Help for Young Hearts
As a young student shadowing pediatric oncologists, Elizabeth “Libby” Stephens realized just how hard it is to be around children who are ill. It was all the prompting she needed to try to get to the heart of the matter.
The San Diego native, working on combined medical and bioengineering doctorates at Rice and the Baylor College of Medicine, has received a fellowship from the National Institutes of Health to pursue her research into the development of replacement heart valves for young patients that will grow as they do.
Currently, bad heart valves can be replaced in one of two ways: with a bioprosthetic valve (harvested from a pig, for instance) or with a mechanical device. Both methods have problems when used in children. Mechanical valves work well in adults but require anticoagulant medicine to thin the blood, and anticoagulants present potential dangers to active children prone to cuts. Bioprosthetic valves, which perform relatively successfully in adults, rapidly calcify in children. And there is an even more basic problem with both these treatments: Replacement valves don’t grow with the child, so they have to be replaced every few years, at the cost and discomfort of repeated open-heart surgeries.
Heart valves are complex connective tissues that evolve throughout a human’s life. Their compliance and stiffness, as well as their biology, change substantially with age, so figuring out how to make a valve that’s appropriate for a patient of a particular age will be tricky.
Congenital heart disease, which is found in 1 percent of newborns, is relatively easy to diagnose. “The valves are very disorganized,” Stephens said. “There are none of the layers, none of the properly aligned collagen — the connective tissue that gives tensile strength — that you’d expect to find.”
The main challenge is to find a way to make replacement valves that can be implanted once and for all, and Stephens is working to learn how to grow a new valve using the youngster’s own cells as the source material. To do that, she has called not only on her own medical and bioengineering skills, but also on those of her advisers, Jane Grande-Allen, an assistant professor of bioengineering, and Jennifer West, the Isabel C. Cameron Professor and chair of the Department of Bioengineering.
Stephens’ data will serve as a template for the process of building heart valves. “People have been collecting information on valves for a long time, but not with the resolution Libby hopes to achieve,” Grande-Allen said. “This fellowship gives her the opportunity to build on the research she’s already done.”
Heart valves are complex connective tissues, Stephens explained, that evolve throughout a human’s life. Their compliance and stiffness, as well as their biology, change substantially with age, so figuring out how to make a valve that’s appropriate for a patient of a particular age will be tricky.
Growing new valves involves both biochemical engineering to create the valve and mechanical engineering to build the device that will be used to grow it. Stephens said the biochemical part involves using a polyethylene glycol hydrogel, a water-insoluble polymer that can be used as the scaffold in which target cells drawn from the patient are suspended. The design of this hydrogel is the component being addressed by her research.
The mechanical part, the bioreactor, would contain the scaffold. “A bioreactor basically pumps media, the equivalent of blood, back and forth around the hydrogel while putting it through a bending motion that causes the cells to produce more collagen and extracellular matrix, making it stronger. Finally, when the valve is fully developed, surgeons will be able to implant it.” Several bioreactors are being designed by other graduate students in Grande-Allen’s lab.