Jonathan Butcher investigates the role of mechanical forces in the regulation of heart valve development and disease.
Heart valves, responsible for keeping blood flowing in one direction, stress the heart when they don’t work properly. Just half a millimeter thick, heart valves are translucent but incredibly tough, withstanding a barrage of forces with every beat of the heart. “We don’t have a good material that can replicate this. We don’t even know how these cells can withstand these forces and yet fix the tissue all the time,” says Butcher. “It’s essentially like there’s an onsite construction crew repairing damage as it happens.”
Babies born with heart defects, about one percent of all births, often require complicated surgery and a lifetime of medications—if they survive. “They are born with anything ranging from small holes between two chambers to entire chambers missing or rearranged,” says Butcher. “Some complicated heart defects are serious enough that pregnancy termination is often chosen over attempting repairs. I think we can do better for these babies, but it is going to take new technology and different ways of thinking.”
By studying how heart valves develop in chicken embryos, Butcher aims to drive advances in the diagnosis, repair, and replacement of heart valves. “We can use developmental biology to understand how a small insult can result at birth in a congenital defect that becomes a serious problem,” he says. “We try to attack this problem from an engineering perspective by mechanically changing the embryonic heart. You constrict a chamber with a suture, for example, or bore a hole between two chambers with a laser, and you begin to see patterns in how they develop in response to this. We can then relate these changes to the underlying biological processes. Eventually, we may be able to predict what will happen with a particular insult and perhaps how well an intervention might work.”
The synthetic replacements currently available fall far short of the real thing. “This is particularly important for children, because they grow and the non-living materials used now don’t, so you either have to put in a heart valve that’s too big and they grow into it, or you have to operate again later,” explains Butcher. “Plus it creates blood coagulation problems, so these kids have to take blood thinners for the rest of their life. Every knee scrape or finger cut is a potential life threatening problem.Not a good solution.”
The idea of growing a living heart valve from a patient’s own cells is appealing, but it has proved to be really challenging. Butcher believes his novel approach will get over the hump. “The idea is that from the embryo we would have the blueprint, understanding the sequence of stimulations that produces the final desired tissue,” says Butcher. “Nobody’s using developmental biology to innovate engineering strategies in this way. It is really not a ‘new’ idea if you think about it, but rather unlocking the ‘natural engineering’ process.”
Butcher chose Cornell as the place to practice his unique approach because of its up-and-coming Biomedical Engineering department and the prospect of collaborating with experts in other fields who could make the tools he needs. “Cornell was the best fit because there are people here that are world-class in areas I want to know more about, like laser optics and microfabrication,” he says. “I can improve and expand my own research here in ways I couldn’t do anywhere else.”
Prof. Butcher's Web site
