Engineering better medicine - one bead at a time

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Medical doctors at McLaren Regional Medical Center and mechanical engineers at Kettering University have teamed-up to improve medical care for patients with massive soft tissue injuries to skin and muscle tissue, and persistent joint infections. Their research centered around beads of bone cement, polymethylmethacrylate, a substance commonly used in orthopaedic surgeries.

So what does bone cement have to do with skin and muscle injuries? Previous research had found "when patients suffered massive soft tissue defects or damage that involved a lot of dirt and grime introduced into their biological system, there was a huge risk of infection," said Dr. Patrick Atkinson, associate professor of Mechanical Engineering at Kettering. "Even if the patient was put on a triple antibiotic IV, there was still the potential for localized infections to the area," he said.

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Doctors determined that a localized, but slowly delivered administration of antibiotic to the area was the best course of action. Because bone cement was a substance already accepted by the human body, antibiotics were mixed into bone cement beads, which were packed into damaged muscle through the wound. "Instead of a systemic loading of antibiotic," said Atkinson, "the bone cement leaches out only in the area susceptible to infection. Elution (leaching of antibiotic solution) occurs at the proper rate to keep the risk of infection down."

Bone cement beads have typically been molded onto a length of suture called a string of beads. About the size of a gumball, there are approximately 10 beads on a string. The reason they are put on a string, said Atkinson, is that they will more easily pack into the muscle. After inserting the string of beads, the wound is closed. After two or three weeks the string can just be pulled and they will all come out. The strings are not left in the body too long, to prevent the body from healing too much and adhering to the beads.

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The research project between Kettering and McLaren was an attempt to determine the best shape and size for the beads for optimal elution. "From a medical standpoint," said Dr. Sidney N. Martin, orthopaedic surgeon and residency coordinator for the Department of Orthopaedic Surgery at McLaren, "we look at new technologies in terms of how they can help people." The use of bone cement beads isn't new technology, but improving their application is, in essence, "building a better mousetrap," Martin said.

"The transfer of this kind of science happens every day in a hospital," said Martin, "in wounds incurred from motorcycle and motor vehicle accidents, gunshots and open fractures (compound fractures), where infection can be devastating."

Using bone cement beads to deliver antibiotic "allows us to be more scientific in treating the wound - we can deliver high concentrations of antibiotic right where it's needed," Martin said. Otherwise, the antibiotic has to be delivered through the blood stream, limiting the amount of antibiotic used.

The research team included from Kettering: Atksinon, Dr. Stacy Seeley, associate professor of Chemistry; Massoud Tavakoli, professor of Mechanical Engineering; and Stephanie L. Colton, Kettering graduate student in Chemistry. McLaren Regional Medical Center researchers included: Martin; Dr. Paul Telehowski, orthopaedic surgeon; and Dr. Bryan Larson, orthopaedic surgeon. Other researchers involved in the project were Dr. John Seeley, assistant professor of Chemistry at Oakland University and Pat Forrester, PD.

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"We asked ourselves should it be a sphere or a football, should it be a big sphere or a small sphere, should it be a big football or a small football?" Atkinson said. To help answer their questions, researchers assigned a Kettering graduate student to design molds on a computer using a Rapidprototyper. The molds allowed them to create multiple beads the same size for experimentation.

"We produced a number of beads for each size," said Atkinson, and impregnated the cement with tobramyacin, a common antibiotic that is typically used to treat bacteria in muscles that have been traumatized." The elution of each bead size and shape was tested by suspending the beads by their suture in physiologic saline (water with the same salt content as the human body). Every few hours the bead was removed and the saline fluid sampled to analyze the level a tobramyacin leaching out of the bead.

Two different volumes, 1.7 cubic centimeters of materials and 5.31 cubic centimeters of materials, were used to determine whether the volume of each bead made a difference.

The researcher's original hypothesis was probably not,' because if they assumed that elution is a function of surface area, the antibiotic would have to leach from the surface area, not from the center of the bead, Atkinson said. "Even if the volume of the bead was tripled, it didn't triple the elution," said Atkinson, "so volume was a loser - it had to be surface area. And, as surface area increased, the amount of elution increased."

And, while a larger bead has more surface area than a smaller bead, more smaller beads would have more total surface area than fewer large beads, based on the same amount of bone cement per packet. It turns out that a football shape has more surface area than a sphere.

"So, more little beads are better than bigger beads, and football shapes are better than spheres," he said.

"Unlike our research using molded beads, in the operating room beads are hand molded for insertion into the body to custom make them for better control of what is needed," said Atkinson. Martin added that he would like to have a method to standardize the production of bone cement beads. "Standardizing the beads would enable them to be even smaller," he said.

It is expected that after the team of researchers publishes its results, the medical community will alter the shape of beads used for eluting antibiotics into soft tissue wounds. "We basically took a common medical practice and tweaked it to optimize it," said Atkinson.

Written by Dawn Hibbard
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