MECHANICAL LOADS

Biomechanical forces and locomotion in our bodies can have an impact on the endothelial cells, or “EC’s,” that exist within the boundaries of blood vessels. A large amount of this movement can result in cardiovascular complications, with shear stress and tensile strain being the two main culprits.

“Wall shear stress (WSS) defined as the tangential force per unit area imposed by blood flow,” has a large impact on endothelium function, with both low and high WSS resulting in ‘endothelial injury.’ (2).  Tensile strain is described as a mechanical strain causing elongation or deformation due to an applied force. It has been shown that the response of endothelial cells is highly dependent on whether these forces are applied simultaneously or separately, with each affecting the orientation of these EC’s equally (1).

With the normal physiology of the cardiovascular system containing a perfect balance of shear stress, it is the changes in shear stress on endothelial cells that are brought on by changes in flow and pressure (due to plaques or other issues) that can give rise to complications.

  The aggravation of a blood vessel by shear stress(3)

  CARDIOVASCULAR COMPLICATIONS

With obesity, hyperglycemia, and smoking being the leading cause of cardiovascular attacks, and with cardiovascular diseases being the leading cause of death, an analysis of endothelial cells is essential to medical research in this field (3). Cardiovascular diseases have cost the US almost 363.4 billion dollars from 2016-2017 (3). A key amount of the risks of cardiovascular diseases are associated with endothelium damage and are likely associated with the blood flow or locomotion-induced stresses of the body. Endothelial dysfunction “is associated with most forms of cardiovascular diseases, such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes, and chronic renal failure” (4). 

The severity of endothelial dysfunction is demonstrated by the life-threatening effects it can have on the cardiovascular system. One of these major health risks is hypertension. A study on obesity-associated hypertension says irregular blood pressure “…comes from studies showing that obese individuals display reduced capillary recruitment in response to reactive hyperemia and shear stress” (7). This furthers the point that shear stress on the endothelium has a strong impact on cardiovascular diseases.

UNDERSTANDING THE ENDOTHELIUM

Studying how and why endothelial cells function, and dysfunction, is crucial to understanding how to replicate their properties. Endothelial cells have several important functions in maintaining vascular homeostasis, however, its vascular permeability is the main function this study is attempting to mimic. The endothelial cells control the transfer of solute and macromolecules between the blood and the surrounding tissue (5). The transfer of small growth factor proteins, known as cytokines, occurs when there is endothelial dysfunction and a major factor in endothelial dysfunction is due to shear stress (6). An article that describes how growth factors affect blood vessels says, “Because hemodynamic factors provide signals that modulate arterial growth, major changes in blood vessels and hemodynamic function are expected” (8). They go on to conclude that these serious structural changes to blood vessels are an extreme risk factor in the development of hypertension in the cardiovascular system. This research serves to replicate an open system demonstrating how dangerous cell-activated products, such as these cytokines, are transferred out and how they affect vascular homeostasis. 

POTENTIAL LIMITATIONS

The unpredictability and the lack of information in the field of cardiology have made it difficult to find the exact answers and cures for different cardiovascular diseases. However, research has been done to analyze shear and tensile stress on endothelial cells. Although testing and results have been successful, there were a handful of limitations, including socioeconomic dilemmas. To start, the design for a closed system perfusion chamber includes a non-compact, large chamber, which can be inconvenient to experiment with (1). With our microfluidic chip design, the cost is minimal due to its size, simplicity in design, as well as compactness, and convenience.

END GOAL

With all these things in mind, it is clear the answer to cardiovascular treatment lies within the endothelial cells and examining the impact mechanical loads have on these EC’s could provide a lasting change in the world of medicine. Our compact and efficient design is one step towards the future of microfluidics and cardiovascular disease research. As cardiovascular complications continue to run rampant in the world, research will continue to enhance and improve its efficiency.