University of California, San Diego
Mechanical and Aerospace Engineering
MAE 156B: Senior Design Project
Background
Pulmonary Arterial Hypertension (PAH) is a life-threatening condition characterized by high blood pressure in the arteries of the lungs(Figure 1), often resulting from congenital heart defects. This condition leads to reduced oxygen flow, heart strain, and, ultimately, a shortened lifespan, especially in infants and children.To better understand the biomechanical forces (Figure 2) affecting vascular cells in PAH, researchers at the UCSD Experimental Biofluidics Lab are investigating how shear stress, normal stress, and cyclic stretching influence endothelial cell(Figure 2) behavior and gene expression.Existing research equipment can apply shear stress and cyclic pressure separately(Figure 2), but no current device can simultaneously apply and measure all three forces within a single system. The Enclosed Cell Stretcher 2.0 aims to fill this gap by integrating controlled shear flow, cyclic stretching, and pressure application into one enclosed system.With this device, researchers can study how endothelial cells react to mechanical forces in a controlled, biologically relevant environment, contributing to advancements in vascular disease treatment and potential new therapeutic approaches for PAH.
Figure 1. Diagram of heart and left lung [1]
Figure 2. forces acting on the endothelium of an artery. [2]
Figure 3. Appearance of a healthy artery compared to narrowed arteries [1]
Objectives
The Enclosed Cell Stretcher 2.0 was developed to improve upon previous research devices (Figures 4,5) by integrating shear stress, cyclic stretching, and pressure regulation into a single enclosed system. This will enable more accurate and efficient studies on endothelial cell behavior, particularly in relation to Pulmonary Arterial Hypertension (PAH).
Previous designs allowed researchers to apply shear stress and cyclic pressure independently (Figures 4,5), but no existing system could simultaneously apply and measure all three mechanical forces in a biologically relevant manner. Our project aimed to fill this gap by refining and expanding the capabilities of last year’s cell stretcher design (Figures 4,5).
By achieving these objectives, the Enclosed Cell Stretcher 2.0 provides researchers with a versatile, user-friendly platform to study vascular cell responses under real-world biomechanical conditions (Figure 2), ultimately contributing to advancements in PAH research and potential new treatment strategies.
Figure 4. CAD model of previous design
Figure 5. Real life previous design
Design Requirements:
Apply and regulate mechanical forces on endothelial cells
Shear stress: 0.2 - 5 Pa (2-50 dynes/cm²)
Cyclic stretching: 0-20% uniaxial deformation at 1-2 Hz
Pressure: 0.67 - 9.33 kPa (5-70 mmHg)
Implement a pneumatic actuation system for smoother and more controlled membrane stretching
Ensure uniform Hele-Shaw flow while minimizing disturbances from membrane movement
Use biocompatible, sterilizable materials for safe and repeatable experiments
Develop an Arduino-based control system to monitor and adjust pressure, flow, and stretching
Design Desirements:
Improve experimental consistency with precise pressure and stretch control
Make the system modular for easy cleaning and maintenance
The final design solution was focused on developing a device that can conduct pneumatic stretching. The device had four main components: an enclosure of all the components, false walls, a membrane, and a pressure chamber. The pressure chambers were connected to a vacuum line in order to induce stretching. The false walls were connected to the lid of the enclosure in order to create a pivot that the membrane could stretch around. The membrane itself was placed between the lid of the enclosure and the pressure chambers. The false walls and pressure chambers were both 3D printed out of ABS (Acrylonitrile Butadiene Styrene). Compared to PLA (Polylactic Acid), ABS is a water resistant material that can be submerged without damaging the part. The area between the false walls and the membrane creates a 1 mm channel where water will flow over the endothelial cells.
Figure 6. CAD of final design.
Figure 7. Exploded view of CAD of the final design. This CAD only depicts the lid of the enclosure.
Figure 8. X-axis deformation of Membrane in ANSYS simulation showing how the devise stretches the membrane.
Figure 9a. Reference points
Figure 9b. Reference points w/ ROIs
Figure 9c. Reference Points w/ ROIs during max displacement
We used a custom MATLAB script to draw ROIs around points and calculate strain using pre-stretching and post-stretching images.
References
Parkway East Hospital. (n.d.). Pulmonary Arterial Hypertension. Parkway East Hospital. https://www.parkwayeast.com.sg/conditions-diseases/pulmonary-arterial-hypertension/symptoms-causes
Zhou, J., Lim, S.H. & Chiu, JJ. Epigenetic Regulation of Vascular Endothelial Biology/Pathobiology and Response to Fluid Shear Stress. Cel. Mol. Bioeng. 4, 560–578 (2011). https://doi.org/10.1007/s12195-011-0199-2