Finite Element Modelling of a Cellular Electric Microenvironment

This method helps predict the electric microenvironment of a cell seated onto a fiber scaffold, such as the extracellular matrix. There are two main advantages that arise from insilico modeling. The prediction of experimental conditions is 3D, while optimization is enabled by the ease of parameter change.

Electrical stimulation aids the regeneration of multiple tissues. This model in similar insilico models will help the optimization of the stimulation parameters. To begin, open the COMSOL software and select blank model.

In model builder, right click on global definitions, select parameters and add parameters according to table one in the text manuscript. You can add them one by one, or load them from a text file. In the model builder under global definitions, right-click material and select blank material to add materials.

To add material properties, go to the settings of the newly added material, then expand material properties and select electrical conductivity from basic properties. Press the plus symbol to add property. Repeat this process for relative permittivity.

Fill in the current material properties, according to table two from the text manuscript. Next, left click on add component from the home tab and select 3D to add a new component node in the model builder. Again, right-click on geometry, left-click on insert sequence.

Then double-click on the full model and select the appropriate sequence. Under the current component node in the model builder, right click materials and select material link. Associate materials for each component in this order, surrounding substance, coats and cores.

In the settings tab for the surrounding substance, expand the selection list to choose media selection. Expand the link settings and choose the appropriate material like culture media from the drop-down list. To see the domains within the culture media block, activate the transparency button in the graphics tab.

Configure the other material links in the same manner. In the model builder, left click current component, select add physics, then expand the AC/DC module to select the electric current module and click add to component. To define boundary conditions, select the XY view in the graphics tab.

Go to the model builder again, right click on the electric currents node and select ground. Next, keep the selection switch for the boundary selection active. Left click on the highest surrounding substance face parallel to the XZ plane and add boundary five in the boundary selection box.

In the model builder, right click on the electric current node and select terminal. Keeping the boundary selection active, left click on the lowest surrounding substance face parallel to the XZ plane and add boundary too in the boundary selection box. Then by expanding the terminal selection, select a voltage in the terminal type dropdown list and fill in V zero for voltage.

Under global definitions in model builder, left click parameters and change the parameter theta to the fiber orientation angle desired for simulation. Expand the components node for each component in the model builder, then right, click on geometry and select build all. Left-click the model root node in the model builder and open the add study tab.

Select stationary study, and right-click add study. Under the newly added study, left-click on step one, expand study extensions, check the adaptive mesh refinement box and click compute to obtain the refined mesh. Left-click the model root node in the model builder and open the add study tab, select stationary study and right click add study.

Under the newly added study, left-click on step one, expand mesh selection and select the mesh generated in the adaptive mesh refinement study. Proceed by right clicking on the compute button. Right-click on the results node in the model builder and select 3D plot group to edit settings.

Change the label to charge density and select the parametric study data set by expanding dataset from the dropdown list. Then in the color legend, check the boxes for show legends and show maximum and minimum values. Again under the results node, right-click charged density to select volume and proceed to edit the settings tab.

Expand the data tab, then select from parent and fill in EC.RHOQ in the expression box. Check the manual color range box from the range tab and set the minimum and maximum to minus 0.3 and 0.3 respectively. Expand coloring and style and set coloring to color table and color table to wave.

Check the color legend box and symmetries color range. Right-click volume and model builder and select filter. Go to the settings tab and fill in the logical expression for inclusion.

Left-click on the plot button to visualize results in the graphics window. In this analysis, five different geometrical complexity stages that influenced the simulation result are displayed. A mesh that is too coarse, can hide relevant information.

Using the adaptive mesh refinement, a mesh with smaller elements is obtained, as it is required for accurate results. At different levels of complexity for the fibrous matte model, the strength of the electric field was influenced by the alignment of the fibers with respect to the potential gradient. Additionally, the fiber alignment angled to electric potential gradient impacts the space charged density in surrounding cell culture media.

In the scaffold fiber orientation study, the study state RNC model predictions were illustrated when fibers were parallel or perpendicular to the electrical field. The charge density and current density were influenced by scaffold fiber alignment relative to the electric field. This protocol can be used to investigate the impact of parameter changes on the charge density around a fiber scaffold segment.

It is important to remember, that by changing model parameters, such as data or material properties, the resulting charge density range may change significantly. For best visualization, the range must be optimized such that maximum variability in the charged density can be observed.