Despite a recognized value in nowadays research, conventional two-dimensional (2D) cell cultures still fail to provide accurate prediction of tissue functions and behavior in vivo. In fact, cells grown on flat tissue culture substrates can differ considerably in their morphology, cell-cell and cell-matrix interactions, and differentiation from those growing in more physiological 3D environments. On the other hand, animal models may not adequately reproduce several features of human tumors, drug therapeutic responses, and autoimmune diseases. Recent advances in tissue engineering and biomedical technologies aim for the integration of biology with the spatial positioning capabilities allowed by microfabrication techniques. Physiological environments provided by extracellular matrices can be reproduced, besides the development of tissues, organs and tumors, paving the way to the so-called organ-on-chip technology. Microfluidic devices are generally fabricated as polydimethylsiloxane (PDMS) replicas of a lithographically obtained master. They allow a precise control on cells and tissue microenvironment, thus enabling the exposure of cells to medium flow. These aspects led to advanced systems, faithfully reproducing physiologically relevant conditions. Furthermore, the additional ability of these models lays in the chance of manufacturing optically transparent platforms, which might be observed in real time under the microscope, allowing a high-throughput imaging analysis. This thesis work highlights the power of these complex microengineered systems. In a first example, a "NAFLD-on-chip" device, exploiting a sinusoid-like geometry with a microchannel array to simulate the endothelial-like barrier, was used for high density 3D hepatocyte culture, with the aim to recapitulate the onset of nonalcoholic fatty liver disease. As a second example, a tumor-on-chip platform was developed to study the interaction between Cancer Stem Cell (CSCs) behavior with immune cells, in particular with Tumor-Associated Macrophages (TAMs). These models would accelerate and facilitate translational research to perform the screening of new therapies. In this sense, in vitro 3D models provide a bridge on the gap between traditional cell culture and animal models.

Advanced microfluidic devices mimicking the dynamic and 3D physiological microenvironment for diagnostic applications / Maria Chiara Simonelli - : . , 2016 Jul 22. ((27. ciclo

Advanced microfluidic devices mimicking the dynamic and 3D physiological microenvironment for diagnostic applications

2016-07-22

Abstract

Despite a recognized value in nowadays research, conventional two-dimensional (2D) cell cultures still fail to provide accurate prediction of tissue functions and behavior in vivo. In fact, cells grown on flat tissue culture substrates can differ considerably in their morphology, cell-cell and cell-matrix interactions, and differentiation from those growing in more physiological 3D environments. On the other hand, animal models may not adequately reproduce several features of human tumors, drug therapeutic responses, and autoimmune diseases. Recent advances in tissue engineering and biomedical technologies aim for the integration of biology with the spatial positioning capabilities allowed by microfabrication techniques. Physiological environments provided by extracellular matrices can be reproduced, besides the development of tissues, organs and tumors, paving the way to the so-called organ-on-chip technology. Microfluidic devices are generally fabricated as polydimethylsiloxane (PDMS) replicas of a lithographically obtained master. They allow a precise control on cells and tissue microenvironment, thus enabling the exposure of cells to medium flow. These aspects led to advanced systems, faithfully reproducing physiologically relevant conditions. Furthermore, the additional ability of these models lays in the chance of manufacturing optically transparent platforms, which might be observed in real time under the microscope, allowing a high-throughput imaging analysis. This thesis work highlights the power of these complex microengineered systems. In a first example, a "NAFLD-on-chip" device, exploiting a sinusoid-like geometry with a microchannel array to simulate the endothelial-like barrier, was used for high density 3D hepatocyte culture, with the aim to recapitulate the onset of nonalcoholic fatty liver disease. As a second example, a tumor-on-chip platform was developed to study the interaction between Cancer Stem Cell (CSCs) behavior with immune cells, in particular with Tumor-Associated Macrophages (TAMs). These models would accelerate and facilitate translational research to perform the screening of new therapies. In this sense, in vitro 3D models provide a bridge on the gap between traditional cell culture and animal models.
Microfluidics, tumor, liver-on-chip, microfabrication, in vitro models, diagnosis
Advanced microfluidic devices mimicking the dynamic and 3D physiological microenvironment for diagnostic applications / Maria Chiara Simonelli - : . , 2016 Jul 22. ((27. ciclo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/68711
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