The potential of physiologically relevant in vitro cell culture models for studying physiological and pathophysiological phenomena has been widely recognized as replacements for animal and conventional in vitro models. To create models that accurately replicate the structure and function of tissues and organs, it is essential to comprehend the biophysical and mechanical features of the extracellular matrix (ECM) and incorporate them into the in vitro cell culture models. Therefore, we first aimed to investigate how nanotopography can modulate cell behaviors by studying cell behaviors on nanostructures of various aspect ratios on a cobalt-chromium-molybdenum (CoCrMo) alloy surface. We also explored the impact of nanofibrous membranes on the formation of alveolar epithelium, which is critical for lung alveolar interstitium chips. In addition, we investigated the effect of mechanical stretch on cell behaviors and focused on how the dimensionality of the stretch affects cell behaviors. To create physiologically relevant in vitro models based on our findings, we engineered a stem cell niche using a combination of nanofibrous membranes, mechanical stretch, and a soft substrate, and evaluated its impact on stem cell behaviors. Finally, we created a biomimetic human lung interstitium chip for application in physiological and pathophysiological in vitro studies.

The blood-brain barrier (BBB) is composed of brain microvascular endothelial cells (BMECs), pericytes, and astrocytic endfeet, which regulate the transport of molecules into and out of the brain. BMECs possess intrinsic barrier properties that limit the passage of approximately 98% of small molecules into the brain in healthy individuals. However, in some brain diseases, the BBB undergoes structural and functional alterations, which can contribute to disease progression. In this study, we aimed to investigate the BBB by exploring the effects of endothelial cell stretching and the optimal dimensionality of stretching to enhance endothelium barrier tightness in Chapter 2. Subsequently, we developed an endothelium gradient stretching device to further examine the stretching effect in Chapter 3. Additionally, we investigated the promotion of endothelium tightness through the use of electrospun fibers, wherein we controlled the pore size. Based on these findings, we designed and fabricated an organ chip model that incorporates mechanical stretching, microfluidic techniques, electrospun fibers, and hydrogel extracellular matrix (ECM). The results of permeability testing demonstrated that this chip significantly improved the tightness of microvascular selective transport ability and has the potential to be used in drug sorting for central nervous system (CNS) diseases.

In this research, we aimed to develop thin-film devices on a polymer substrate and an alternative 3D-printed device with macroelectrodes for treating gastrointestinal (GI) conditions. First, the fabrication of thin-film devices was demonstrated on a softening thiol-ene/acrylate polymer utilizing titanium nitride (TiN) as electrode material. This was achieved by utilizing cleanroom fabrication processes such as photolithography, wet and dry etching. The functionality of the device was shown by performing electrochemical characterization tests, mainly cyclic voltammetry, electrochemical impedance spectroscopy, and voltage transient. We synthesized a novel thiol-ene/acrylate polymer based on 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), trimethylolpropanetris (3-mercaptopropionate) (TMTMP), and polyethylene glycol diacrylate (PEGDA). We show that this stretchable shape memory polymer substrate is well suited for cleanroom processes. Finally, for the high throughput of the wearable devices with electrodes size 10 mm in diameter, we implemented single electrode fabrication using printed circuit boards (PCBs) and depositing gold (Au) and TiN on the plated side of PCBs utilizing the sputtering tool. This step was followed by the assembly of those single electrodes on the flexible 3D printed device. We showed that the TiN electrode material performed better in terms of charge storage capacity and charge injection capacity than the widely used stainless steel electrode material …