University of Texas Arlington Bioengineering Associate Professor Kytai Truong Nguyen has received a four-year, $1.4 million National Institutes of Health grant to create a nanoparticle system to shore up arterial walls following angioplasty and stenting procedures to treat coronary arterial disease.
Dr. Nguyen explains in a UTA release that the research looks to improve an established procedure like angioplasty, which opens arteries and blood vessels that are blocked. Her co-principal investigator in this funded NIH research is Penn State University associate professor of biomedical engineering Jian Yang — a former UT Arlington bioengineering associate professor. Drs. Nguyen and Yang recently received funding from the National Institutes of Health on a project to develop nanoparticles that mimic the platelet in the blood that forms the clot and create a cover over the damage to promote healing in damaged endothelium, the lining of blood vessels, which can be injured in surgical procedures that unblock clogged arteries.
“Angioplasty and stenting often damage arterial walls,” Dr. Yang explains in a Penn State release, “with a significant risk of subsequent complications, such as re-narrowing of the artery or blood clot.” Platelets accumulate on the damaged vessel, initiating clot formation. Other cells can deposit on the cell wall, building up a blockage. The result is multiple surgeries and multiple stent replacements. “We have discovered a way to use nanoparticles to help the arteries heal themselves more effectively following one of the most common surgical procedures,” says Dr. Nguyen, who joined UT Arlington in 2005. “This process promises to reduce complications that can occur in the arteries following surgery and may extend opportunities for patients to live longer, healthier lives.”
A paper published in December, 2013 in the journal Acta Biomaterialia, entitled “Dual growth factor releasing multi-functional nanofibers for wound healing,” (http://dx.doi.org/10.1016/j.actbio.2013.07.030 Acta Biomaterialia Volume 9, Issue 12, December 2013, Pages 9351–9359), co-authored by Drs. Nguyen and Yang with colleagues Zhiwei Xie, Christian B. Paras, Hong Weng, Primana Punnakitikashem, Lee-Chun Su, Khanh Vu, and UTA Bioengineering Department professor and interim chair of the http://www.uta.edu/bioengineering/<a href=”http://www.uta.edu/utamagazine/2012/07/liping-tang-2/”>Liping Tang</a>, notes that the research objective of this is to develop a dual growth factor-releasing nanoparticle-in-nanofiber system for wound healing applications. In order to mimic and promote the natural healing procedure, chitosan and poly(ethylene oxide) were electrospun into nanofibrous meshes as mimics of extracellular matrix. Vascular endothelial growth factor (VEGF) was loaded within nanofibers to promote angiogenesis in the short term. In addition, platelet-derived growth factor-BB (PDGF-BB) encapsulated poly(lactic-co-glycolic acid) nanoparticles were embedded inside nanofibers to generate a sustained release of PDGF-BB for accelerated tissue regeneration and remodeling. In vitro studies revealed that our nanofibrous composites delivered VEGF quickly and PDGF-BB in a relayed manner, supported fibroblast growth and exhibited anti-bacterial activities.
The researchers’ nanoparticle is decorated with a ligand called GP1b peptide that links to endothelial progenitor cells circulating in the blood that can grow into mature endothelial cells. Over time, the nanoparticles will degrade harmlessly as the new blood vessel lining repairs the damage, avoiding the need for a stent. “The surgeon will still do angioplasty first, but not put in a stent. Instead they will inject the nanoparticle solution, if necessary more than once,” Dr. Yang explains in the Penn State release. “Our nanoparticles have two functions: They will serve as a temporary template to cover injured vascular wall to prevent the underlying smooth muscle cells’ over growth inward to block the artery. Once the nanoparticles attach to the vessel wall the platelets cannot attach. Then the nanoparticles will catch the circulating endothelial progenitor cells to form a healthy endothelium on the injured vascular wall. Once the missions are done, the nanoparticles will simply disappear without causing any long-term toxicity. These injectable nanoparticles have worked well in animal models in studies with our collaborators at UT Arlington.” The team received $1.4 million over four years from the National Institutes of Health to develop this technology.
According to the Centers for Disease Control and Prevention, nearly 1 million people in the United States have angioplasty or stent procedures done annually.
Khosrow Behbehani, dean of the College of Engineering, says Dr. Nguyen is specializing in developing innovative techniques for drug delivery which are critical to advancing health care.
“Earning a National Institutes of Health grant puts Dr. Nguyen in very exclusive company,” Dr. Behbehani notes. The NIH reported that only 16.8 percent of its nearly 50,000 applications in 2013 were awarded grants. “Receiving this grant reflects the cutting-edge research that Dr. Nguyen is conducting. Her investigation will help improve the efficacy of stents in treating cardiovascular anomalies.”
Following the angioplasty or stent, surgeons would insert the nanoparticles at the affected site, and the nanoparticles would attach themselves to the arterial wall. The nanoparticles would be programmed to recruit stem cells, which would regenerate the arterial wall’s weakened cells naturally, Dr. Nguyen says. Then once cell regeneration is well under way, the nanoparticles will dissipate. The process addresses concerns that arise when a person’s underlying smooth muscle cells migrate to the weakened arterial walls and the blood cells attack this damaged site.
“Your body naturally will send smooth muscle cells to the weakened walls,” explains Dr. Nguyen. “That creates a whole host of problems the body doesn’t need. It could cause re-narrowing of an artery, leading to a heart attack.”
Research collaborator Dr. Liping Tang says Dr. Nguyen’s work makes the surgery safer for the patient. “Using nanotechnology to solve the problem before it even occurs is ingenious,” Dr. Tang observes in the UTA release.
Dr. Nguyen previously received an American Heart Association grant to study how physical and biological factors influence the proliferation of vascular smooth muscle cells, a condition that can lead to heart disease, and recently also received another American Heart Association grant to develop advanced particle scaffolds for treatments of peripheral arterial disease. She also has teamed with a UT Southwestern colleague to develop a nanoparticle drug delivery system that will help stimulate lung growth and function after partial lung removal or destructive lung disease.
Dr. Nguyen’s other collaborators are Dr. Tang and Subhash Banerjee, an associate professor of medicine and co-director of the Cardiac Catheterization Laboratories at UT Southwestern Medical Center at Dallas and VA North Texas Health Care System at Dallas who is a nationally and internationally recognized expert in the field of interventional cardiology.
The University of Texas at Arlington is the second largest institution in The University of Texas System, with total research expenditures reaching almost $78 million last year. UT Arlington ranks fifth in the nation for undergraduate diversity and was ranked as the seventh fastest-growing public research university by The Chronicle of Higher Education in 2013.
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