An undergraduate student developed and tested several bioresorbable and radiopaque arteriovenous grafts to be used to improve dialysis access. Failure of arteriovenous graft placement for patients on dialysis can lead to neointimal hyperplasia (NIH), which can cause narrowing of the blood vessels.
Sarah Honegger, a senior at the University of Notre Dame, was selected by her college to spend 10 weeks in summer 2022 as a research student in the MD Anderson Cancer Center lab of Marites Melancon, PhD, associate professor in the department of interventional radiology.
Ms. Honegger will present her Featured Abstract “Bismuth Nanoparticle and Dipyridamole-Loaded Electrospun Polymeric Scaffold as Radiopaque Bioresorbable Drug-Eluting Vascular Graft” during Sunday’s Scientific Session 3, Dialysis Interventions and Management, Room 222AB of the Phoenix Convention Center.
“The special part of these vascular grafts is that they have bismuth nanoparticles,” Ms. Honegger explained. “We also chose to incorporate a drug called dipyridamole, or DPA, into these grafts that acts as a vasodilator and antiplatelet to prevent some of the issues that can sometimes occur when you implant a vascular graft into a person.”
Antiplatelet and vasodilator drugs mitigate NIH and long-term patency post graft placement. Nanoparticles allow for visualization and long-term monitoring of these absorbable medical devices.
The research team aimed to develop a bioresorbable and radiopaque bismuth nanoparticle (BiNP) and DPA-loaded scaffold made of polycaprolactone (PCL) and polyethylene glycol (PEG).
Ms. Honegger first learned the electrospinning process to fabricate the grafts. “I then proceeded to run a bunch of different in vitro tests to analyze how this worked, how the particles would be released from the grafts, and what kind of radiopacity you would see under CT and X-ray,” she said. “We also looked at some cell toxicity to make sure that the grafts wouldn’t be harming the cells once implanted.”
Solutions of nanoparticles PCL, PEG, BiNP and DPA were electrospun into 3-cm scaffolds, which were monitored over 6 weeks in terms of drug and nanoparticle released, tensile strength and radiopacity. In vitro hemolysis and cytotoxicity assays were done to test biocompatibility of grafts.
The findings showed that DPA-loaded grafts released approximately 38 percent of the drug over 7 days, which increased to about 70 percent over 12 weeks. BiNP-loaded grafts released between 3 and 5 percent of the total BiNP within the first 12 weeks, which correlated with a radiopacity loss of only 16.6 percent over the 12-week trial period.
The results showed that trilayer scaffolds made of PCL and PEG and loaded with both DPA and BiNP demonstrated increased radiopacity. There were no detrimental effects on epithelial or vascular smooth muscle cells, and there was an effective release of DPA over time.
Ms. Honegger’s successful in vitro work allowed Dr. Melancon’s lab to move on to rat models to study imaging and efficacy.
Dr. Melancon said her team is still in the process of optimizing the best materials. “I think we can still do a little bit of tweaking in terms of the polymers and therapeutic agents we use, for example, using mesenchymal stem cells instead of the drug,” Dr. Melancon said. “After our in vivo work on rats, we plan to test this technology in large animal models and potentially look at some commercialization prospects for our project.”
