2,548 research outputs found

    Radial Dynamics of Pickering-stabilised Endoskeletal Antibubbles and Their Components in Pulsed Ultrasound

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    Liquids containing microscopic antibubbles may have theranostic applications in harmonic diagnostic ultrasonic imaging and in ultrasound-assisted drug delivery. Presently there are no known agents available with the acoustic properties required for use in both of these applications. The Pickering-stabilised antibubble may possess the de- sired acoustic properties to be such a theranostic agent. An antibubble is a gas bubble containing at least one incompressible core. An antibubble is inherently unstable and thus needs to be stabilised to exist for longer than a moment. One such stabilising method, involving the adsorption of nanoparticles to gasā€“liquid interfaces, is called Pickering stabilisation. A Pickering-stabilised antibubble responds to an incident sound ļ¬eld by means of radial pulsation and other, more complicated, dynamics. Despite the potential application of microscopic antibubbles in theranostics, their dynamic behaviour and the acoustic regimes in which this behaviour occurs are not known. The purpose of this research was to predict the dynamic response of Pickering- stabilised antibubbles to pulsed ultrasound, and to identify and quantify the contribution of each of the Pickering-stabilised antibubble components to that behaviour. Radial excursions of antibubbles and their components during ultrasound exposure were extracted from high-speed footage. The applied ultrasound had a centre frequency of 1 MHz and pressure amplitudes between 0.20 MPa and 1.30 MPa. Moreover, damping coeļ¬ƒcients, pulsation phases, and excursions of antibubbles and antibubble components were computed with equations describing a forced massā€“springā€“dashpot system and an adapted Rayleigh-Plesset equation. Over a range of driving pressure amplitudes, fragmentation thresholds were computed for antibubbles of varying size, core volume, shell stiļ¬€ness, and driving frequency. In addition, the feasibility of an antibubble component for the disruption of cell walls was tested. From the experimental data, it was found that antibubble contractions and expansions were symmetrical and predictable at an acoustic amplitude of 0.20 MPa, whilst the pulsations were asymmetrical and less predictable at an acoustic amplitude of 1.00 MPa. These results show that the presence of the core inside of the antibubble hampers the contraction of a collapsing antibubble and ameliorates its stability. Consequently, Pickering-stabilised antibubbles appear to be feasible candidates for ultrasonic imaging, with greater stability than the agents currently in use. Micron-sized antibubbles, much smaller than resonant size, were computed to have a pulsation phase diļ¬€erence of up to 16 th of a cycle with respect to free gas bubbles. The diļ¬€erence in oscillation phase is a result of the increased damping coefļ¬cient caused by the friction of the internal components and shell of the antibubble. This indicates that altering the damping of the shell or skeletal material of minute antibubbles can alter the degree to which the particleā€™s oscillation is in phase with the sound ļ¬eld. The shell stiļ¬€ness of Pickering-stabilised microbubbles without incompressible contents was measured to be 7.6 N māˆ’1 throughout low-amplitude sonication. Un- der high-amplitude sonication, the maximum expansions of microbubbles, measured from high-speed camera footage, were either agreeing with those computed for Pickering-stabilised microbubbles or corresponding to greater values. The diļ¬€ering oscillation amplitudes for similarly sized microbubbles is attributed to shell disruption of diļ¬€erent severity. For a 3-Ī¼m radius antibubble with a 90% core radius, subjected to a pulse of centre frequency 1 MHz, the fragmentation threshold was computed to drastically increase with shell stiļ¬€ness. At a driving frequency of 13 MHz, the fragmentation threshold was computed to correspond to a mechanical index less than 0.4, irrespective of shell stiļ¬€ness. Shell stiļ¬€ness changes the resonance frequency, and thus the fragmentation threshold of antibubbles. This means that the resonance frequency of an extremely low concentration and quantity of homogeneous agent can be determined using microscopy. At driving frequencies above 1 MHz, the fragmentation threshold was computed to correspond to a mechanical index of less than 0.5, irrespective of shell stiļ¬€ness. Antibubbles exposed to high-amplitude ultrasound were found to have an exponential fragment size distribution. This brings us closer to understanding and controlling disruption and material release for these particles. If the pressure of the regime is known, the number of antibubble fragments produced can be theoretically determined. Under low-amplitude ultrasound exposure, hydrophobic particles, a common component of antibubbles, were observed to jet through wood ļ¬bre cell walls, without causing visible internal structural damage to these cells. Hydrophobic particles can thus act as inertial cavitation nuclei which collapse asymmetrically close to solid boundaries such as wood pulp ļ¬bres. This indicates that hydrophobic particles on their own may be used for applications such as trans-dermal drug delivery. The dynamic response of Pickering-stabilised antibubbles to ultrasound has been predicted. Furthermore the respective behaviour of Pickering-stabilised antibubble components under theranostic ultrasound conditions has been identiļ¬ed. This work has led to a straightforward way to determine the elasto-mechano properties of small samples of contrast agent. Whilst possessing some theranostic properties, Pickering-stabilised antibubbles may be more suitable as replacements for current diagnostic agents. Hydrophobic particles, a current constituent of the Pickering-stabilised antibubble, may however, prove to be promising theranostic agents

    Numerical Simulations of Cavitating Bubbles in Elastic and Viscoelastic Materials for Biomedical Applications

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    The interactions of cavitating bubbles with elastic and viscoelastic materials play a central role in many biomedical applications. This thesis makes use of numerical modeling and data-driven approaches to characterize soft biomaterials at high strain rates via observation of bubble dynamics, and to model burst-wave lithotripsy, a focused ultrasound therapy to break kidney stones. In the first part of the thesis, a data assimilation framework is developed for cavitation rheometry, a technique that uses bubble dynamics to characterize soft, viscoelastic materials at high strain-rates. This framework aims to determine material properties that best fit observed cavitating bubble dynamics. We propose ensemble-based data assimilation methods to solve this inverse problem. This approach is validated with surrogate data generated by adding random noise to simulated bubble radius time histories, and we show that we can confidently and efficiently estimate parameters of interest within 5% given an iterative Kalman smoother approach and an ensemble- based 4D-Var hybrid technique. The developed framework is applied to experimental data in three distinct settings, with varying bubble nucleation methods, cavitation media, and using different material constitutive models. We demonstrate that the mechanical properties of gels used in each experiment can be estimated quickly and accurately despite experimental inconsistencies, model error, and noisy data. The framework is used to further our understanding of the underlying physics and identify limitations of our bubble dynamics model for violent bubble collapse. In the second part of the thesis, we simulate burst-wave lithotripsy (BWL), a non- invasive treatment for kidney stones that relies on repeated short bursts of focused ultrasound. Numerical approaches to study BWL require simulation of acoustic waves interacting with solid stones as well as bubble clouds which can nucleate ahead of the stone. We implement and validate a hypoelastic material model, which, with the addition of a continuum damage model and calibration of a spherically- focused transducer array, enables us to determine how effective various treatment strategies are with arbitrary stones. We present a preliminary investigation of the bubble dynamics occurring during treatment, and their impact on damage to the stone. Finally, we propose a strategy to reduce shielding by collapsing bubbles ahead of the stone via introduction of a secondary, low-frequency ultrasound pulse during treatment.</p

    Microwave - Plasma based Thermal Treatment of Asphaltene - derived Carbon Fibres

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    Asphaltene-based carbon fibres have emerged as a significant and sustainable alternative to conventional Polyacrylonitrile (PAN)-based carbon fibres, owing to their abundant availability, aromatic nature, and high carbon content. This thesis investigates the utilization of asphaltenes, extracted from bitumen in Alberta oilsands, as a valuable precursor for the manufacturing of carbon fibres. The precursor employed in commercial carbon fibre manufacturing accounts for approximately 51% of the total production cost. The utilization of asphaltene as a precursor offers the potential for cost reduction in carbon fibre production. With this reduced cost, carbon fibres, renowned for their exceptional mechanical properties such as high stiffness, remarkable tensile strength, chemical resistance, and capacity to withstand higher temperatures, can find applications across wide range of industries. Moreover, this cost reduction also contributes to the economic viability of converting industrial waste into valuable products. Conventional post-treatment processes in carbon fibre manufacturing, such as furnace stabilization and carbonization, play a crucial role in the production process, demanding considerable time and energy resources. Post-treatment alone, comprising 38% of the overall cost of carbon fibre production, significantly impacts the economic aspects of the manufacturing process. In this thesis, asphaltenes derived from Alberta oilsands are pretreated with solvents such as pentane and toluene to remove coke residues. Later, these asphaltenes are transformed into fibres through the process of melt spinning using a twin-screw extruder. An innovative approach involving microwave plasma thermal treatment, replacing conventional post-treatment methods, specifically carbonization, is then applied to convert these fibres into carbon fibres. The study of microwave plasma behaviour and its corresponding temperatures is successfully conducted through the use of Multiphysics Finite Element Analysis (FEA). An experimental optimization study involving the thermal treatment of stabilized fibres under varying power levels and treatment durations using microwave plasma has been conducted. The study successfully implemented microwave plasma techniques to achieve carbonization of asphaltene fibres, resulting in an increase in carbon content and the development of a well-ordered crystalline structure. The Element analysis revealed the dynamic changes in elemental composition, showcasing the effectiveness of microwave plasma in achieving carbonization. X-ray diffraction patterns and Raman spectroscopy provided valuable insights into the structural evolution, highlighting the unique impact of microwave plasma treatment on the development of a layered graphite-like structure and higher graphitic content. However, it is essential to acknowledge limitations, such as the observed surface damage and reduced tensile strength in microwave-plasma treated fibres, emphasizing the need for further optimization of parameters to maximize the benefits of this innovative approach. Overall, this research contributes valuable insights to the field of carbon fibre manufacturing, paving the way for more sustainable and economically feasible production processes with the utilization of asphaltene-based precursors and microwave plasma techniques

    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    Primary liver cancer, consisting primarily of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a heterogeneous malignancy with a dismal prognosis, resulting in the third leading cause of cancer mortality worldwide [1, 2]. It is characterized by unique histological features, late-stage diagnosis, a highly variable mutational landscape, and high levels of heterogeneity in biology and etiology [3-5]. Treatment options are limited, with surgical intervention the main curative option, although not available for the majority of patients which are diagnosed in an advanced stage. Major contributing factors to the complexity and limited treatment options are the interactions between primary tumor cells, non-neoplastic stromal and immune cells, and the extracellular matrix (ECM). ECM dysregulation plays a prominent role in multiple facets of liver cancer, including initiation and progression [6, 7]. HCC often develops in already damaged environments containing large areas of inflammation and fibrosis, while CCA is commonly characterized by significant desmoplasia, extensive formation of connective tissue surrounding the tumor [8, 9]. Thus, to gain a better understanding of liver cancer biology, sophisticated in vitro tumor models need to incorporate comprehensively the various aspects that together dictate liver cancer progression. Therefore, the aim of this thesis is to create in vitro liver cancer models through organoid technology approaches, allowing for novel insights into liver cancer biology and, in turn, providing potential avenues for therapeutic testing. To model primary epithelial liver cancer cells, organoid technology is employed in part I. To study and characterize the role of ECM in liver cancer, decellularization of tumor tissue, adjacent liver tissue, and distant metastatic organs (i.e. lung and lymph node) is described, characterized, and combined with organoid technology to create improved tissue engineered models for liver cancer in part II of this thesis. Chapter 1 provides a brief introduction into the concepts of liver cancer, cellular heterogeneity, decellularization and organoid technology. It also explains the rationale behind the work presented in this thesis. In-depth analysis of organoid technology and contrasting it to different in vitro cell culture systems employed for liver cancer modeling is done in chapter 2. Reliable establishment of liver cancer organoids is crucial for advancing translational applications of organoids, such as personalized medicine. Therefore, as described in chapter 3, a multi-center analysis was performed on establishment of liver cancer organoids. This revealed a global establishment efficiency rate of 28.2% (19.3% for hepatocellular carcinoma organoids (HCCO) and 36% for cholangiocarcinoma organoids (CCAO)). Additionally, potential solutions and future perspectives for increasing establishment are provided. Liver cancer organoids consist of solely primary epithelial tumor cells. To engineer an in vitro tumor model with the possibility of immunotherapy testing, CCAO were combined with immune cells in chapter 4. Co-culture of CCAO with peripheral blood mononuclear cells and/or allogenic T cells revealed an effective anti-tumor immune response, with distinct interpatient heterogeneity. These cytotoxic effects were mediated by cell-cell contact and release of soluble factors, albeit indirect killing through soluble factors was only observed in one organoid line. Thus, this model provided a first step towards developing immunotherapy for CCA on an individual patient level. Personalized medicine success is dependent on an organoids ability to recapitulate patient tissue faithfully. Therefore, in chapter 5 a novel organoid system was created in which branching morphogenesis was induced in cholangiocyte and CCA organoids. Branching cholangiocyte organoids self-organized into tubular structures, with high similarity to primary cholangiocytes, based on single-cell sequencing and functionality. Similarly, branching CCAO obtain a different morphology in vitro more similar to primary tumors. Moreover, these branching CCAO have a higher correlation to the transcriptomic profile of patient-paired tumor tissue and an increased drug resistance to gemcitabine and cisplatin, the standard chemotherapy regimen for CCA patients in the clinic. As discussed, CCAO represent the epithelial compartment of CCA. Proliferation, invasion, and metastasis of epithelial tumor cells is highly influenced by the interaction with their cellular and extracellular environment. The remodeling of various properties of the extracellular matrix (ECM), including stiffness, composition, alignment, and integrity, influences tumor progression. In chapter 6 the alterations of the ECM in solid tumors and the translational impact of our increased understanding of these alterations is discussed. The success of ECM-related cancer therapy development requires an intimate understanding of the malignancy-induced changes to the ECM. This principle was applied to liver cancer in chapter 7, whereby through a integrative molecular and mechanical approach the dysregulation of liver cancer ECM was characterized. An optimized agitation-based decellularization protocol was established for primary liver cancer (HCC and CCA) and paired adjacent tissue (HCC-ADJ and CCA-ADJ). Novel malignancy-related ECM protein signatures were found, which were previously overlooked in liver cancer transcriptomic data. Additionally, the mechanical characteristics were probed, which revealed divergent macro- and micro-scale mechanical properties and a higher alignment of collagen in CCA. This study provided a better understanding of ECM alterations during liver cancer as well as a potential scaffold for culture of organoids. This was applied to CCA in chapter 8 by combining decellularized CCA tumor ECM and tumor-free liver ECM with CCAO to study cell-matrix interactions. Culture of CCAO in tumor ECM resulted in a transcriptome closely resembling in vivo patient tumor tissue, and was accompanied by an increase in chemo resistance. In tumor-free liver ECM, devoid of desmoplasia, CCAO initiated a desmoplastic reaction through increased collagen production. If desmoplasia was already present, distinct ECM proteins were produced by the organoids. These were tumor-related proteins associated with poor patient survival. To extend this method of studying cell-matrix interactions to a metastatic setting, lung and lymph node tissue was decellularized and recellularized with CCAO in chapter 9, as these are common locations of metastasis in CCA. Decellularization resulted in removal of cells while preserving ECM structure and protein composition, linked to tissue-specific functioning hallmarks. Recellularization revealed that lung and lymph node ECM induced different gene expression profiles in the organoids, related to cancer stem cell phenotype, cell-ECM integrin binding, and epithelial-to-mesenchymal transition. Furthermore, the metabolic activity of CCAO in lung and lymph node was significantly influenced by the metastatic location, the original characteristics of the patient tumor, and the donor of the target organ. The previously described in vitro tumor models utilized decellularized scaffolds with native structure. Decellularized ECM can also be used for creation of tissue-specific hydrogels through digestion and gelation procedures. These hydrogels were created from both porcine and human livers in chapter 10. The liver ECM-based hydrogels were used to initiate and culture healthy cholangiocyte organoids, which maintained cholangiocyte marker expression, thus providing an alternative for initiation of organoids in BME. Building upon this, in chapter 11 human liver ECM-based extracts were used in combination with a one-step microfluidic encapsulation method to produce size standardized CCAO. The established system can facilitate the reduction of size variability conventionally seen in organoid culture by providing uniform scaffolding. Encapsulated CCAO retained their stem cell phenotype and were amendable to drug screening, showing the feasibility of scalable production of CCAO for throughput drug screening approaches. Lastly, Chapter 12 provides a global discussion and future outlook on tumor tissue engineering strategies for liver cancer, using organoid technology and decellularization. Combining multiple aspects of liver cancer, both cellular and extracellular, with tissue engineering strategies provides advanced tumor models that can delineate fundamental mechanistic insights as well as provide a platform for drug screening approaches.<br/

    Temperature Reduction Technologies Meet Asphalt Pavement: Green and Sustainability

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    This Special Issue, "Temperature Reduction Technologies Meet Asphalt Pavement: Green and Sustainability", covers various subjects related to advanced temperature reduction technologies in bituminous materials. It can help civil engineers and material scientists better identify underlying views for sustainable pavement constructions

    Proceedings of SIRM 2023 - The 15th European Conference on Rotordynamics

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    It was our great honor and pleasure to host the SIRM Conference after 2003 and 2011 for the third time in Darmstadt. Rotordynamics covers a huge variety of different applications and challenges which are all in the scope of this conference. The conference was opened with a keynote lecture given by Rainer Nordmann, one of the three founders of SIRM ā€œSchwingungen in rotierenden Maschinenā€. In total 53 papers passed our strict review process and were presented. This impressively shows that rotordynamics is relevant as ever. These contributions cover a very wide spectrum of session topics: fluid bearings and seals; air foil bearings; magnetic bearings; rotor blade interaction; rotor fluid interactions; unbalance and balancing; vibrations in turbomachines; vibration control; instability; electrical machines; monitoring, identification and diagnosis; advanced numerical tools and nonlinearities as well as general rotordynamics. The international character of the conference has been significantly enhanced by the Scientific Board since the 14th SIRM resulting on one hand in an expanded Scientific Committee which meanwhile consists of 31 members from 13 different European countries and on the other hand in the new name ā€œEuropean Conference on Rotordynamicsā€. This new international profile has also been emphasized by participants of the 15th SIRM coming from 17 different countries out of three continents. We experienced a vital discussion and dialogue between industry and academia at the conference where roughly one third of the papers were presented by industry and two thirds by academia being an excellent basis to follow a bidirectional transfer what we call xchange at Technical University of Darmstadt. At this point we also want to give our special thanks to the eleven industry sponsors for their great support of the conference. On behalf of the Darmstadt Local Committee I welcome you to read the papers of the 15th SIRM giving you further insight into the topics and presentations

    Friction of biomechanical interfaces

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    Flows of viscoplastic fluids

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    Biofidelic simulations of embryonic joint growth and morphogenesis

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    During skeletal development, the opposing surfaces in the joint mould into interlocking and reciprocal shapes in a process called morphogenesis. Morphogenesis is critical to the health and function of the joint, and yet, little is known about the process of joint morphogenesis. For example, how do different joints acquire their specific shapes? Which cellular processes underlie joint shaping and how are they regulated? However, it is known that fetal movements are critical to joint development, with alterations or absences of movement being implicated in multiple pre- and post-natal musculoskeletal conditions. This doctorate explored the cell-level dynamics governing joint growth and the implication of movements in regulating them, using novel biofidelic and mechanobiological models of joint growth. Cell-level data from wild type zebrafish larvae were tracked and synthesised in a biofidelic simulation of zebrafish jaw joint growth. Growth characteristics were quantified revealing a strong anisotropy (Chapter 3). Next, zebrafish larvae were immobilised using drug treatment. The material properties of the zebrafish jaw cartilage were measured using nano-indentation in the presence or absence of movement showing a delay in cartilage stiffening in immobilised larvae (Chapter 4). Then, I developed a novel mechanobiological model of zebrafish jaw joint growth, which identified a correlation between growth characteristics and the dynamic patterns of mechanical stimuli experienced by joint elements over jaw motion (Chapter 5). Finally, local growth rates were characterised in the mouse elbow in the presence or absence of skeletal muscles. Spatial heterogeneity in the growth rates correlated with the emergence of specific shape features at the level of the condyles. Immobilisation led to disruption of the local growth rates correlated with failed shape differentiation of the condyles. The relative contribution of key cell activities to growth such as cell volume expansion, cell number increases and extracellular matrix expansion, were shown to vary over time in both wild types and muscleless-limbs and to be altered in the absence of skeletal muscles (Chapter 6). This research offers avenues for improvement in simulations of joint development and potentially other organs. It provides fundamental advance in our understanding of mechanoregulation in the developing joint and increases our understanding of the origins of musculoskeletal abnormalities.Open Acces
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