By Megan Christy, VI Form

Treating AAA (Abdominal Aortic Aneurysms)

I am captivated by one particularly compelling question: how can we manipulate the body so it fixes itself? Could a combination of biology, chemistry, physics, and engineering be the answer?

I began exploring this question in the summer of 2017 while participating in a biomedical engineering program at Boston Leadership Institute. There, I applied this question to the way in which we treat aneurysms. Abdominal aortic aneurysms (AAA) are a “silent killer.” They form when the walls of a blood vessel weaken and are difficult to diagnose due to the lack of symptoms prior to rupture.[1] Once ruptured, AAAs have a mortality rate of 90%.[2] When an unruptured AAA is diagnosed, it is vitally important to treat it in a minimally invasive and lasting manner.

There are two main treatment options for AAA: open surgery and endovascular aneurysm repair (EVAR). The surgical approach consists of removing the weakened section of the aorta and replacing it with a cloth tube. However, abdominal surgery is invasive, risky, and requires a long recovery time. The alternative to open surgery is EVAR, a procedure in which a stent graft is placed via a catheter where the aneurysm is located. The stent graft provides an alternative path for blood flow so the aneurysm does not grow and rupture. EVAR is preferable because it is minimally invasive, but it has a higher risk of rupture than open surgery. Currently, stent grafts have additional problems such as endoleaks and migration.

Multiple companies have made attempts to improve specific limitations of the stent graft: a stent graft with screws that secure the graft to the aortic wall,[3] a design with a more flexible metal support,[4] and another with two channels that allow the graft to extend to the bifurcated portions of the aorta.[5] Each of these solutions is an improvement but targets only one problem.

I see an opportunity to address all of these limitations and redesign the stent graft to provide a more permanent solution for abdominal aortic aneurysms – a biodegradable, regenerative stent graft. This stent graft would be minimally invasive and regrow the tissue in the walls of the aorta to provide a long-term solution. The stent graft would be coated with the patient’s own cells and a growth factor, then inserted into the aorta. The support in the stent graft would be temporary and eventually biodegrade, leaving only tissue as the cells regrow to become a new artery wall. My design addresses the major issues of endoleaks, movement, and rupture. I will continue to pursue this as the topic of my senior year STEM Fellowship research project.

Eager to begin my research, in the fall of 2017 I applied for the Class of 1968 Fifth Form Fellowship. This grant aims to “reward independent thinking, ingenuity, and planning and to encourage the student exploring non-traditional fields of inquiry or using non-traditional fields of investigation.” This grant provided me with the means to expand my understanding of medical device manufacturing in a professional environment. This summer I traveled to Burpee Medsystems, a stent manufacturing facility in New Jersey. Here I met the founder, Janet Burpee, and spoke with her about her experience as a metallurgist and medical device entrepreneur. I saw how her company makes stents as well as the machines her employees use to test device viability. I also traveled to Philadelphia where I met with Dr. Jeffrey Solomon, an invasive radiologist, who shared with me his experiences researching, designing, and deploying endovascular devices. I learned the fundamentals of stent design from these interviews. For example, Nitinol is the preferred metal used for stents because it is self-expanding, has shape memory, and is not hazardous to the body. Both Ms. Burpee and Dr. Solomon taught me the intricate method of making a stent, from forming the shape to sanding and shining it, as well as the lengthy FDA approval process that hampers the pace of medical device innovation. These experiences provided me with a strong foundation of materials science knowledge that I am applying to my research. The connections I made with these professionals spurred a series of interviews with other pioneers in the field and led to my introduction to Dr. Marsha Rolle, a professor of biomedical engineering at WPI, and Dr. Elazer Edelman, a cardiologist at Brigham and Women’s Hospital and professor at MIT. Dr. Rolle and Dr. Edelman will mentor me as I continue my research throughout my senior year.

This summer I also spent three weeks at an internship at the University of Pittsburgh Vascular Bioengineering Lab. This was a new program established between St. Mark’s and the renowned Starzl Transplantation Institute. This internship provided me with valuable hands-on lab experience that was closely connected to my STEM Fellowship project. At the University of Pittsburgh, I was mentored by Dr. Timothy Chung under the direction of Dr. David Vorp. My main project in the lab was to contribute to research on directed stem cell therapy of AAAs. AAAs form in a variety of sizes, and all are dangerous. Small aneurysms, however, are particularly difficult to treat because surgery is not recommended. These aneurysms must be closely monitored until they grow large enough for surgical intervention. Mesenchymal stem cell (MSC) therapy is a novel way to treat aneurysms of all sizes. MSCs are able to counteract the changes that occur in the extracellular matrix that cause aneurysms to form, thus halting aneurysm growth.

My research at the University of Pittsburgh aimed to identify ways in which clinicians can direct MSCs to target the aneurysm. I learned a wide array of lab techniques and procedures, but two tasks piqued my interest the most. First, I learned fluorescence microscopy and took images of rat aortic aneurysms. This started with cryosectioning the aorta to create slides, staining them and then observing them. Through the microscope, I located the aneurysm then filtered for stains of different colors to analyze the results of previous experiments. Next, I cultured mesenchymal stem cells that I used for experiments. Culturing cells was something I had no experience with, and it would be very difficult to try to learn on my own. With this experience of culturing cells in the lab with supervision, I now have the tools I need to do it again by myself. I head into my STEM Fellowship more confident and able to start my experiments earlier rather than spending time learning basic lab skills.

My lab experience was fascinating, but the talented professionals I met had the most significant impact on me. Teamwork was essential to their success, whether it was the collaboration between the mechanical and biological engineering sides of the lab or the emphasis on interdisciplinary learning. We cannot solve problems with just one perspective or just one person. I also observed the unique mentality of the people I interacted with; they were each tackling an unsolved problem head-on and undeterred. As I walked through the poster-filled halls to my lab, I was reminded daily of all the work my fellow researchers have done. The displayed projects, no matter how big or small the innovation, were one step forward in creating solutions to larger problems. This mentality motivates me to never see a challenge as too big. As I set up my lab this fall, reading articles and preparing experiments, I am eager to be a part of this inspiring community.

Megan Christy is a VI Form day student from Southborough, Massachusetts. She plays soccer, enjoys relaxing with her dogs, and loves to travel.

Footnotes

[1] “Aortic Aneurysms,” 2014

[2] A & C, 2009, p. 1

[3] Ohki, Deaton, & Condado, 2006/n.d., p. 1

[4] Geelkerken, Beuk, & Meerwaldt, 2016

[5] Hayes, 2017

References

A, A. N., & C, Z. K. (2009). Ruptured abdominal aortic aneurysm: a surgical emergency with many clinical presentations. Post Graduate Medical Journal, 85, 268-273. https://doi.org/10.1136/pgmj.2008.074666

Aortic Aneurysms: The Silent Killer. (2014, February 8). Retrieved March 27, 2018, from UNC Health Care website: https://healthtalk.unchealthcare.org/aneurysms-the-silent-killer/

Geelkerken, R. H., Beuk, R. J., & Meerwaldt, F. (2016). Anaconda™ AAA Stent Graft System for Challenging AAA Anatomy. Endovascular Today. Retrieved from https://evtoday.com/2016/11/supplement2/anaconda-aaa-stent-graft-system-for-challenging-aaa-anatomy/)

Hayes, P. (2017). Evolution Not Revolution: The Altura Stent Graft. Endovascular Today. Retrieved from https://evtoday.com/2017/03/evolution-not-revolution-the-altura-stent-graft/

Ohki, T., Deaton, D., & Condado, J. A. (n.d.). New Technology. In Endovascular Today [pdf]. Retrieved from https://evtoday.com/pdfs/EVT1106_01.pdf (Reprinted from Aptus Endovascular AAA Repair System, Endovascular Today, 29-36, 2006)