicrobial and cytotoxic activities of ethanol extracts of some plants from Urla region in Turkey were investigated. Plant material samples of Pistacia lentiscus, Vitex agnus-castus, Cistus creticus and Nerium oleander were collected in October, November and December. The harvesting time significantly affected their antioxidant, antimicrobial and cytotoxic activities of these plant extracts. The highest biological activities in terms of antioxidant, antimicrobial and cytotoxic activities were observed for the leaf extract of C. creticus. The applied doses of leaf extracts of C. creticus, P. lentiscus, and N. oleander resulted in higher Bax and GAPDH expressions than those for control cells. These plant extracts may trigger apoptosis and may be a promising natural source for prostate cancer treatment.
Citation - WoS: 16
Citation - Scopus: 17
Antiproliferative Activity of (r)-4 '-methylklavuzon on Hepatocellular Carcinoma Cells and Epcam(+)/Cd133(+) Cancer Stem Cells Via Sirt1 and Exportin-1 (crm1) Inhibition
(Elsevier Ltd., 2019-10) Delman, Murat; Avcı, Sanem Tercan; Akçok, İsmail; Kanbur, Tuğçe; Erdal, Esra; Çağır, Ali
Cytotoxic effects of (R)-4'-methylklavuzon were investigated on hepatocellular carcinoma cells (HuH-7 and HepG2) and HuH-7 EpCAM(+)/CD133(+) cancer stem cells. IC50 of (R)-4'-methylklavuzon was found as 1.25 mu M for HuH-7 parental cells while it was found as 2.50 mu M for HuH-7 EpCAM(+)/CD133(+) cancer stem cells. (R)-4'-methylklavuzon tended to show more efficient in vitro cytotoxicity with its lower IC50 values on hepatocellular carcinoma cell lines compared to its lead molecule, goniothalamin and FDA-approved drugs, sorafenib and regorafenib. Cell-based Sirtuin/HDAC enzyme activity measurements revealed that endogenous Sirtuin/HDAC enzymes were reduced by 40% compared to control. SIRT1 protein levels were upregulated indicating triggered DNA repair mechanism. p53 was overexpressed in HepG2 cells. (R)-4'methylklavuzon inhibited CRM1 protein providing increased retention of p53 and RIOK2 protein in the nucleus. HuH-7 parental and EpCAM(+)/CD133(+) cancer stem cell spheroids lost intact morphology. 3D HepG2 spheroid viabilities were decreased in a correlation with upregulation in p53 protein levels. (C) 2019 Elsevier Masson SAS. All rights reserved.
Citation - WoS: 17
Citation - Scopus: 15
Antiproliferative 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, Gülşah
Alginate 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.
Citation - WoS: 3
Citation - Scopus: 4
Applicability of Low-Intensity Vibrations as a Regulatory Factor on Stem and Progenitor Cell Populations
(Bentham Science Publishers, 2020) Baskan, Öznur; Karadaş, Özge; Meşe, Gülistan; Özçivici, Engin
Persistent and transient mechanical loads can act as biological signals on all levels of an organism. It is therefore not surprising that most cell types can sense and respond to mechanical loads, similar to their interaction with biochemical and electrical signals. The presence or absence of mechanical forces can be an important determinant of form, function and health of many tissue types. Along with naturally occurring mechanical loads, it is possible to manipulate and apply external physical loads on tissues in biomedical sciences, either for prevention or treatment of catabolism related to many factors, including aging, paralysis, sedentary lifestyles and spaceflight. Mechanical loads consist of many components in their applied signal form such as magnitude, frequency, duration and intervals. Even though high magnitude mechanical loads with low frequencies (e.g. running or weight lifting) induce anabolism in musculoskeletal tissues, their applicability as anabolic agents is limited because of the required compliance and physical health of the target population. On the other hand, it is possible to use low magnitude and high frequency (e.g. in a vibratory form) mechanical loads for anabolism as well. Cells, including stem cells of the musculoskeletal tissue, are sensitive to high frequency, low-intensity mechanical signals. This sensitivity can be utilized not only for the targeted treatment of tissues, but also for stem cell expansion, differentiation and biomaterial interaction in tissue engineering applications. In this review, we reported recent advances in the application of low-intensity vibrations on stem and progenitor cell populations. Modulation of cellular behavior with low-intensity vibrations as an alternative or complementary factor to biochemical and scaffold induced signals may represent an increase of capabilities in studies related to tissue engineering.
Citation - WoS: 8
Citation - Scopus: 11
Application of Low Intensity Mechanical Vibrations for Bone Tissue Maintenance and Regeneration
(TÜBİTAK, 2016) Ölçüm, Melis; Baskan, Öznur; Karadaş, Özge; Özçivici, Engin
Physical exercise is beneficial for bone tissue health, yet its usage is limited for preventing osteoporosis. Even though natural for the bone tissue from development to homeostasis, mechanical loads present with a multitude of physical parameters, including amplitude, duration, frequency, and distribution. Utilizing the most beneficial parameters of mechanical loads may potentiate a nonpharmaceutical tool for biotechnology to prevent and treat bone loss related to aging, bedrest, sedentary lifestyles, weightlessness, and other diseases. Low intensity vibrations (LIVs) consist of mechanical loads with amplitudes smaller than loads prescribed by habitual activity, with a higher frequency. In this review, literature covering LIV signal application on bone tissue and cellular and molecular level is presented. Studies indicate that LIV signals are safe, anabolic, and anticatabolic for skeletal tissue and are of great significance in regenerative medicine applications.
Citation - WoS: 4
Citation - Scopus: 5
Application of Magnetic Levitation Induced Weightlessness To Detect Cell Lineage
(IEEE, 2019) Sarıgil, Öykü; Anıl İnevi, Müge; Yılmaz, Esra; Çağan, Melike; Meşe, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, Engin
Identification and classification of bone marrow cells is an important step for molecular biology and therapeutic studies related to bone marrow disorders such as osteoporosis or obesity. In this study, we applied magnetic levitation technology to induce a weightlessness environment to detect adipocytes and osteoblasts based on their single cell density. This biotechnological method can be used for separation of heterogeneous populations such as bone marrow once adapted to a continuous microfluidic platform.
Citation - WoS: 5
Citation - Scopus: 7
Ascorbic Acid Enhances the Metabolic Activity, Growth and Collagen Production of Human Dermal Fibroblasts Growing in Three-Dimensional (3D) Culture
(Gazi Üniversitesi, 2023) Dikici, Serkan
Tissue engineering (TE) enables the development of functional synthetic substitutes to be replaced with damaged tissues and organs instead of the use of auto or allografts. A wide range of biomaterials is currently in use as TE scaffolds. Among these materials, naturally sourced ones are favorable due to being highly biocompatible and supporting cell growth and function, whereas synthetic ones are advantageous because of the high tunability on mechanical and physical properties as well as being easy to process. Alongside the advantages of synthetic polymers, they mostly show hydrophobic behavior that limits biomaterial-cell interaction and, consequently, the functioning of the developed TE constructs. In this study, we assessed the impact of L-Ascorbic acid 2-phosphate (AA2P) on improving the culture conditions of human dermal fibroblasts (HDFs) growing on a three-dimensional (3D) scaffold made of polycaprolactone (PCL) using emulsion templating. Our results demonstrated that AA2P enhances the metabolic activity and growth of HDFs as well as collagen deposition by them when supplemented in their growth medium at 50 µg/mL concentration. It showed a great potential to be used as a growth medium supplement to circumvent the disadvantages of culturing human cells on a synthetic biomaterial that is not favored in default. AA2P's potential to improve cell growth and collagen deposition may prove an effective way to culture human cells on 3D PCL PolyHIPE scaffolds for various TE applications.
Assessment of Cell Cycle and Viability of Magnetic Levitation Assembled Cellular Structures
(IEEE, 2020) Anıl İnevi, Müge; Ünal, Yağmur Ceren; Yaman, Sena; Tekin, H. Cumhur; Meşe, Gülistan; Meşe, Gülistan
Label-free magnetic levitation is one of the most recent Earth-based in vitro techniques that simulate the microgravity. This technique offers a great opportunity to biofabricate scaffold-free 3-dimensional (3D) structures and to study the effects of microgravity on these structures. In this study, self-assembled 3D living structures were fabricated in a paramagnetic medium by magnetic levitation technique and effects of the technique on cellular health was assessed. This magnetic force-assisted assembly system applied here offers broad applications in several fields, such as space biotechnology and bottom-up tissue engineering.

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