Glial scar size, inhibitor concentration, and growth of regenerating axons after spinal cord transection

A mathematical model has been formulated in accordance with cell chemotaxis and relevant experimental data. A three-dimensional lattice Boltzmann method was used for numerical simulation. The present study observed the effects of glial scar size and inhibitor concentration on regenerative axonal growth following spinal cord transection. The simulation test comprised two parts： （1） when release rates of growth inhibitor and promoter were constant, the effects of glial scar size on axonal growth rate were analyzed, and concentrations of inhibitor and promoters located at the moving growth cones were recorded. （2） When the glial scar size was constant, the effects of inhibitor and promoter release rates on axonal growth rate were analyzed, and inhibitor and promoter concentrations at the moving growth cones were recorded. Results demonstrated that （1） a larger glial scar and a higher release rate of inhibitor resulted in a reduced axonal growth rate. （2） The axonal growth rate depended on the ratio of inhibitor to promoter concentrations at the growth cones. When the average ratio was 〈 1.5, regenerating axons were able to grow and successfully contact target cells.

Flow dynamics analyses of pathophysiological liver lobules using porous media theory

Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule,is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvasculature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D computational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic,and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts（PTs） and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic lobules.Models modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow features in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our understanding of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules.

Epidermal restriction confers robustness to organ shapes

The shape of comparable tissues and organs is consistent among individuals of a given species,but how this consistency or robustness is achieved remains an open question.The interaction between morphogenetic factors determines organ formation and subsequent shaping,which is ultimately a mechanical process.Using a computational approach,we show that the epidermal layer is essential for the robustness of organ geometry control.Specifically,proper epidermal restriction allows organ asymmetry maintenance,and the tensile epidermal layer is sufficient to suppress local variability in growth,leading to shape robustness.The model explains the enhanced organ shape variations in epidermal mutant plants.In addition,differences in the patterns of epidermal restriction may underlie the initial establishment of organ asymmetry.Our results show that epidermal restriction can answer the longstanding question of how cellular growth noise is averaged to produce precise organ shapes,and the findings also shed light on organ asymmetry establishment.

Flow field analyses of a porous membrane-separated,double-layered microfluidic chip for cell co-culture

Organs-on-chips composed of a porous membrane-separated,double-layered channels are used widely in elucidating the effects of cell co-culture and flow shear on biological functions.While the diversity of channel geometry and membrane permeability is applied,their quantitative correlation with flow features is still unclear.Immersed boundary methods(IBM)simulations and theoretical modelling were performed in this study.Numerical simulations showed that channel length,height and membrane permeability jointly regulated the flow features of flux,penetration velocity and wall shear stress(WSS).Increase of channel length,lower channel height or membrane permeability monotonically reduced the flow flux,velocity and WSS in upper channel before reaching a plateau.While the flow flux in lower channel monotonically increased with the increase of each factor,the WSS surprisingly exhibited a biphasic pattern with first increase and then decrease with increase of lower channel height.Moreover,the transition threshold of maximum WSS was sensitive to the channel length and membrane permeability.Theoretical modeling,integrating the transmembrane pressure difference and inlet flow flux with chip geometry and membrane permeability,was in good agreement with IBM simulations.These analyses provided theoretical bases for optimizing flow-specified chip design and evaluating flow microenvironments of in vivo tissue.