Man-made medical mystery gets second solution

5 min read

MGH researchers develop new material to ward off implant bone loss

Researchers have created a new material that they believe improves on an eight-year-old solution to a decades-long medical mystery over the cause of widespread artificial joint failure.

The new material, developed at Harvard-affiliated Massachusetts General Hospital (MGH) and implanted for the first time July 19, could help fill the demand for higher-performance joints from a new generation of patients.

“If you’re a marathon runner, an iron man, or an [active] baby boomer, those people need really, really strong implants. These patients used to be the outliers, now they’re moving towards the center of the distribution,” said Orhun Muratoglu, associate professor of orthopedic surgery at Harvard Medical School (HMS) and head of MGH’s Orthopaedics Biomechanics and Biomaterials Laboratory. “Expectations are totally different now.”

For years, total joint replacement – a procedure pioneered in the 1950s – had been done predominantly with artificial joints made of metal and ultra-high molecular weight polyethylene. The polyethylene, a smooth, hard plastic used in a wide variety of applications, including kitchen cutting boards and the bottoms of skis, mimics the lubricating qualities of naturally occurring cartilage.

Deterioration of the slippery cartilage – usually due to arthritis – leads to joint pain as bone grinds on bone, making movement painful and leading to joint replacement surgery.

The smooth, hard polyethylene surface seemed the perfect replacement and millions of artificial hip sockets and knee joints today are lined with the material. But roughly 10 years after the implant, problems began to appear.

Implants that had been secure were loosening and the bones surrounding the artificial joint were breaking.

William Harris, Alan Gerry Clinical Professor of Orthopedic Surgery at HMS and MGH and director emeritus of MGH’s Orthopedic Biomechanics Lab, recalls seeing a patient with a failing implant in the 1970s. The bone surrounding the implant had completely worn away and the area was loaded with immune system cells called macrophages, which ingest and destroy foreign invaders in the body. Harris said it looked like cancer.

In 1976, Harris published an article detailing four similar cases, making apparent to the medical community that there was a problem.

In the years that followed, researchers came to understand that over time the movement of the joint was wearing off tiny bits of polyethylene that were sparking an immune reaction. This reaction caused the activation of osteoclasts, a type of cell that can destroy bone.

Looking closer at the material, they found that the polyethylene’s long molecules lined up in the direction of the predominant movement. Once that happened, microscopic bits of the material would break off when the joint was moved in other directions. In a hip, for example, polyethylene molecules would align with the front-to-back movement in walking. Lifting the leg sideways, rotating it, or even crossing the legs could result in microscopic damage to the implant.

In 1990, armed with that knowledge, Harris and co-workers designed a new artificial hip simulator to test materials in different ways. They also enlisted the help of materials scientists at the Massachusetts Institute of Technology (MIT) and set to work.

MIT Professor Edward Merrill hit on the solution, Harris said. Cross-linking the long polyethylene chains by irradiating the material joined the long molecules to each other, providing strength in all directions.

But the radiation created highly reactive molecules called free radicals within the material that if not dealt with would eventually weaken the implant, causing it to break prematurely. They solved that problem by melting the material. Then Muratoglu joined the lab and introduced the idea of controlled heating during irradiation, which facilitated large-scale production of implants.

That solution, achieved in 1996 and implanted in 1998, has worked well. The new material has been used in hundreds of thousands of artificial joints around the world since 1998. But the melting slightly compromised the polyethylene’s physical properties, causing concern that, in some types of artificial joints, it might break. Consequently, it has been limited in the number and types of joints it can be used in.

Muratoglu, a materials scientist from MIT who succeeded Harris as co-director of MGH’s Orthopedic Biomechanics Lab, has hit on a new solution that he believes will allow the cross-linked polyethylene to be used in more types of artificial joints.

Since it was the final melting that compromised the material, Muratoglu has been looking for alternative ways to neutralize the free radicals. He has settled on vitamin E.

Vitamin E has well-known antioxidant properties, binding free radicals and making them harmless. Muratoglu and colleagues have pioneered a process by which the polyethylene is saturated in vitamin E before use. Joints made using the material should have the same strength as the original polyethylene while having the additional wear resistance from the cross-linked material developed in 1996.

The material should be able to be used in more types of artificial joints and in a wider array of patients. Because in the past artificial joints wore out over time, younger patients were often not considered good candidates for joint replacement. With joints designed to last longer, even those patients could benefit from the new mobility the joints provide.

“I’m really excited,” Harris said. “If [the implants] continue to behave over several decades as well as they have so far over the past nine years, we’ve really done something to benefit millions and millions of people. That’s why we’re here.”