From Printer to Patient

October 20, 2015

By Alla Katsnelson

The human heart is an engineering marvel. A two-sided pump, it coordinates the flow of blood into the lungs to pick up oxygen, and then out into the body to deliver it. In adults, the heart pumps 1.5 gallons of blood each minute and 1.5 million gallons over a lifetime. But in rare cases, babies are born with hearts so malformed and the vessels within them so abnormally routed that they cannot properly pump blood at all. Confronting such tough cases, surgeons like Emile Bacha, MD, director of congenital and pediatric cardiac surgery at NewYork-Presbyterian Congenital Heart Center, have two options: Repair the baby’s heart by enlarging narrowed areas, closing errant holes, and realigning vessels, or conduct a palliative operation known as a Fontan procedure that leaves the infant with muchreduced heart function. The trouble is, a baby’s heart is difficult to image and the convolutions inside this pingpong ball-sized structure add to the complication. “You pretty much have to figure it out on the table,” Dr. Bacha says. When you do not know what you are getting into before you start, he adds, the chance for achieving a full repair is lessened.

Last summer, pediatric cardiologist Anjali Chelliah, MD, assistant professor of pediatrics, brought just such a case to Dr. Bacha, the Calvin F. Barber Professor of Surgery. Her patient, still unborn at 35 weeks of gestation, had a rare form of a congenital heart malformation called double outlet right ventricle. Based on the maze of holes and abnormally connected vessels within, Dr. Bacha doubted that he would be able to fully repair the baby boy’s heart.

Dr. Chelliah came bearing a solution, however: What if they could use a 3-D printer to generate a perfect model so that Dr. Bacha could literally hold the infant’s heart in his hand, study its ins and outs, make some test cuts, and design a clear plan for the procedure before the baby entered the operating room? That prospect could revolutionize the outcome for these babies, Dr. Bacha says. “The technology is such an obvious marriage with what we need.”

3-D printing—essentially printing with a solid substance rather than with ink to generate an object you can hold in your hand—is not a new technology. Invented in 1983, it was initially embraced by industrial designers as a bold, quick way to prototype new ideas. But it was not long until researchers began to explore its promise in medical applications. Today, 3-D printing has spread so widely that anyone can buy a basic device on for less than $1,000. Meanwhile, biomedical researchers are using ever more sophisticated printers to address clinical needs, devising ways to print everything from custom-made blood vessels and bone segments to scaffolds that release proteins and hormones to boost the body’s own regenerative potential. The beauty is that these materials can be custom-formulated to address the distinct needs of a specific individual. “All of this is part of the overall movement toward personalized medicine,” says Dr. Chelliah.

Dr. Chelliah first saw the benefits of using 3-D printed models in pediatric cardiac interventions during her fellowship at the Children’s National Medical Center in Washington, D.C., and she was excited to bring the technique to P&S when she joined the faculty in 2013. “Columbia has a larger-than-usual pediatric congenital heart disease patient volume as well as a pretty complex mix of patients,” she says. “I thought it would be a very exciting project to bring here.”

Dr. Chelliah’s timing was fortuitous: Not long after her arrival at Columbia Marie Hatcher, president and founder of Matthew’s Hearts of Hope, a foundation for children with congenital heart defects, decided to offer small research grants to pediatric cardiology fellows. Ms. Hatcher’s son, Matthew, now 7 years old, was born with double outlet right ventricle and had already had three surgeries. When Ms. Hatcher received an application for a $5,000 grant from Dr. Chelliah’s colleague, then pediatric cardiology fellow Hannah Fraint, MD, to use a novel 3-D technique to create a model in advance of surgery, Ms. Hatcher and the board members reviewing the applications gave it top marks for potential impact for a modest sum.

With the funding in hand, it did not take long for Dr. Fraint and Dr. Chelliah to identify the unborn boy with the maze for a heart as a clear candidate for the procedure. His congenital heart malformation had been diagnosed five months into gestation at a different facility and when his parents came to Dr. Chelliah, a fetal cardiogram revealed just how complex his heart anatomy was.

Having identified their first patient, the team turned its attention to obtaining the most precise possible 3-D image of the infant’s heart. To get it, Dr. Chelliah partnered with cardiologist Andrew Einstein, MD, associate professor of medicine (in radiology) and director of cardiac CT research. A number of imaging techniques exist that can shed light on the shape—or the mis-shape—of a baby’s heart. Echocardiography and cardiac MRI provide a complete enough picture in many cases, but cardiac computed tomography is often the best modality for visualizing cross-sections of the 3-D relationships among cardiac structures. Yet doctors generally hesitate to use cardiac CT in children so young, says Dr. Einstein, because it essentially involves taking a series of X-rays, thus exposing young patients to potentially dangerous doses of radiation.

Over the past year, Dr. Einstein and Dr. Chelliah have developed a protocol for cardiac CT in babies that uses lower-energy X-rays and fewer of them, localized to as small an area as possible, effectively reducing the radiation dose to the equivalent of afew chest films. “I don’t know of anyone doing CT scans of the heart with doses as low as we’ve been able to do, in the smallest children,” says Dr. Einstein. The duo’s first effort to scan Dr. Chelliah’s patient, on the day he was born at 39 weeks’ gestation, didn’t go well; the baby was moving and crying too much. “We brought him back on day two and repeated the scan with general anesthesia,” says Dr. Einstein. “I had no worries about repeating the scan and the second time worked like a charm.”

As the baby lay in Morgan Stanley’s neonatal intensive care unit, receiving a continuous infusion of medication to keep his aorta open, his cardiac CT data traveled to the offices of a small Belgian 3-D printing company called Materialise to be turned into a tiny clear plastic replica of his heart. Two days later, Dr. Bacha had a model in hand. “For us, these complex cases have always been high stakes, high drama; only the best surgeons did them because you had to think on your feet and make the right decisions quickly,” says Dr. Bacha. “Having practiced for the last 18 years under this kind of pressure, I appreciate being able to look at [the heart] at my leisure.”

When the baby was a week old, Dr. Bacha was able to perform a complete repair in a surgery that lasted less than six hours, averting what otherwise would have been three procedures spread over the next three years. After 10 days of recovery, the infant was able to go home to his family. “We don’t anticipate that this baby is ever going to need another surgery,” Dr. Chelliah says.

One of the most heartwarming features of the baby’s case, Dr. Chelliah says, is how grateful the baby’s parents were for the piece of plastic that had so drastically changed their son’s prognosis. Just a few days before the infant’s family was able to take him home, Dr. Chelliah and Dr. Fraint learned that Marie Hatcher and her son, Matthew, were in the hospital. With the moms’ permission, the two pediatric cardiologists arranged to have the families meet. Ms. Hatcher recalls making her way to the NICU to find the baby’s mom standing over an infant who, with his dark hair and round face, looked uncannily like her own son had at that age. After the mothers embraced, the baby’s parents got a chance to meet Matthew and thank him for what he does to help other babies.

“Matthew went through three surgeries,” says Ms. Hatcher. “Knowing that another mom’s baby was only going to have to go through one was huge. You know you’re doing good work but when you actually see that person and their baby and you know that you have had a big impact on their lives, it’s very humbling and very gratifying.”

Over the past year, four other young patients have had surgeries. The first was a 4-year-old girl who underwent two palliative surgeries shortly after her birth and on whom Dr. Bacha too managed to do a complete repair. Following her, a 4-year-old, a 5-month-old, and a 3-year-old—all of whom had already undergone at least one palliative surgery—also received a complete repair.

Although the Matthew’s Hearts of Hope pilot study has ended, Dr. Chelliah has secured additional funding to extend the 3-D work and the doctors are hoping to join two upcoming multicenter trials to collect further data. “We want to show that this really does have a major impact,” she says. “Anything that can help pediatric patients avoid multiple surgeries is obviously not just beneficial for them, but should persuade insurers to cover it as well.”

She and her colleagues are convinced that the procedure will soon become routine. They are also exploring other ways that the technology could be leveraged. “This is just where we chose to start,” Dr. Chelliah says. “We know it can be applied in many, many kinds of patients.”

Jeremy Mao, DDS, PhD, the Edwin S. Robinson Professor of Dentistry (in Orthopedic Surgery), has devoted much of his research career to the meniscus, a C-shaped piece of cartilage in the knee. As with other tissues comprised of fibrochondrocytes—present only in the spine and in places where tendons connect to bone—the meniscus heals poorly. Dr. Mao and his team identified the protein cues that push stem cells to differentiate into fibrochondrocytes, then used a 3-D printer to produce custom-tailored, meniscus-shaped bioscaffolds loaded with the proteins to implant in animals. “In just about all the ways we look at this, the regenerated meniscuses were similar to the native ones,” says Dr. Mao, who hopes to start human testing in the next year.

Dr. Mao believes this work just barely scratches the surface of the potential for 3-D printing to improve patients’ lives. He is collaborating with Michael Shen, PhD, professor of medical sciences (in medicine), of genetics & development, and of urological sciences (in urology), to print 3-D hydrogels that model the niche in which cancer cells live. The most obvious applications, however, lie in the field of regenerative medicine. Michael Kazim, MD, clinical professor of ophthalmology and of surgery, has recreated the orbital structure of the eye, an application for which the materials currently used are outdated and not biocompatible. Francis Lee, MD, theRobert E. Carroll and Jane Chace Carroll Laboratories Professor of Orthopedic Surgery, is testing simple 3-D implants to correct bone defects.

While research continues to identify other uses for 3-D printing in health care, Dr. Einstein, whose expertise in cardiac CT was vital for the Matthew’s Hearts of Hope pediatric patients, has started to examine the possibility of creating high-precision models for adult heart patients, such as those who have atrial fibrillation. And much more can be done for the youngest critically ill cardiac patients, as well, says Dr. Chelliah. “A major problem in pediatrics is that it is hard to get devices made in pediatric sizes,” she says. “There just aren’t that many children who need them, and children are variable sizes while adults are closer to one size.” To stent a child’s heart, for example, cardiologists often use liver stents created for adults. Says Dr. Chelliah: “We see a world where, a few years from now, when we see a patient with a hole in his or her heart, we will be able to visualize it and maybe even print a device that will go into the child’s heart, sized exactly as needed.”

Read more about Dr. Mao's work.