Although the physician who first wanted to open blocked blood vessels was described as “something of a radical” by his colleagues, even he might have been surprised by the idea of a tiny plastic scaffold that holds open an artery and then dissolves. When Charles Dotter of Oregon Health & Science University proposed in 1969 his “coil-spring endarterial tube” to accompany what is now known as angioplasty, he envisioned a tube or coil made of metal, known as a stent, that lasts forever.
For decades metal has been the norm in stents. But in October dissolvable versions reached an important milestone, with the release of clinical trial data in The New England Journal of Medicine showing a degradable device made by Abbott Vascular performed as well as its traditional counterpart. In theory, dissolvable implants reduce the risk of inflammation, blood clots and other side effects. The report not only represents the likely future of stents but also a highly visible advance from the emerging field of biodegradable technologies. Researchers in the field envision the day when most medical hardware implanted into the body—such as that used for joint repair or surgical wound support—will last only as long as it is needed.
The concept is not new—doctors have imagined it since the introduction of synthetic dissolvable stitches in the 1970s. In fact, the Abbott stent detailed in the NEJM study is made of the same polymer as the sutures. Until recently progress has been plodding, partly because the materials in degradable devices have to satisfy a long list of criteria, including strength, durability, safety and even the ability to show up on an x-ray.
Today, scientists have been increasingly able to manipulate degradable substances—many of them, like the stuff of sutures, around for decades—to perform specific functions, such as delivering drugs, aiding organ function and performing other tasks. Like a sugar cube, these materials gradually disintegrate in liquid, usually into components that the body can break down and excrete. The Abbott stent, for example, is a polymer of lactic acid, which metabolizes and ultimately exits the body as carbon dioxide and water.
The problem with most current medical implants is that “there is no material that can be placed in the body without an immunological response over time, with very few exceptions,” says Joachim Kohn of Rutgers University, with complications like inflammation and pain. Given enough time all joint replacements eventually fail, according to doctors writing in the May 2014 issue of Mediators of Inflammation. Or consider the track record of a surgical mesh used after incontinence surgery in women, in which the U.S. Food and Drug Administration recently warned that complications and failures are “not rare.”
With approximately half a million people receiving implants each year in the U.S., stents have long been attractive for developers of degradable technology. The device’s purpose is to support a vessel as it recovers from angioplasty, which uses a small balloon at the end of a catheter to widen a narrowed artery. Modern stents are coated with drugs that help prevent scar tissue from forming and plaque from reestablishing itself. Within a year the vessel is fully restored but the implants are not removed. That means the artery can never return to its original flexibility. Long-term risks, like the return of blockage, are small but real.
More than a dozen companies have degradable stents in development. Manufacturers tend to stick to materials that are already used in medicine or known to be metabolized by the body. Approval of an entirely new polymer would add to the time and expense of development. Whereas some companies are developing stents made of iron and manganese—common nutrients that the body can easily break down—Abbot’s stent is made of poly(L-lactic acid), or PLLA, a lactic acid chain that commonly used in medicine.
Once the entire drug is delivered, and the vessel has healed, the degradable stent gradually vanishes over the first few years. “They are so different from metal stents we don’t even call them stents any more. We call them bio-absorbable scaffolds,” says Gregg Stone of Columbia University Medical Center, one of the lead scientists in the study, which was sponsored by Abbott.
In the short term, absorbable versions need to function similarly to a traditional stent. In an Abbott-sponsored test begun in 2008 involving more than 2,000 people, the degradable stent performed as well as its metallic counterpart during the first year, although a longer comparison has not been conducted.
In practice, it sounds like a win, but some in the field remain cautious. In an editorial published with the NEJM study, Robert Byrne, a physician at the German Heart Center in Munich, was particularly uncomfortable with a short-term higher rate of clot formation among those with the dissolvable stent. The study’s authors say the difference (1.5 versus 0.7 percent) was not statistically significant but Bryne wrote that a doubling of risk would give many doctors pause. “Although the concept of self-degrading stents is intuitively attractive, promise alone is not enough to make us unconditionally embrace this technology,” he wrote in the journal.
A host of other researchers are using biodegradable substances for other types of innovative drug delivery—as a means to get drugs to exactly where they are needed, just at the time they are needed. Kohn’s lab at Rutgers has developed a drug-coated mesh that is used after hernia operations. Traditionally, surgeons insert a lattice to support the abdomen during healing. A product made by drug manufacturer TyRx Pharma (a company Kohn founded that was acquired by Medtronic in 2014) was approved by the FDA in 2006 and contains an antibiotic that seeps into the incision as it heals. A similar product that encases pacemakers and other small cardiac devices has dramatically reduced infection rates in clinical trials.
Kohn envisions other uses for degradable meshes. He points out the number of knee replacement operations have soared, often because the cartilage has become worn or damaged beyond repair. Doctors are experimenting with ways to grow new cartilage cells in the laboratory and insert them into the joint. In the September Tissue Engineering, Part C: Methods, Kohn’s team described a degradable scaffold that could be used to buttress these new cells as they grow and strengthen. “If we could simply help the body heal itself and create a cell based–therapy and a temporary scaffold that induces them to integrate into the disease cartilage and repair it, we could essentially eliminate the vast majority of all knee replacements,” Kohn says.
Not all potential applications are passive. Christopher Bettinger, a materials scientist at Carnegie Mellon University, is working to encapsulate oral medication in battery-powered devices that can be programmed to deliver drugs exactly when and where they are needed. As he described in 2013 in Proceedings of the National Academy of Sciences, the negative terminal of the battery is melanin pigment, the positive is manganese dioxide, and the fluid electrolyte between the two “is basically like Gatorade.” The advantage of battery-powered drug delivery is timing: the device could be programmed to deliver a set amount of drug to a specific site along the digestive tract.
The day is also coming when the versatility and function of common electronics at your fingertips might be available in degradable, implantable technologies, says John Rogers, a chemist at the University of Illinois at Urbana–Champaign. In 2012 Rogers and his team reported in Science the first biodegradable silicon circuit, which also contains magnesium, magnesium oxide and silk. Among other projects, his team is now experimenting with instruments that would allow doctors to wirelessly stimulate damaged nerves to promote healing. “The eureka moment for me was the realization that silicon, in the same, high-performance form that is used in electronic devices, is bio-resorbable,” Rogers says. In the body, if the silicon is thin enough, it degrades in the presence of water into silicic acid, which is not harmful to health, and even sold as a dietary supplement. One means of controlling the speed of disintegration is to adjust the thickness, or coat it with another biodegradable material. “There’s an accelerating trend over just the last three years in which researchers are beginning to exploit electronic devices in biodegradable forms, with all of the sophistication that is available in modern semiconductor technology,” he notes.
So one day doctors may be able to implant what are essentially dissolvable minicomputers—an idea that might have even been outside Charles Dotter’s radical imagination.