Multiscale computational modeling of aortic valve calcification.

Calcific aortic valve disease (CAVD) is a common cardiovascular disease that affects millions of people worldwide. The disease is characterized by the formation of calcium nodules on the aortic valve leaflets, which can lead to stenosis and heart failure if left untreated. The pathogenesis of CAVD is still not well understood, but involves several signaling pathways, including the transforming growth factor beta (TGF ß ) pathway. In this study, we developed a multiscale computational model for TGF ß -stimulated CAVD. The model framework comprises cellular behavior dynamics, subcellular signaling pathways, and tissue-level diffusion fields of pertinent chemical species, where information is shared among different scales. Processes such as endothelial to mesenchymal transition (EndMT), fibrosis, and calcification are incorporated. The results indicate that the majority of myofibroblasts and osteoblast-like cells ultimately die due to lack of nutrients as they become trapped in areas with higher levels of fibrosis or calcification, and they subsequently act as sources for calcium nodules, which contribute to a polydispersed nodule size distribution. Additionally, fibrosis and calcification processes occur more frequently in regions closer to the endothelial layer where the cell activity is higher. Our results provide insights into the mechanisms of CAVD and TGF ß signaling and could aid in the development of novel therapeutic approaches for CAVD and other related diseases such as cancer. More broadly, this type of modeling framework can pave the way for unraveling the complexity of biological systems by incorporating several signaling pathways in subcellular models to simulate tissue remodeling in diseases involving cellular mechanobiology.

Characterization of Fluidic-Barrier-Based Particle Generation in Centrifugal Microfluidics.

The fluidic barrier in centrifugal microfluidic platforms is a newly introduced concept for making multiple emulsions and microparticles. In this study, we focused on particle generation application to better characterize this method. Because the phenomenon is too fast to be captured experimentally, we employ theoretical models to show how liquid polymeric droplets pass a fluidic barrier before crosslinking. We explain how secondary flows evolve and mix the fluids within the droplets. From an experimental point of view, the effect of different parameters, such as the barrier length, source channel width, and rotational speed, on the particles' size and aspect ratio are investigated. It is demonstrated that the barrier length does not affect the particle's ultimate velocity. Unlike conventional air gaps, the barrier length does not significantly affect the aspect ratio of the produced microparticles. Eventually, we broaden this concept to two source fluids and study the importance of source channel geometry, barrier length, and rotational speed in generating two-fluid droplets.

Droplet and Particle Generation on Centrifugal Microfluidic Platforms: A Review.

The use of multiphase flows in microfluidics to carry dispersed phase material (droplets, particles, bubbles, or fibers) has many applications. In this review paper, we focus on such flows on centrifugal microfluidic platforms and present different methods of dispersed phase material generation. These methods are classified into three specific categories, i.e., step emulsification, crossflow, and dispenser nozzle. Previous works on these topics are discussed and related parameters and specifications, including the size, material, production rate, and rotational speed are explicitly mentioned. In addition, the associated theories and important dimensionless numbers are presented. Finally, we discuss the commercialization of these devices and show a comparison to unveil the pros and cons of the different methods so that researchers can select the centrifugal droplet/particle generation method which better suits their needs.