A New Treatment That Clicks for Aortic Aneurysms
Vorp Lab and collaborators receive $750,000 Collaborative Sciences Award from AHA
Abnormal aortic aneurysms (AAA) affect around 200,000 patients in the U.S. every year. Surgery is currently the primary treatment, but some patients who are diagnosed early with AAA often find themselves unwillingly waiting for the aneurysm to get worse before surgery is an option.
Researchers at the University of Pittsburgh Swanson School of Engineering recently received a competitive award from the American Heart Association (AHA) for research that hopes to provide early, minimally invasive treatment for these types of aneurysms.
Senior Associate Dean for Research & Facilities and Professor of Bioengineering David Vorp and his team in his Vascular Bioengineering Laboratory will collaborate with Carnegie Mellon and Vanderbilt University on the project, “Clickable Extracellular Vesicles for Aneurysm Stabilization,” which won the AHA’s Collaborative Sciences Award.
At Pitt, Vorp’s lab focuses on vascular biomechanics and regenerative medicine. In the winning research proposal, the team focused on preventing AAA, which occurs when the aorta degrades and balloons into a larger size than normal, putting patients at risk of rupture and hemorrhage.
Vorp and his team collaborated with Carnegie Mellon University Biomedical Engineering Professors Charlie Ren and Phil Campbell to use “click chemistry”, a Nobel-prize winning molecular bonding technique that enables molecules to quickly and effectively snap together. In addition, the team will use mouse models from Vanderbilt University Vascular Surgery Professor John Curci to test their theories along the way.
Click chemistry, referring to chemical reactions with high selectivity, high yield, and fast reaction rate, will enable the team to bind extracellular vesicles to a material for minimally invasive delivery to the aneurysm wall. According to Ande Marini, a PhD student working on the project, interventions for AAA are typically surgical, so the team looked to other less invasive methods to prevent AAA enlargement to a dangerously critical size.
“We're really interested in this disease because there's only the option of surgical intervention right now, either open surgery or endovascular repair, and it's really only offered for patients who have an expansion of their aorta that's above five or 5.5 centimeters,” Marini said. “There is a waiting period during expansion where patients and their surgeons are just watching and waiting as their aorta expands.”
Factors such as aging and co-existing conditions such as diabetes further complicate aneurysm surgery, so to avoid it altogether, Marini said that the project will focus on using extracellular vesicles (EVs) to send regenerative signals to the aorta.
“These extracellular vesicles are isolated from mesenchymal stem cells,” Marini said. “EVs are neatly packaged signals that cells send to each other to communicate, and they act as the mailmen between cells.”
Once EVs have been isolated, the next step is to find a way to send them to the aorta and keep them there. To do so, the team will utilize the click chemistry capabilities from their CMU collaborators to attach the EVs to a material that can be safely delivered.
“Because they are click-bound to the material, the EVs will stay where they can have the desired effect. They are localized to that specific area of interest and not going everywhere else in the body.” Marini said.
According to Vorp, who is the primary investigator, the team hopes that using this approach will send regenerative signals to prevent further degradation of the aorta and keep the treatment localized to the aorta itself.
“If we could find a way to attach EVs to suitable materials, then applying that material to the outside of the aneurysm is a potential way to localize them and use only what is needed,” Vorp said. “First, EVs are pretty valuable and we don't want to waste them, and second we don't want them to go somewhere else and have undesired, off target effects.”
The Collaborative Sciences Award will support this project for three years and provide $250,000 in funding each year, or $750,000 total.
“I think it's really novel and great to use this click chemistry that's coming into the spotlight and getting ahead of the curve before too many people start going down that route,” Marini said. “It's really cool to use that with EVs, which are also just emerging as therapeutics.”