Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 13Citation - Scopus: 17Machine Learning-Assisted Prediction of the Toxicity of Silver Nanoparticles: a Meta-Analysis(Springer, 2023) Bilgi, Eyüp; Öksel Karakuş, CeydaSilver nanoparticles are likely to be more dangerous than other forms of silver due to the intracellular release of silver ions upon dissolution and the formation of mixed ion-containing complexes. Such concerns have resulted in an ever-growing pile of scientific evaluations addressing the safety aspects of nanosilver with widely varying methodological approaches. The substantial differences in the conduct/design of nanotoxicity screening have led to the generation of conflicting findings that may be accurate in their narrative but fail to provide a complete picture. One strategy to maximize the use of individual risk assessments with potentially biased estimates of toxicological effects is to homogenize results across several studies and to increase the generalizability and human relevance of their findings. Here, we collected a large pool of data (n=162 independent studies) on the cytotoxicity of nanosilver and unrevealed potential triggers of toxicity. Two different machine learning approaches, decision tree (DT) and artificial neural network (ANN), were primarily employed to develop models that can predict the cytotoxic potential of nanosilver based on material- and assay-related parameters. Other machine learning algorithms (logistic regression, Gaussian Naive Bayes, k-nearest neighbor, and random forest classifiers) were also applied. Among several attributes compared, exposure concentration, duration, zeta potential, particle size, and coating were found to have the most substantial impact on nanotoxicity, with biomolecule- and microorganism-assisted surface modifications having the most beneficial and detrimental effects on cell survival, respectively. Such machine learning-assisted efforts are critical to developing commercially viable and safe nanosilver-containing products in the ever-expanding nanobiomaterial market.Article Modelling Genotoxic Effects of Metal Oxide Nanoparticles Using Qsar Approach(2022) Öksel Karakuş, CeydaWe investigated the application of structure-activity relationship approaches to underpin structural properties that potentially control the genotoxic potential of 9 different metal oxide nanoparticles (CuO, ZnO, NiO, SiO2, TiO2, CeO2, Fe2O3, Fe3O4 and Co3O4). In particular, we compiled a pool of quantum-mechanical, experimental and periodic table-driven descriptors and explored their distinctive contribution to the measured activity (genotoxicity). We first employed a clustered heatmap and parallel coordinates plot for visual exploration of the clusters and outliers of the data and finding corresponding responsible physicochemical descriptors. We then investigated the strength (and direction) of the relationship among descriptors and between descriptors and genotoxicity using similarity metrics. By using orthogonal projections to latent structures (OPLS), we were able to quantify the relative contribution of each descriptor to the genotoxicity of metal oxide nanoparticles. Our results suggested that zeta potential, the ratio of core electrons to valence electrons, Fermi energy and electronegativity were significant predictors of genotoxicity. Such computer-assisted approaches hold considerable promise for maximizing the use of accumulated data in nanotoxicology, prioritizing nanoparticles for further testing and filling data gaps required for hazard assessment processes.Article Citation - WoS: 4Citation - Scopus: 4Optimizing the Dispersion of Calcium Phosphate Nanoparticles for Cellular Studies Using Statistical Design of Experiments(Elsevier, 2023) Önder, Anıl Can; Tomak, Aysel; Öksel Karakuş, CeydaThe in vitro experimentation of ceramic nanoparticles often requires their dispersion in liquid media without causing particle clumps or deteriorating sample integrity. However, the dispersion of nanoparticles using the available protocols rarely leads to stable and uniform dispersions which, in turn, raises concerns about the validity, repeatability and comparability of the findings observed in vitro. Moreover, the ability to control the final dispersion quality of ceramic nanoparticles is an essential step to obtaining optimized nanoceramic materials with desired functionality and to enhancing their performance in subsequent applications. While the need to have a comprehensive guideline for the dispersion of nanoparticles has led to several published documents and protocols, the dispersion methodology of ceramic nanoparticles and the relative contribution of the experimental parameters to the quality of resulting dispersion are still not clear. Here, we employed the statistical design of experiment (DoE) approach to systematically assess the magnitude and source of variation in dispersion quality of two different ceramic nanoparticles, hydroxyapatite and tricalcium phosphate. Using the first-order Plackett-Burman Design (PBD), nanoparticle concentration, pH and the presence of an additive were identified as the most critical factors influencing the resulting hydrodynamic size and zeta potential of the ceramic nanoparticles. Optimization using a second-order Central Composite Design (CCD) yielded a set of quadratic regression equations that were used to predict the hydrodynamic size or zeta potential of ceramic nanoparticles with high accuracy (R2, 0.88–0.92). The results of PBD screening and CCD optimization experiments were employed to prepare nanoparticle dispersions of different quality, which were then used to compare the effect of aggregation on the viability of human osteosarcoma (SaOS-2) cells. Overall, the results of this study provided insight into the role that various experimental parameters play in the colloidal stability and dispersion of ceramic nanoparticles. © 2023Conference Object Investigation of the Cytotoxicity of Bioceramic Nanoparticles on Saos-2 Cells by an Alternative Method(Elsevier Ireland Ltd, 2022) Tomak, Aysel; Önder, A. C.; Öksel Karakuş, CeydaReview 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: 1Citation - Scopus: 1Exploring the Heterogeneity of Ige-Mediated Food Allergy Through Latent Class Analysis(S. Karger AG, 2022) Akarsu, Ayşegül; Öksel Karakuş, Ceyda; Ocak, Melike; Oral, Nihan; Bilgi, Eyüp; Şahiner, Ümit Murat; Soyer, Özge; Şekerel, Bülent EnisIntroduction: Food allergy (FA) is a heterogeneous disease with multiple morbidities and a huge burden for patients and healthcare systems. Variable manifestations, comorbidities (atopic dermatitis [AD], asthma, and/or allergic rhinitis [AR]), severity (anaphylaxis), and outcomes suggest the existence of different endotypes that cluster analyses may reveal. In this study, we aimed to investigate distinct subgroups among patients with FAs using data from 524 children/adolescents. Methods: 524 patients with IgE-mediated FA (353 male [67%]; median age 4.4 years [IQR:3.0-6.8]), 354 (68%) had multiple FA. The history of AD, asthma, AR, and anaphylaxis was recorded in 59.4%, 35.5%, 24.2%, and 51.2% of the patients, respectively. Latent class analysis was carried out to distinguish clinical FA phenotypes using five potential markers of allergy severity (single/multiple FA, never/inactive/current asthma and AD, AR, and anaphylaxis). Results: Three distinct phenotypes were identified: (1) multiple FA with eczema and respiratory multimorbidity (42%), (2) multiple FA with persistent eczema (34%), and (3) single FA with respiratory multimorbidity without eczema (24%). Compared with the single FA cluster, the prevalence of AD was significantly higher in multiple FA groups. Cluster 1 had the highest frequency of AR and allergic asthma, and the lowest rate of total tolerance of FA. Discussion: We put forward the hypothesis of underlying pathogenesis according to the clinical phenotypes. While skin barrier defect may play a dominant role in the pathogenesis in Cluster 2, immune dysregulation may be dominant in Cluster 3. In Cluster 1, the most severe group, a combination of both skin barrier defects and immune dysregulation may be responsible for the clinical features.Conference Object Computational Nanotoxicology: a Case Study With Silver and Zinc Nanomaterials(Elsevier, 2022) Bilgi, Eyüp; Öksel Karakuş, CeydaNanomaterials (NMs) have been the focus of basic and applied research for more than two decades. According to the updated consumer materials inventory, over 1800 commercial NMs have taken their place in the market, 42% of which are in health and wellness category1. The widespread use of NMs in health-related products made not only the human exposure to the (residues of) NMs inevitable but also the long-recognized concerns over their safety a priority. Despite this pressing need, more than 70% of commercially available nano-containing products do not include sufficient information about their physicochemical and/or toxicological characteristics.Conference Object Citation - WoS: 1Green Synthesis of Nanostructured Bioactive Glass for Dental Applications(Elsevier, 2022) Tüncer, Melisa; Yücesoy, Deniz Tanıl; Öksel Karakuş, CeydaCalcium sodium phosphosilicate (known as bioactive glass) is a biomaterial commonly used in dental care products and bone tissue engineering applications due to biocompatibility, bone-forming and dentin sensitivity reduction capability. Bioactive 45S5 glass, so-called NovaMin, comprises of 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5 (wt%). It is traditionally synthesized by wet chemical methods such as melt-quenching and sol-gel which requires high temperature heating and the use of a strong acid catalyst, which brings into the question of the possibility of introducing toxic acid residues into the final product. Therefore, there is a clear need to develop environmental-friendly bioactive glass synthesis methods or to modify existing ones in a way to uplift their environmental friendliness.Conference Object Comparative Study of the Cytotoxicity of Hydroxyapatite, Tricalcium Phosphate and Calcium Phosphate Nanomaterials on Panc-1 and Hek293 Cell Line(Elsevier, 2022) Çeşmeli, Selin; Öksel Karakuş, CeydaCalcium phosphate-based bioceramic nanoparticles have been actively used in a range of therapeutic applications. Although they are mostly considered as biocompatible materials, the circulation of nanoparticles in the bloodstream raise further questions as to what degree of cellular damage they are capable of causing once carried out to vital organs such as kidney and pancreas. Therefore, there is a clear need to explore potential cellular damage induced by commercially used bioceramic nanoparticles such as hydroxyapatite (HAp), tricalcium phosphate (TCP) and calcium phosphate (CaP).Conference Object Development of Novel Nanotoxicity Assessment Method Utilizing 3d Printing System(Elsevier, 2022) Başlar, Muhammet Semih; Öksel Karakuş, Ceyda; Aldemir Dikici, BetülUnique 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.