As a participant in the Roy and Diana Vagelos Scholars Program in the Molecular Life Sciences at the University of Pennsylvania, senior Chris Kampmeyer has spent the past year testing the shapes of coronary stent struts.
“I’m interested in finding applications of biochemistry in the broadest sense, a goal which influenced my decision to pursue work in cardiovascular research,” Kampmeyer, from Harleysville, Pa., says.
His research concentrates on cardiovascular stents, mesh tubes that are inserted to open obstructed blood vessels. He explains that patients suffering from angina, or chest pain, often opt for stents in order to increase blood flow in arteries narrowed by atherosclerosis.
But stent insertion can lead to complications or cause more serious conditions: Patients can experience re-closing of arteries due to restenosis, proliferation and migration of smooth muscle cells, or thrombosis, the formation of blood clots.
Kampmeyer works with Juan M. Jiménez, research associate in Penn’s Perelman School of Medicine, who explains that pharmaceutical companies have attempted to eliminate these problems but have failed to focus on the underlying hemodynamics of stent design.
“Drug-eluting stents deploy drugs that address the natural healing process and stop all cell types from migrating and dividing,” Jiménez says. “But the problem is that you now have an environment ripe for blood clots to form in the vessel.”
In order to find a different solution, Kampmeyer and Jiménez have turned to blood flow and the actual cross-sectional geometry of the stent strut, a protrusion of the stent that lines the vessel wall.
“Our hypothesis is that the geometry of the stent strut itself is correlated with how blood clots form,” Kampmeyer says.
Kampmeyer explains that current commercial stents have rectangular cross sections, which can form recirculation zones. In turn, these zones allow activated platelets, red blood cells and other blood molecules to accumulate, all of which propagate thrombus formation.
“We believe that a more streamlined geometry could prevent thrombus formation by reducing the size of the recirculation zones,” Kampmeyer says.
To achieve these streamlined stents, Jiménez notes that the lab is utilizing fluid dynamic concepts in the design of stent struts.
“What we have proposed is to bring aerodynamic principles and introduce them into the design of stent struts,” Jiménez says.
Kampmeyer has tested this theory with two different stent strut geometries, circular arc and rectangular. He works specifically with fibrin, a protein that crosslinks with itself to create a web-like structure that forms blood clots and thus contributes to in-stent thrombus formation.
After a number of experiments measuring fibrin deposition in the vicinity of multiple stent strut geometries, by use of a blood substitute and silicon stent models, Kampmeyer says his lab has concluded that the shape of the stent strut does affect fibrin deposition and thrombus formation.
“We’ve found that by simply changing the stent strut geometry, you can locally change the blood flow and significantly reduce the amount of fibrin deposition,” Jiménez says.
The lab is currently conducting similar experiments, with human blood.
Kampmeyer hopes these efforts will lead to the adoption of a safer, more streamlined stent that reduces health risks for coronary artery disease patients.
“Stent implantations are becoming more and more popular and, in order to prevent them from causing problems for patients in the future, we need to alter the stent strut design,” Kampmeyer says.
The Vagelos Scholars program, an enhanced version of the biochemistry major, was established in 1997 by Roy Vagelos, a Penn graduate and former chief executive officer of Merck pharmaceutical company.
The program promotes a foundation in chemistry, mathematics and physics, and scholars have the option to pursue a double major in two sciences or a major in chemistry or biochemistry with a submatriculated master’s degree in the same field.
“The purpose of Vagelos Molecular is to send Penn undergraduates to the very best science or applied science graduate schools,” explains Ponzy Lu, program head and professor of chemistry.
Scholars are also required to complete two paid summer research projects on campus. A biochemistry major, Kampmeyer has worked since 2012 in Penn's Institute for Medicine and Engineering in the lab led by Peter F. Davies, professor of cardiovascular medicine.