Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 14Citation - Scopus: 163D 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.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: 6Citation - Scopus: 5Basidiomycota Species in Drosophila Gut Are Associated With Host Fat Metabolism(Nature Research, 2023) Bozkurt, Berkay; Terlemez, Gamze; Sezgin, EfeThe importance of bacterial microbiota on host metabolism and obesity risk is well documented. However, the role of fungal microbiota on host storage metabolite pools is largely unexplored. We aimed to investigate the role of microbiota on D. melanogaster fat metabolism, and examine interrelatedness between fungal and bacterial microbiota, and major metabolic pools. Fungal and bacterial microbiota profiles, fat, glycogen, and trehalose metabolic pools are measured in a context of genetic variation represented by whole genome sequenced inbred Drosophila Genetic Reference Panel (DGRP) samples. Increasing Basidiomycota, Acetobacter persici, Acetobacter pomorum, and Lactobacillus brevis levels correlated with decreasing triglyceride levels. Host genes and biological pathways, identified via genome-wide scans, associated with Basidiomycota and triglyceride levels were different suggesting the effect of Basidiomycota on fat metabolism is independent of host biological pathways that control fungal microbiota or host fat metabolism. Although triglyceride, glycogen and trehalose levels were highly correlated, microorganisms’ effect on triglyceride pool were independent of glycogen and trehalose levels. Multivariate analyses suggested positive interactions between Basidiomycota, A. persici, and L. brevis that collectively correlated negatively with fat and glycogen pools. In conclusion, fungal microbiota can be a major player in host fat metabolism. Interactions between fungal and bacterial microbiota may exert substantial control over host storage metabolite pools and influence obesity risk. © 2023, Springer Nature Limited.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.Article Citation - WoS: 7Citation - Scopus: 8Bioinspired Multi-Layer Biopolymer-Based Dental Implant Coating for Enhanced Osseointegration(Wiley, 2023) Üzülmez, Betül; Demirsoy, Zeynep; Can, Özge; Gülseren, GulcihanThe major drawbacks of metal-based implants are weak osseointegration and post-operational infections. These limitations restrict the long-term use of implants that may cause severe tissue damage and replacement of the implant. Recent strategies to enhance the osseointegration process require an elaborate fabrication process and suffer from post-operative complications. To address the current challenges taking inspiration from the extracellular matrix (ECM), the current study is designed to establish enhanced osseointegration with lowered risk of infection. Natural biopolymer pectin, peptide amphiphiles, and enzyme-mimicking fullerene moieties are governed to present an ECM-like environment around the implant surfaces. This multifunctional approach promotes osseointegration via inducing biomineralization and osteoblast differentiation. Application of the biopolymer-based composite to the metal surfaces significantly enhances cellular attachment, supports the mineral deposition, and upregulates osteoblast-specific gene expression. In addition to the osteoinductive properties of the constructed layers, the inherent antimicrobial properties of multilayer coating are also used to prevent infection possibility. The reported biopolymer-artificial enzyme composite demonstrates antimicrobial activity against Escherichia coli and Bacillus subtilis as a multifunctional surface coating.Article Citation - WoS: 7Citation - Scopus: 7Potent Telomerase Activators From a Novel Sapogenin Via Biotransformation Utilizing Camarosporium Laburnicola, an Endophytic Fungus(BioMed Central Ltd., 2023) Küçüksolak, Melis; Yılmaz, Sinem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalBACKGROUND: Cycloartane-type triterpenoids possess important biological activities, including immunostimulant, wound healing, and telomerase activation. Biotransformation is one of the derivatization strategies of natural products to improve their bioactivities. Endophytic fungi have attracted attention in biotransformation studies because of their ability to perform modifications in complex structures with a high degree of stereospecificity. RESULTS: This study focuses on biotransformation studies on cyclocephagenol (1), a novel cycloartane-type sapogenin from Astragalus species, and its 12-hydroxy derivatives (2 and 3) to obtain new telomerase activators. Since the hTERT protein levels of cyclocephagenol (1) and its 12-hydroxy derivatives (2 and 3) on HEKn cells were found to be notable, biotransformation studies were carried out on cyclocephagenol and its 12-hydroxy derivatives using Camarosporium laburnicola, an endophytic fungus isolated from Astragalus angustifolius. Later, immunoblotting and PCR-based ELISA assay were used to screen starting compounds and biotransformation products for their effects on hTERT protein levels and telomerase activation. All compounds showed improved telomerase activation compared to the control group. CONCLUSIONS: As a result of biotransformation studies, seven new metabolites were obtained and characterized, verifying the potential of C. laburnicola as a biocatalyst. Additionally, the bioactivity results showed that this endophytic biocatalyst is unique in transforming the metabolites of its host to afford potent telomerase activators. © 2023. The Author(s).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.Review Citation - WoS: 23Citation - Scopus: 24Microfluidic-Based Technologies for Diagnosis, Prevention, and Treatment of Covid-19: Recent Advances and Future Directions(Springer, 2023) Tarım, Ergün Alperay; Anıl İnevi, Müge; Özkan, İlayda; Keçili, Seren; Bilgi, Eyüp; Başlar, Muhammet Semih; Özçivici, Engin; Öksel Karakuş, Ceyda; Tekin, Hüseyin CumhurThe COVID-19 pandemic has posed significant challenges to existing healthcare systems around the world. The urgent need for the development of diagnostic and therapeutic strategies for COVID-19 has boomed the demand for new technologies that can improve current healthcare approaches, moving towards more advanced, digitalized, personalized, and patient-oriented systems. Microfluidic-based technologies involve the miniaturization of large-scale devices and laboratory-based procedures, enabling complex chemical and biological operations that are conventionally performed at the macro-scale to be carried out on the microscale or less. The advantages microfluidic systems offer such as rapid, low-cost, accurate, and on-site solutions make these tools extremely useful and effective in the fight against COVID-19. In particular, microfluidic-assisted systems are of great interest in different COVID-19-related domains, varying from direct and indirect detection of COVID-19 infections to drug and vaccine discovery and their targeted delivery. Here, we review recent advances in the use of microfluidic platforms to diagnose, treat or prevent COVID-19. We start by summarizing recent microfluidic-based diagnostic solutions applicable to COVID-19. We then highlight the key roles microfluidics play in developing COVID-19 vaccines and testing how vaccine candidates perform, with a focus on RNA-delivery technologies and nano-carriers. Next, microfluidic-based efforts devoted to assessing the efficacy of potential COVID-19 drugs, either repurposed or new, and their targeted delivery to infected sites are summarized. We conclude by providing future perspectives and research directions that are critical to effectively prevent or respond to future pandemics.Article Citation - WoS: 6Citation - Scopus: 6Diagnosis of Ruminant Viral Diseases With Loop-Mediated Isothermal Amplification(Springer, 2023) Ayaz Kök, Sanem; Üstün, Selcen; Taşkent, HümeyraInfectious diseases in livestock industry are major problems for animal health, food safety, and the economy. Zoonotic diseases from farm animals are significant threat to human population as well. These are notifiable diseases listed by the World Organization for Animal Health (OIE). Rapid diagnostic methods can help keep infectious diseases under control in herds. Loop-mediated isothermal amplification (LAMP) is a simple and rapid nucleic acid amplification method that is studied widely for detection of many infectious diseases in the field. LAMP allows biosensing of target DNA or RNA under isothermal conditions with high specificity in a short period of time. An untrained user can analyze results based on color change or turbidity. Here we review LAMP assays to diagnose OIE notifiable ruminant viral diseases in literature highlighting properties of LAMP method considering what is expected from an efficient, field usable diagnostic test.