Interaction of endothelial cells with fluid flow in a biomimetic environment

At the interfaces between the blood and tissues are blood vessels with their endothelial cell layers containing the cells that directly interact with the blood.  Everything from lipid transport, to the blood brain barrier, to movement of oxygen into and out of the blood stream, to damage that leads to vascular diseases such as atherosclerosis, to vascular complications of diabetes, to movement of drugs transported in the blood into tissues, starts with critical functions of the endothelial cells and/or their damage in disease development. Despite these important functions of the endothelium, studying endothelial function is difficult, and model systems rarely mimic the natural blood vessels. 

 

We will begin the development of endothelial layers in mimetic vascular network models that will allow us to further pursue questions of localized drug delivery, vascular graft responses, and endothelial signal transduction in response to altered flow. We will first optimize endothelial cell growth on PDMS surfaces modified with various adhesion substrate proteins. PDMS is ideal for micromachining transparent micro-channels and can be easily molded into vascular channels similar to those found in tissues. In addition, we will develop computational models for flow in the chambers currently used by us for signal transduction and use those models to identify the best configurations to carry out in the next set of experimental studies. Finally, we will plan and produce relatively simple channel systems so that we can use experimental data we obtain from current simple flow systems to allow production of more complicated models.  

 

In the future, the interplay between the modeling and experimental data collection will allow us to better understand the mechanical effects of microvasculature flow on endothelial function and on treatments where efficacy depends on localized flow (e.gs. vascular grafts and drug delivery).