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ETH Zurich
ETH Zurich

This Soft Artificial Heart May One Day Shorten the Heart Transplant List

ETH Zurich
ETH Zurich

If the heart in the Functional Materials Laboratory at ETH Zurich University were in a patient in an operating room, its vital signs would not be good. In fact, it would be in heart failure. Thankfully, it's not in a patient—and it's not even real. This heart is made of silicone.

Suspended in a metal frame and connected by tubes to trays of water standing in for blood, the silicone heart pumps water at a beat per second—a serious athlete's resting heart rate—in an approximation of the circulatory system. One valve is leaking, dripping onto the grate below, and the water bins are jerry-rigged with duct tape. If left to finish out its life to the final heartbeat, it would last for about 3000 beats before it ruptured. That's about 30 minutes—not long enough to finish an episode of Grey's Anatomy

Nicolas Cohrs, a bioengineering Ph.D. student from the university, admits that the artificial heart is usually in better shape. The one he holds in his hands—identical to the first—feels like taut but pliable muscle, and is intact and dry. He'd hoped to demonstrate a new and improved version of the heart, but that one is temporarily lost, likely hiding in a box somewhere at the airport in Tallinn, Estonia, where the researchers recently attended a symposium.

Taking place over the past three years, the experimental research is a part of Zurich Heart, a project involving 17 researchers from multiple institutions, including ETH, the University of Zurich, University Hospital of Zurich, and the German Heart Institute in Berlin, which has the largest artificial heart program in Europe.

A BRIDGE TO TRANSPLANT—OR TO DEATH

Heart failure occurs when the heart cannot pump enough blood and oxygen to support the organs; common causes are coronary heart disease, high blood pressure, and diabetes. It's a global pandemic, threatening 26 million people worldwide every year. More than a quarter of them are in the U.S. alone, and the numbers are rising.

It's a life-threatening disease, but depending on the severity of the condition at the time of diagnosis, it's not necessarily an immediate death sentence. About half of the people in the U.S. diagnosed with the disease die within five years. Right now in the U.S., there are nearly 4000 people on the national heart transplant list, but they're a select few; it's estimated that upwards of 100,000 people need a new heart. Worldwide, demand for a new heart greatly outpaces supply, and many people die waiting for one.

That's why Cohrs, co-researcher Anastasios Petrou, and their colleagues are attempting to create an artificial heart modeled after each patient's own heart that would, ideally, last for the rest of a person's life.

Mechanical assistance devices for failing hearts exist, but they have serious limitations. Doctors treating heart failure have two options: a pump placed next to the heart, generally on the left side, that pumps the blood for the heart (what's known as a left ventricular assist device, or LVAD), or a total artificial heart (TAH). There have been a few total artificial hearts over the years, and at least four others are in development right now in Europe and the U.S. But only one currently has FDA approval and CE marking (allowing its use in European Union countries): the SynCardia total artificial heart. It debuted in the early '90s, and since has been implanted in nearly 1600 people worldwide.

While all implants come with side effects, especially when the immune system grows hostile toward a foreign object in the body, a common problem with existing total artificial hearts is that they're composed of hard materials, which can cause blood to clot. Such clots can lead to thrombosis and strokes, so anyone with an artificial heart has to take anticoagulants. In fact, Cohrs tells Mental Floss, patients with some sort of artificial heart implant—either a LVAD or a TAH—die more frequently from a stroke or an infection than they do from the heart condition that led to the implant. Neurological damage and equipment breakdown are risky side effects as well.

These complications mean that total artificial hearts are "bridges"—either to a new heart, or to death. They're designed to extend the life of a critically ill patient long enough to get on (or to the top of) the heart transplant list, or, if they're not a candidate for transplant, to make the last few years of a person's life more functional. A Turkish patient currently holds the record for the longest time living with a SynCardia artificial heart: The implant has been in his chest for five years. Most TAH patients live at least one year, but survival rates drop off after that.

The ETH team set out to make an artificial heart that would be not a bridge, but a true replacement. "When we heard about these problems, we thought about how we can make an artificial heart that doesn't have side effects," he recalls.

USING AN ANCIENT TECHNIQUE TO MAKE A MODERN MARVEL

Using common computer assisted design (CAD) software, they designed an ersatz organ composed of soft material that hews closely to the composition, form, and function of the human heart. "Our working hypothesis is that when you have such a device which mimics the human heart in function and form, you will have less side effects," Cohrs says.

To create a heart, "we take a CT scan of a patient, then put it into a computer file and design the artificial heart around it in close resemblance to the patient's heart, so it always fits inside [the body]," Cohrs says.

But though it's modeled on a patient's heart and looks eerily like one, it's not identical to the real organ. For one thing, it can't move on its own, so the team had to make some modifications. They omitted the upper chambers, called atria, which collect and store blood, but included the lower chambers, called ventricles, which pump blood. In a real heart, the left and right sides are separated by the septum. Here, the team replaced the septum with an expansion chamber that is inflated and deflated with pressurized air. This action mimics heart muscle contractions that push blood from the heart.

The next step was to 3D-print a negative mold of the heart in ABS, a thermoplastic commonly used in 3D printing. It takes about 40 hours on the older-model 3D printers they have in the lab. They then filled this mold with the "heart" material—initially silicone—and let it cure for 36 hours, first at room temperature and then in an oven kept at a low temperature (about 150°F). The next day, they bathed it in a solvent of acetone, which dissolved the mold but left the printed heart alone. This process is essentially lost-wax casting, a technique used virtually unchanged for the past 4000 years to make metal objects, especially bronze. It takes about four days.

The resulting soft heart weighs about 13 ounces—about one-third more than an average adult heart (about 10 ounces). If implanted in a body, it would be sutured to the valves, arteries, and veins that bring blood through the body. Like existing ventricular assist devices and total artificial hearts on the market, it would be powered by a portable pneumatic driver worn externally by the patient.

FROM 3000 TO 1 MILLION HEARTBEATS

In April 2016, they did a feasibility test to see if their silicone organ could pump blood like a real heart. First they incorporated state-of-the-art artificial valves used every day in heart surgeries around the world. These would direct the flow of blood. Then, collaborating with a team of mechanical engineers from ETH, they placed the heart in a hybrid mock circulation machine, which measures and simulates the human cardiovascular system. "You can really measure the relevant data without having to put your heart into an animal," says Cohrs.

Here's what the test looked like.

"Our results were very nice," Cohrs says. "When you look at the pressure waveform in the aorta, it really looked like the pressure waveform from the human heart, so that blood flow is very comparable to the blood flow from a real human heart."

Their results were published earlier this year in the journal Artificial Organs.

But less promising was the number of heartbeats the heart lasted before rupturing under stress. (On repeated tests, the heart always ruptured in the same place: a weak point between the expansion chamber and the left ventricle where the membrane was apparently too thin.) With the average human heart beating 2.5 billion times in a lifetime, 3000 heartbeats wouldn't get a patient far.

But they're making progress. Since then, they've switched the heart material from silicone to a high-tech polymer. The latest version of the heart—one of which was stuck in that box in the Tallinn airport—lasts for 1 million heartbeats. That's an exponential increase from 3000—but it's still only about 10 days' worth of life.

Right now, the heart costs around $400 USD to produce, "but when you want to do it under conditions where you can manufacture a device where it can be implanted into a body, it will be much more expensive," Cohrs says.

The researchers know they're far from having produced an implantable TAH; this soft heart represents a new concept for future artificial heart development that could one day lead to transplant centers using widely available, easy-to-use design software and commercially available 3D-printers to create a personalized heart for each patient. This kind of artificial heart would be not a bridge to transplantation or, in a few short years, death, but one that would take a person through many years of life.

"My personal goal is to have an artificial heart where you don't have side effects and you don't have any heart problems anymore, so it would last pretty much forever," Cohrs says. Well, perhaps not forever: "An artificial heart valve last 15 years at the moment. Maybe something like that."

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History
How an Early Female Travel Writer Became an Immunization Pioneer
Lady Mary Wortley Montagu by A. Devéria
Lady Mary Wortley Montagu by A. Devéria

Lady Mary Wortley Montagu was a British aristocrat, feminist, and writer who was famed for her letters. If that were all she did, she would be a slightly obscure example of a travel writer and early feminist. But she was also an important public health advocate who is largely responsible for the adoption of inoculation against smallpox—one of the earliest forms of immunization—in England.

Smallpox was a scourge right up until the mid-20th century. Caused by two strains of Variola virus, the disease had a mortality rate of up to 35 percent. If you lived, you were left with unsightly scars, and possible complications such as severe arthritis and blindness.

Lady Montagu knew smallpox well: Her brother died of it at the age of 20, and in late 1715, she contracted the disease herself. She survived, but her looks did not; she lost her eyelashes and was left with deeply pitted skin on her face.

When Lady Montagu’s husband, Edward Wortley Montagu, was appointed ambassador to Turkey the year after her illness, she accompanied him and took up residence in Constantinople (now Istanbul). The lively letters she wrote home described the world of the Middle East to her English friends and served for many as an introduction to Muslim society.

One of the many things Lady Montagu wrote home about was the practice of variolation, a type of inoculation practiced in Asia and Africa likely starting around the 15th or 16th century. In variolation, a small bit of a pustule from someone with a mild case of smallpox is placed into one or more cuts on someone who has not had the disease. A week or so later, the person comes down with a mild case of smallpox and is immune to the disease ever after.

Lady Montagu described the process in a 1717 letter:

"There is a set of old women, who make it their business to perform the operation, every autumn, in the month of September, when the great heat is abated. People send to one another to know if any of their family has a mind to have the small-pox: they make parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old woman comes with a nuts-hell full of the matter of the best sort of small-pox, and asks what veins you please to have opened. She immediately rips open that you offer to her with a large needle (which gives you no more pain than a common scratch), and puts into the vein as much matter as can lye upon the head of her needle, and after that binds up the little wound with a hollow bit of shell; and in this manner opens four or five veins. . . . The children or young patients play together all the rest of the day, and are in perfect health to the eighth. Then the fever begins to seize them, and they keep their beds two days, very seldom three. They have very rarely above twenty or thirty in their faces, which never mark; and in eight days' time they are as well as before their illness."

So impressed was Lady Montagu by the effectiveness of variolation that she had a Scottish doctor who worked at the embassy, Charles Maitland, variolate her 5-year-old son in 1718 with the help of a local woman. She returned to England later that same year. In 1721, a smallpox epidemic hit London, and Montagu had Maitland (who by then had also returned to England) variolate her 4-year-old daughter in the presence of several prominent doctors. Maitland later ran an early version of a clinical trial of the procedure on six condemned inmates in Newgate Prison, who were promised their freedom if they took part in the experiment. All six lived, and those later exposed to smallpox were immune. Maitland then repeated the experiment on a group of orphaned children with the same results.

A painting of Lady Mary Wortley Montagu with her son, Edward Wortley Montagu, and attendants
Lady Mary Wortley Montagu with her son, Edward Wortley Montagu, and attendants
Jean-Baptiste Vanmour, Art UK // CC BY-NC-ND

But the idea of purposely giving someone a disease was not an easy sell, especially since about 2 or 3 percent of people who were variolated still died of smallpox (either because the procedure didn’t work, or because they caught a different strain than the one they had been variolated with). In addition, variolated people could also spread the disease while they were infectious. Lady Montagu also faced criticism because the procedure was seen as “Oriental,” and because of her gender.

But from the start, Lady Montagu knew that getting variolation accepted would be an uphill battle. In the same letter as her first description of the practice, she wrote:

"I am patriot enough to take pains to bring this useful invention into fashion in England; and I should not fail to write to some of our doctors very particularly about it, if I knew any one of them that I thought had virtue enough to destroy such a considerable branch of their revenue for the good of mankind. But that distemper is too beneficial to them, not to expose to all their resentment the hardy wight that should undertake to put an end to it. Perhaps, if I live to return, I may, however, have courage to war with them."

As promised, Lady Montagu promoted variolation enthusiastically, encouraging the parents in her circle, visiting convalescing patients, and publishing an account of the practice in a London newspaper. Through her influence, many people, including members of the royal family, were inoculated against smallpox, starting with two daughters of the Princess of Wales in 1722. Without her advocacy, scholars say, variolation might never have caught on and smallpox would have been an even greater menace than it was. The famed poet Alexander Pope said that for her, immortality would be "a due reward" for "an action which all posterity may feel the advantage of," namely the "world’s being freed from the future terrors of the small-pox."

Variolation was performed in England for another 70 years, until Edward Jenner introduced vaccination using cowpox in 1796. Vaccination was instrumental in finally stopping smallpox: In 1980, it became the first (and so far, only) human disease to be completely eradicated worldwide.

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Medicine
New Cancer-Fighting Nanobots Can Track Down Tumors and Cut Off Their Blood Supply
iStock
iStock

Scientists have developed a new way to cut off the blood flow to cancerous tumors, causing them to eventually shrivel up and die. As Business Insider reports, the new treatment uses a design inspired by origami to infiltrate crucial blood vessels while leaving the rest of the body unharmed.

A team of molecular chemists from Arizona State University and the Chinese Academy of Sciences describe their method in the journal Nature Biotechnology. First, they constructed robots that are 1000 times smaller than a human hair from strands of DNA. These tiny devices contain enzymes called thrombin that encourage blood clotting, and they're rolled up tightly enough to keep the substance contained.

Next, researchers injected the robots into the bloodstreams of mice and small pigs sick with different types of cancer. The DNA sought the tumor in the body while leaving healthy cells alone. The robot knew when it reached the tumor and responded by unfurling and releasing the thrombin into the blood vessel that fed it. A clot started to form, eventually blocking off the tumor's blood supply and causing the cancerous tissues to die.

The treatment has been tested on dozen of animals with breast, lung, skin, and ovarian cancers. In mice, the average life expectancy doubled, and in three of the skin cancer cases tumors regressed completely.

Researchers are optimistic about the therapy's effectiveness on cancers throughout the body. There's not much variation between the blood vessels that supply tumors, whether they're in an ovary in or a prostate. So if triggering a blood clot causes one type of tumor to waste away, the same method holds promise for other cancers.

But before the scientists think too far ahead, they'll need to test the treatments on human patients. Nanobots have been an appealing cancer-fighting option to researchers for years. If effective, the machines can target cancer at the microscopic level without causing harm to healthy cells. But if something goes wrong, the bots could end up attacking the wrong tissue and leave the patient worse off. Study co-author Hao Yan believes this latest method may be the one that gets it right. He said in a statement, "I think we are much closer to real, practical medical applications of the technology."

[h/t Business Insider]

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