Ramak Khosravi Receives Award For Work on Arterial Grafts

Ramak Khosravi, a graduate student in Biomedical Engineering, has received a Congenital Heart Defect Research Award (CHDRA) from The Children’s Heart Foundation and the American Heart Association. 

Khosravi received the award for her work in engineering arterial grafts from biodegradable polymers, with reduced costs and off-the-shelf availability. Over time, the grafts are to be replaced by the patient’s own cells when arteries and veins need replacement in children living with CHD. Her research program was one of five selected to receive a total of $561,798 in funding. She is in the lab of Jay Humphrey, John C. Malone Professor of Biomedical Engineering and Chair. 

Here’s an overview of Khosravi’s work:

The major problem being addressed by this study

Our research is aimed at creating a new replacement conduit for children and adults suffering from cardiovascular disease and requiring surgical intervention. Most of these patients do not have suitable arteries and veins to replace their diseased vessels. Currently used grafts are made of materials that do not degrade, lack growth potential, and are prone to complications. To overcome this, we are engineering arterial grafts from biodegradable polymers, with reduced costs and off-the-shelf availability, which will over time be replaced by the patient’s own cells. We can improve graft design using computer simulations and long-term studies in a mouse model to identify the optimal design for patients needing grafts for bypass procedures, hemodialysis, or repair of congenital heart defects.

The specific questions being asked, and how the study attempts to answer them

There has yet to be a formal attempt to optimize the design of polymeric scaffolds such that they have biomechanical properties closest to native arteries. We will begin by surgically implanting multiple scaffolds with different design features, and evaluate their performance in our mouse model. We will then evaluate which design features are critical for controlling the inflammatory response to the polymer, and identify the key cells and signaling molecules involved. Finally, we will use the data to develop and inform a computational model of arterial graft development that uniquely combines biochemistry and mechanics. Once validated, the model can be used to perform many time- and cost-efficient simulations and identify scaffold properties predicted to give optimal long-term outcomes.

Long-term biomedical significance of your work

Successful completion of this research will not only establish a new computational-experimental approach for arterial tissue engineering, but will also result in a significantly improved graft for use in the arterial circulation. This is critical for children and adults requiring surgical interventions for cardiovascular disease, which in the U.S alone is over 600,000 patients annually. Our grafts will be composed entirely of the patient’s own cells, available off-the-shelf, and greatly reduced in cost. They can be fabricated with properties that ensure patient specificity, such as growth capacity in children and compliance matching and mechanical strength in adult patients. Computational predictions may also guide appropriate pharmacological therapies following graft implantation.

In 2014, the AHA and the CHF established the Congenital Heart Defect Research Awards to fund $2.5 million in CHD research grants from 2014 through 2016. In November 2015, the organizations expanded their collaborative funding project, earmarking an additional $20 million for CHD research over the course of five years.  An estimated minimum of 40,000 infants are expected to be affected by congenital heart defects each year in the United States. About 25% of babies born in the U.S. with a congenital heart defect require invasive treatment in the first year of life. Research that helps understand, identify and treat congenital heart defects is helping these children live longer and healthier lives – since 1979, deaths from CHDs in the United States have declined by 39%.