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.Conference 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.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.Article Citation - WoS: 17Citation - Scopus: 22Protein Corona Formation on Silver Nanoparticles Under Different Conditions(Elsevier, 2022) Tomak, Aysel; Yılancıoğlu, Buket; Winkler, David; Öksel Karakuş, CeydaThe surfaces of nanoparticles become covered by biomolecules in biological fluids. This protein ‘corona’ modifies materials’ characteristics and biological activity. The composition of the protein corona is dynamic, abundant biomolecules that bind first are subsequently replaced by less abundant but more tightly bound ones. Here, we explore the formation of the silver nanoparticle protein corona on exposure to cell culture media containing 10 % fetal bovine serum supplemented Dulbecco's Modified Eagle's medium. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry analysis were used to monitor how different parameters such as incubation time, heating duration, cell culture medium, incubation temperature, and the number of washes affect the nanoparticle–protein corona complex. silver nanoparticles with and without bound proteins were characterized by electron microscopy, dynamic light scattering, and ultraviolet-visible-near-IR spectroscopy. The tetrazolium-based MTT assay was used to determine viability of A549 human lung adenocarcinoma cells treated with silver nanoparticles. Characterization of the nanoparticles before and after protein binding provided insights into their changing morphology on corona formation. Our results confirmed that the physiological environment directly affects protein corona formation on nanoparticle surfaces. In particular, incubation condition-dependent differences in the amount of bound proteins were observed. This work highlights the importance of environmental drivers of protein adsorption, which should be considered when predicting and/or controlling protein targets of silver nanoparticles.Article Citation - WoS: 69Citation - Scopus: 73Nanoparticle-Protein Corona Complex: Understanding Multiple Interactions Between Environmental Factors, Corona Formation, and Biological Activity(Taylor & Francis, 2021) Öksel Karakuş, Ceyda; Tomak, Aysel; Çeşmeli, Selin; Hanoğlu, Berçem Dilan; Winkler, DavidThe surfaces of pristine nanoparticles become rapidly coated by proteins in biological fluids, forming the so-called protein corona. The corona modifies key physicochemical characteristics of nanoparticle surfaces that modulate its biological and pharmacokinetic activity, biodistribution, and safety. In the two decades since the protein corona was identified, the importance of nano particles surface properties in regulating biological responses have been recognized. However, there is still a lack of clarity about the relationships between physiological conditions and cor ona composition over time, and how this controls biological activities/interactions. Here we review recent progress in characterizing the structure and composition of protein corona as a function of biological fluid and time. We summarize the influence of nanoparticle characteristics on protein corona composition and discuss the relevance of protein corona to the biological activity and fate of nanoparticles. The aim is to provide a critical summary of the key factors that affect protein corona formation (e.g. characteristics of nanoparticles and biological environ ment) and how the corona modulates biological activity, cellular uptake, biodistribution, and drug delivery. In addition to a discussion on the importance of the characterization of protein corona adsorbed on nanoparticle surfaces under conditions that mimic relevant physiological environment, we discuss the unresolved technical issues related to the characterization of nano particle-protein corona complexes during their journey in the body. Lastly, the paper offers a perspective on how the existing nanomaterial toxicity data obtained from in vitro studies should be reconsidered in the light of the presence of a protein corona, and how recent advances in fields, such as proteomics and machine learning can be integrated into the quantitative analysis of protein corona components.Article Citation - WoS: 10Citation - Scopus: 13Overcoming Roadblocks in Computational Roadmaps To the Future for Safe Nanotechnology(IOP Publishing, 2021) Öksel Karakuş, Ceyda; Winkler, David A.The rapid rise of nanotechnology has resulted in a parallel rise in the number of products containing nanomaterials. The unusual properties that nano forms of materials exhibit relative to the bulk has driven intense research interest and relatively rapid adoption by industry. Regulatory agencies are charged with protecting workers, the public, and the environment from any adverse effects of nanomaterials that may also arise because of these novel physical and chemical properties. They need data and models that allow them to flag nanomaterials that may be of concern, while balancing potential stifling of commercial innovation. Roadmaps for the future of safe nanotechnology were defined more than a decade ago, but many roadblocks identified in these studies remain. Here, we discuss the roadblocks that are still hindering the effective application of informatics and predictive computational nanotoxicology methods from providing more effective guidance to nanomaterials regulatory agencies and safe-by-design rationale for industry. We describe how developments in high throughput synthesis, characterization, and biological assessment of nanomaterials will overcome many of these roadblocks, allowing a clearly defined roadmap for computational design of effective but safe-by-design nanomaterials to be realized.