Doctors insert more than 2 million tiny wire mesh tubes, or heart stents, into Americans’ blood vessels a year to treat heart disease, according to health care market research firm iData Research.
Stents are one of many implants used by doctors to support the body while it heals from disease or injury and, for decades, they have been made from metals that stay in the body for a long time after their job is done. Now, a new generation of biodegradable implants made from magnesium are gaining ground, but researchers in the Department of Materials Science and Engineering are investigating how the materials’ structure affects patient outcome.
The Johns Hopkins University researchers led by Professor Tim Weihs and his student Sreenivas Raguraman recently published a study in Acta Biomaterialia that demonstrated that, when processed two different ways, the same magnesium-based implant material can have dramatically different outcomes in the body. The research was conducted in collaboration with Professor Roger J. Guillory II and PhD student Mitchell L. Connon at the Medical College of Wisconsin.
“This is really important for elderly patients, who may not tolerate multiple procedures well, for soldiers with traumatic injuries, or for athletes who want to recover quickly without permanent hardware,” says Sreenivas Raguraman, the lead author on the paper and a materials science doctoral student at Johns Hopkins.
Raguraman says that these new magnesium-based implants are strong enough to support the body and safe enough to dissolve over time to avoid long-term complications or more surgeries. The FDA recently designated one of these magnesium-based stents as a “breakthrough device.”
“I think many people assume that if an implant is called ‘biodegradable,’ it simply dissolves and disappears in a straightforward, harmless way. In reality, that process is much more complex. How the material breaks down, what it releases, and how the body responds to those degradation products all matter,” says Raguraman.
But Raguraman says to make the new implants strong enough to last, scientists often add small amounts of other elements, like aluminum. That’s where the concern comes in. Aluminum has been linked to neurological issues and cellular toxicity in large amounts.
“So, the question we asked was, ‘Does that concern actually apply here? When aluminum is present in much smaller amounts?’” Raguraman says.
Raguraman and the Hopkins researchers took that question a step further and looked at how that material broke down in the body — how the aluminum was released, if it stayed close to the implant, and whether it entered the bloodstream.
Raguraman says the finding shocked him.
“Even when the material had the exact same composition and the same amount of aluminum, changing how we processed it altered its internal atomic structure. And that internal structure determined how the aluminum was released,” Raguraman says. “We saw very different outcomes in the mice, yet the only difference was how we made the material.”
Changing the way they processed the metal alloy turned out to matter a lot. It changed its internal structure. One version of the material released aluminum in a form that entered the bloodstream and could be excreted from the body. Another kept most of it localized near the implant site. It is not yet clear which one of these processes is better for long-term health outcomes and inflammation, and the research is ongoing.
“This work provides novel insight into the complex interactions between implant microstructure and the surround biological response,” says Professor Tim Weihs. “We need to think beyond the mechanical and degradation properties of the implant and focus on the local cellular response as well.”
“That insight gives us a much more powerful way to design safer medical implants” says Raguraman. As a metallurgist, this changes his approach to the problem. “We’re not just designing materials for structural performance; we’re designing them for how they interact with the biology of the body. And that opens up a completely new way of thinking about materials science.”
Raguraman’s collaborators Roger Guillory and Mitchell Connon at the Medical College of Wisconsin are now doing studies to try to understand how the body responds to these materials at the inflammation level.
“Understanding these interactions, from microstructural manipulation and how it leads to complete physiological processing, will launch us towards developing the next generation of regenerative metallic biomaterials,” says Guillory.
“At the same time, this offers an exciting opportunity from a materials design perspective,” says Raguraman, adding that the goal would be to create implantable materials that not only provide the right strength and degradation but also lead to a better biological response. “Our aim is to bring these ideas together to maximize safer, lasting implants for people.”