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Öğe Bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic or artificial cavitation nuclei(Elsevier Science Inc, 2021) Edsall, Connor; Khan, Zerin Mahzabin; Mancia, Lauren; Hall, Sarah; Mustafa, Waleed; Johnsen, Eric; Klibanov, Alexander L.; Yüksel Durmaz, Yasemin; Vlaisavljevich, EliThe study described here examined the effects of cavitation nuclei characteristics on histotripsy. Highspeed optical imaging was used to compare bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic and artificial cavitation nuclei (gas-filled microbubbles, fluid-filled nanocones). Results showed a significant decrease in the cavitation threshold for microbubbles and nanocones compared with intrinsic-nuclei controls, with predictable and well-defined bubble clouds generated in all cases. Red blood cell experiments showed complete ablations for intrinsic and nanocone phantoms, but only partial ablation in microbubble phantoms. Results also revealed a lower rate of ablation in artificial-nuclei phantoms because of reduced bubble expansion (and corresponding decreases in stress and strain). Overall, this study demonstrates the potential of using artificial nuclei to reduce the histotripsy cavitation threshold while highlighting differences in the bubble cloud behavior and ablation capacity that need to be considered in the future development of these approaches.Öğe Experimental and computational investigation of clustering behavior of cyclodextrin-perfluorocarbon inclusion complexes as effective histotripsy agents(American Chemical Society, 2022) Kaymaz, Betül; Mustafa, Waleed; Hall, Sarah; Vlaisavljevich, Eli; Şensoy, Özge; Yüksel Durmaz, YaseminRecently developed nanocones (NCs), which are inclusion complexes that are made up of cyclodextrins (CDs) and perfluorocarbons (PFCs), have shown promising results in nanoparticle-mediated histotripsy (NMH) applications due to stable inclusion complexation, PFC quantification, simple synthesis, and processing. FDA-approved ?CD and its modified versions such as low-degree methylated ?CD have been previously demonstrated as prime examples of structures capable of accommodating PFC molecules. However, the complex formation potential of different CDs with various cavity sizes in the presence of PFC molecules, and their consequent aggregation, needs to be explored. In the present study, the complexation and aggregation potential of some natural CDs and their respective derivatives either exposed to perfluoropentane (PFP) or perfluorohexane (PFH) were studied in the wet lab. Computational studies were also performed to account for the limitations faced in PFC quantification because of the low optical density of PFCs within the CD complex and to discover the best candidate for NMH applications. All results revealed that only ?CD and ?CD (except HM?CD) derivatives form an inclusion complex with PFCs and only LM?CD, ?CD, and ?CD form nanocone clusters (NCCs), which precipitate and can be collected for use. Furthermore, the data collectively show that ?CD and PFCs have the best complexation due to stable complex formation, ease of production, and product recovery, especially with PFH as a more suitable candidate due to its high boiling point, which allows workability during synthesis. Although simulations suggest that highly stable inclusion complexes exist, such as HP?CD, the cluster formation resulting in precipitation is hindered due to the high solubility of CDs in water, resulting in intangible yields to work with even after employing general laboratory recovery methods. Conclusively, histotripsy cavitation experiments successfully showed a decreased cavitation threshold among optimal NCC candidates that were identified, supporting their use in NMH.Öğe Investigation of optimum production conditions and the stability of ?-cyclodextrin-perfluorocarbon nanocone clusters for histotripsy applications(2024) Mustafa, Waleed; Hall, Sarah; Huynh, Laura; Mannasse, Rachel; Lüleburgaz, Serter; Vlaisavljevich, Eli; Yüksel Durmaz, YaseminNanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ?-cyclodextrin (?CD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ?CD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ?CD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster’s particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.Öğe Ionic liquid based treatment - A potential strategy to modify bacterial cellulose(Wiley, 2023) Munir, Muneeba; Muhammad, Nawshad; Uroos, Maliha; Mustafa, Waleed; Sharif, FaizaThe constant need for advanced materials led by modern research continues the exploitation of old remedies and innovation to find new solutions. The use of ionic liquids (ILs) as solvents has revolutionized modern chemical research. The non-toxic green technology has inspired new paradigms in chemical reactions and synthesis. Developing nontoxic materials for industrial and biomedical applications has endorsed the use of ILs in synthesis and fabrication. In terms of biomedical materials, the exploration for novel technologies to deal with chronic and nonhealing injuries desires degradable materials. One of the vastly used biomaterials is cellulose, which is nondegradable on its own unless digested by special enzymes produced by bacteria in nature. Bacterial cellulose (BC) is a naturally occurring more refined and purified form of cellulose which again is nondegradable on its own. Looking for technologies that can modify the BC in situ or ex situ is a challenge. This review is bound to give insight into the current scientific research being conducted to render BC degradable for biomedical applications. The data has been collected through Clarivate analysis, Google search, PubMed Central Identifier (PMCID), and Research Gate. The lack of available literature on this topic allowed us to include all the articles related to the subject as old as 1988 onwards.Öğe Nanoparticle-mediated histotripsy using dual-frequency pulsing methods(2024) Edsall, Connor; Huynh, Laura; Mustafa, Waleed; Hall, Timothy L.; Yüksel Durmaz, Yasemin; Vlaisavljevich, EliObjective: Nanoparticle-mediated histotripsy (NMH) is a novel ablation method that combines nanoparticles as artificial cavitation nuclei with focused ultrasound pulsing to achieve targeted, non-invasive, and cell-selective tumor ablation. The study described here examined the effect of dual-frequency histotripsy pulsing on the cavitation threshold, bubble cloud characteristics, and ablative efficiency in NMH. High-speed optical imaging was used to analyze bubble cloud characteristics and to measure ablation efficiency for NMH inside agarose tissue phantoms containing perfluorohexane-filled nanocone clusters, which were previously developed to reduce the histotripsy cavitation threshold for NMH. Methods: Dual-frequency histotripsy pulsing was applied at a 1:1 pressure ratio using a modular 500 kHz and 3 MHz dual-frequency array transducer. Optical imaging results revealed predictable, well-defined bubble clouds generated for all tested cases with similar reductions in the cavitation thresholds observed for single-frequency and dual-frequency pulsing. Results: Dual-frequency pulsing was seen to nucleate small, dense clouds in agarose phantoms, intermediate in size of their component frequencies but closer in area to that of the higher component frequency. Red blood cell experiments revealed complete ablations were generated by dual-frequency NMH in all phantoms in <1500 pulses. This result was a significant increase in ablation efficiency compared with the ?4000 pulses required in prior single-frequency NMH studies. Conclusion: Overall, this study indicates the potential for using dual-frequency histotripsy methods to increase the ablation efficacy of NMH.











