Development of microfluidic models of cardiovascular diseases.

Myocardial infarction or heart attack remained the leading cause of death globally for over 30 years. Atherosclerosis, a chronic inflammatory disorder, underpins the pathological consequence of this deadly condition. Early detection of this disease presents demanding challenges because of the disease's multifactorial complexity. The interplay of flow patterns inside the blood vessel, endothelial dysfunction, the cellular and plasma components of the blood, and the extracellular matrix are all factors to consider. Existing two-dimensional (2D) in vitro and in vivo atherosclerosis models have several limitations because of the lack of physiological micro-and macro-environment parameters in vitro and inter-species differences in-vivo. Herein, we aim to develop in vivo relevance atherosclerosis models for understanding the disease pathogenicity and use them as drug testing devices for focused thrombosis treatment. In the first part of our study, we designed a site-specific atherothrombosis model on the microfluidic device to provide a universal platform for studying the crosstalk between blood cells and plaque components. The device consists of two interconnected microchannels, namely main and supporting channels: the former mimics the vessel geometry with different stenosis, and the latter introduces plaque components to the circulation simultaneously. The unique design allows the site-specific introduction of plaque components in stenosed channels ranging from 0 to above 50%, resulting in thrombosis, which has not been achieved previously. The device successfully mimics the geometry-dependent and shear-dependent thrombosis formation, confirming the reliability of our design. The device exhibits significant sensitivity to aspirin. Moreover, the device could be used in testing the targeted binding of the RGD (arginyl-glycyl-aspartic acid) labelled polymeric nanoparticles on the thrombus, extending the use of the device to examine targeted drug carriers. Next, the device is used to study the influence of different disease conditions on atherogenic pathogenicity. The device shows promising sensitivity in high glucose and inflammatory conditions in a dose-dependent manner. Finally, we modify our design to establish a microfluidic atherosclerosis model on the chip. We establish a vascular endothelial-smooth muscle cell co-culture model to study the influence of different atherogenic factors in monocyte transmigration and foam cell formation on-chip.

Magnetic Cationic Fluorinated Polymer Grafted Iron Oxide Nanoparticles for Efficient Multiple PFAS Removal

Per- and polyfluoroalkyl substances (PFAS) are a series of man-made compounds that have been widely used since the 1950’s. Although they are commonly used in daily life, the toxicity of PFAS to humans should not be neglected. Due to their uniquely stable chemical structure (arising from the strong carbon-fluorine bond) and moderate solubility in aqueous solutions, problems of water contamination and bioaccumulation have arisen, attracting novel proposals for their efficient removal. In our previous fundamental studies, we reported the effective (up to 90% removal) and selective sorption of one of the most commonly used PFAS, perfluorooctanoic acid (PFOA), by non-ionic perfluoropolyether (PFPE)-containing polymer in aqueous solutions. After incorporation of cationic quaternized ammonium groups, the capture of anionic PFOA by cationic perfluoropolyether (PFPE)-containing polymer was observed to be more efficient (~100%) compared with the non-ionic polymer. The cationic groups on the polymer contribute to the tight binding with PFOA via electrostatic attraction, and the presence of PFPE hydrophobic segments provides selective and additional PFOA sorption by fluorine-fluorine hydrophobic interactions. In this work, by using the reported design parameters, a series of non-ionic and cationic PFPE-containing polymers were synthesized and grafted on the surface of Fe3O4 nanoparticles for efficient multiple PFAS removal from contaminated aqueous systems. By grafting the fluorinated polymer on magnetic iron oxide (Fe3O4) particle, flexible recovery of the absorbent after sorption of PFAS was obtained via magnetic separation. We hope to develop these fluorinated materials as novel sorbents for rapid and efficient removal of PFAS at environmentally relevant concentrations by the end of the project.



Fahima Akther is the third year of PhD student, currently working on developing in vitro cardiovascular disease models. Her main interest is to develop physiological relevance atherosclerosis models to study the influence of atherogenic factors in disease progression. Another focus of her study is to modulate the disease model for testing new drugs. Before moving to Australia, she completed her master’s degree from Chonnam national university, South Korea and worked as a research assistant at the same university. She completed her Bachelor of Pharmacy in Bangladesh and worked as a registered pharmacist in her country. She also worked as a lecturer in the pharmacy department at the International Islamic University, Chittagong.

Xiao achieved his bachelor degree in Nanjing University of Chinese Medicine in 2017, majoring in Pharmaceutical Science. Then he came to Australia and completed his Masters studies in Molecular Biology at The University of Queensland in 2019. Now he is in his final year of his PhD under supervision of Prof Andrew Whittaker and Dr Cheng Zhang, in Australian Institute for Bioengineering and Nanotechnology (AIBN). His research focuses on developing novel devices for efficient PFAS removal from aqueous environments, including fluorinated polymers, crosslinked hydrogels and water permeable membranes.



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