Our work so far has focused on developing the analytica, numerical tools and developing the techniques for in vivo vascularization monitoring. We have developed a microfluidic technique for in vitro vascularization using xenotransplantation. To the best of our knowledge, this is the first demonstration of an in vivo vascularized transplanted tissue being detached from the living organism and later perfused in vitro. The dynamics of vascularization is still not well-understand and it is the core question we are tackling in our project. While observing embryonic development for extended times, we were also able to develop this microfluidic organ-on-chip system for kidney organoid vascularization. This system provides a solution for in vitro vascularized organoids, specifically kidney towards artificial kidney development.
The second achievement in the project is the oscillating hypoxia model that can be embedded to commercial organoid culturing platforms mimic real-world hypoxia conditions. We verified the sensitivity of cells adjacent to the microchannel to fluctuations of oxygen content in the microchannel as we monitored and calculated the frequency of oxygen probe signal oscillations. The calculated frequency and period of oscillations in the oxygen probe signal, correspond to the frequency and period of oxygen oscillations in the microchannel. Moreover, by monitoring the reactive oxygen species (ROS) production after each cycle of hypoxia/reoxygenation we further validated the reliability of our model to study the cycling hypoxia implication. To our knowledge, this is the first in vitro model, that can be an alternative to existing in vitro and in vivo models, that provides experimental evidence into the effect of heterogenous oxygen supply on pericapillary tissue, the swiftness of cellular response to oxygen fluctuations, regional blood flow regulation and red blood cell distribution.
The third achievement in the project is the numerical model we developed to simulate spontaneously generated RBC concentration fluctuations. Using this tool and the in vitro droplet model, we were able to demonstrate that RBC distritubtion in networks can be generating spontanenous oscillations which can explain the over-vascularization followed by pruning during embryonic development. This simulation generates two outputs: Droplets, a variable that contains comprehensive information about each droplet's position, and Evolution in Number of Droplets, which records how droplet distributions vary over time across channels. These results are critical for understanding flow dynamics, investigating oscillatory phenomena, and the implications of non-uniform RBC distributions.
