While bicuspid aortic valve (BAV) shows different phenotypes associated with aortic aneurysm and valvular dysfunction due to aortic stenosis (AS), hemodynamics in patients with stenotic BAVs remains poorly understood. Here we address a study of the effects of valve phenotypes on aortic hemodynamics in different configurations of AS using an image-based subject-specific left ventricle (LV)-aorta integrated computational model. The model was built up by combining both MRI images and realistic motions of aortic valve, mitral valve, and LV apex as well as its contraction and dilatation of a healthy subject. Physiological boundary conditions were given based on a parameter-adjusted 0-1D cardiovascular model. Symmetrical BAV models with mild and severe stenosis were constructed with the orientation angle varying every 15° from 0° to 165° with regards to mitral valve while within a planar disc and the orientation effects on aortic hemodynamics were systematically investigated. Our results revealed that systolic jets in aorta were dominated by a combination of valve orientation and AS. Furthermore the hemodynamic indices of maximum wall shear stress (WSS), oscillatory shear index (OSI), and axial energy loss also demonstrated a feature of phenotype-and stenosis-dependency, pointing to the importance of taking into account the valve configuration in clinical decision-making on BAV patients.

Studies on platelet margination have shown that the platelets can effectively marginate at the microvessel wall in a multi-file flow of red blood cells (RBCs), whereas axially migrated RBCs push platelets toward the wall. However, it is unclear whether these results can be extended to capillaries, which potentially cause a single-file line of RBCs, or a so-called bolus flow. Our previous numerical results (Takeishi and Imai, 2017) showed that microparticles with a diameter of 1 μm (1-μm-MPs) were captured by a bolus flow of RBCs, instead of being marginated in capillaries. Herein we perform numerical simulations to clarify whether platelets are captured or escape from the vortex-like flow structures between RBCs. We demonstrate that platelets are also captured in a capillary whose diameter is 25% larger than that of RBCs at a physiologically-relevant hematocrit (Hct ～ 0.2), but the number of captured platelets is smaller than that of 1-μm-MPs. When the capillary diameter is comparable to that of RBCs, however, many platelets flow near the wall due to an unstable bolus flow resulting in a less number of captured platelets. These results suggest that the size effect reduces platelet capture events compared to 1-μm-MPs. We also investigate the effect of Hct and the non-dimensional shear rate (capillary number) on capture events. These findings may help not only to understand platelet adhesion in capillaries but also to develop therapeutic drug carriers.

Formation of vascular anastomoses is critical for the development of transplantable tissue-engineered grafts, because rapid blood perfusion is required for the maintenance of implanted tissue grafts. However, the process of vascular anastomosis remains unclear due to difficulties in observing vascular anastomosis after transplantation. Although several groups have developed in vitro models of vascular anastomosis, there is a lack of a suitable in vitro anastomosis model that includes perivascular cells. Therefore, we aimed to establish an in vitro vascular anastomosis model containing perivascular cells by a combination of human umbilical vein endothelial cell (HUVEC) monoculture and HUVEC-mesenchymal stem cell (MSC) coculture in a microfluidic device. We found that vascular formation was inhibited when HUVECs were seeded on both sides of gel scaffolds, but HUVECs formed vascular networks when they were seeded on one side only. Next, we tested a series of HUVEC:MSC ratios to induce vascular anastomoses. The results demonstrated that addition of MSCs induced vascular anastomosis. In particular, the number of vascular anastomoses was significantly increased at a HUVEC:MSC ratio of 2:8. The process of vascular anastomosis was further investigated by live-cell imaging of green fluorescent protein-expressing HUVECs, which revealed that vascular anastomoses with continuous lumens were constructed during days 8–10. Computational simulation of VEGF concentrations suggested that local VEGF gradients play important roles in vascular formation while the addition of MSCs was critical for anastomosis. This anastomosis model will provide insights for both the development of tissue-engineered grafts and for the construction of large tissues by assembling multiple tissue-engineered constructs.

Recently, many groups in the field of tissue engineering have attempted to utilize decellularized matrices for tissue regeneration. The decellularized matrices are known as a suitable tissue-engineered scaffold that retains the original structure of extracellular matrix (ECM) in the native tissue as well as its complex vasculature. While chemical reagents such as sodium dodecyl sulfate (SDS) are generally selected to fabricate the decellularized matrices due to its ease of use, high hydrostatic pressure (HHP) has become a powerful alternative to induce the decellularization without using any chemical reagents which have a possibility to provoke inflammatory response by the residual chemicals after in vivo transplantation. Although the HHP has been regarded as a promising tool to decellularize the native tissue, its fabrication mechanism remains still unknown. The aim of this study was to investigate the fabrication mechanism using HHP of 980 MPa to decellularize uterine tissues harvested from Sprague Dawley rats. As a result of histochemical analysis, we first reported that actin filaments in the uterine tissue were depolymerized by applying HHP. Our present findings will lead to the optimization of fabrication method using hydrostatic pressure to have an optimal decellularize matrix with complete micro- and macro-structures of the native tissue for tissue regeneration.