In a dimly lit room the size of a boxcar, a patient at Fort Sam Houston in Texas lay on a U.S. Army gurney. A split in the skin over his knee revealed a nasty wound: broken shin, muscles bruised and burned, protective membranes shredded. On top of all that, it was infected. His doctors stared down at the wound, perplexed. Bacteria infection had returned to the wound, though most of the infection had been eliminated when the wound was cleaned two days earlier.
When Drs. Warren Haggard and Joel Bumgardner, biomedical engineering professors in the Herff College of Engineering at the University of Memphis, went looking for an answer to a problem plaguing U.S. Army doctors, one couldn’t help but think of the clever marketing jingle from the 1950s: “Plop plop, fizz fizz, oh what a relief it is.”
“What the Army was looking for,” Haggard says, “was a way to improve their treatment of infection. They were looking for a way to decrease the contamination in the wound by adding an adjunctive therapy.”
Herff College of Engineering professors Joel Bumgardner (left) and Warren Haggard (right) have developed a fast-acting dissolvable pellet that can deliver antibiotics to wounded soldiers in war zones, thus decreasing or eliminating infection.
About two years ago, the American Academy of Orthopedic Surgeons and the U.S. Army lobbied Congress to fund research designed to accelerate progress in the area of complex injury care. Haggard, attending an Academy meeting, found out about the availability of grant money and submitted a proposal for research.
What Haggard and Bumgardner would eventually provide the U.S. Army with was a delivery mechanism of antibiotics that resembled the action of an Alka Seltzer: drop a rapidly dissolving pellet loaded with antibiotics directly into a soldier’s complex, contaminated wound. The result? Better management of the wound and less loss of limb or even life.
Bumgardner and Haggard had spent months researching a rapidly resorbing controlled delivery technology for use by the Army to treat these complex contaminated extremity wounds. What they created was a local delivery technology they named “Fast Pellet.”
“It combines a known biomaterial, calcium sulfate, and an antibiotic, amikacin, for early adjunctive therapy to lessen or prevent wound infections,” says Haggard. “It is sprinkled directly into the wound - we are putting the antibiotic into the local environment.”
To see the benefit of the Fast Pellet, one must know what happens in field hospitals in war zones. Wounds to soldiers are initially cleaned with saline solution, but because of the amount of time it takes to transport a wounded soldier to a permanent hospital - 24 to 48 hours in some cases - wound complications, such as infection, may arise. Simply cleaning the wound may not in itself remove all the bacteria. Existing bacteria can colonize, or new bacteria can be introduced during transport, re-infecting the wound, similar to what happened to the patient at the U.S. Army Institute of Surgical Research at Fort Sam Houston.
“They can wash out about 90 percent of the bacteria, but the pellets will get the ones that are hiding,” Bumgardner says of the initial cleaning.
Before he came to the University, Haggard worked at Wright Medical Technology Inc., maker of Osteoset®-T. This product is much like another technology that delivers medicine via a non-degradable bone cement bead that must eventually be removed from a wound. But Wright’s Osteoset®-T, in pellet form, dissolves. A month after it’s placed in a wound, it’s gone. It is used for chronic infections.
Haggard set out to develop a pellet that would dissolve in less than 24 hours and would be used for complex contaminated wounds. He imagined a pellet that would break down quickly when placed in a wound, “like an Alka-Seltzer.”
In Haggard’s lab, graduate student Stephanie Jackson began studying the contents of a small test tube that was filled with water set at body temperature. Pellets were placed in the water and every few hours, Jackson would remove and weigh them. At the end of each 48-hour round, she checked to see how quickly the pellets had dissolved. Sometimes the pellets, roughly the size of aspirins, broke down too quickly. Other times, too slowly.
“We did dissolution testing to see if the pellets would dissolve fast enough,” Haggard says, “and elution testing to see if they would release this antibiotic over this short period of time.”
From the outside, the pellets don’t look very different from other calcium sulfate pellets, but inside, they’re fundamentally different. And that’s what makes them work.
Even though the pellets are made from calcium sulfate, most calcium sulfate pellets are created by combining the hemihydrate form of the chemical - commonly known as plaster of Paris -with water and antibiotic to create a dihydrate antibiotic-loaded pellet. The “Fast Pellet,” on the other hand, is created by mixing dihydrate calcium sulfate with an antibiotic and a sort of cellulose-based glue. This is the way most pills — vitamins, for instance - keep their shape.
Coming up with this formula was a team effort. Haggard and Bumgardner worked with research associate Kelly Richelsoph to perfect the pellet.
“It’s the same calcium and sulfate ions,” Bumgardner explains, “but they’re arranged somewhat differently.” Variations in crystal structure and, therefore, surface area, allow the pellet to break down at the correct rate.
The team finally settled on a formula that was workable. The pellets dissolved in roughly eight hours, releasing a steady stream of antibiotic along the way. Thus was born the “Fast Pellet.”
Haggard and Jackson sent some of the water samples that had been used in the elution testing to microbiologist Dr. Harry Courtney at the Veterans Affairs Hospital in Memphis. Courtney put the water together with bacteria to see if antibiotics in the water would kill the bacteria, which they did. Convinced the pellets would work, Haggard, Richelsoph and Jackson transported them to the U.S. Army Institute of Surgical Research at Fort Sam Houston.
There, they met with Army researchers and surgeons and watched them repeat the study they had done more than two years before. But this time, after cleaning the wound, the surgeon placed 50 Fast Pellets inside an animal test subject. Then, using staples and wound dressing, the surgeon closed the wound. If everything worked as planned, the wound would still be clean two days later.
Forty-two hours after cleaning the wound and placing the pellets in it, the test-subject was examined again. Unlike two years earlier when researchers and surgeons discovered bacteria had dramatically increased, this time a very, very small number of bacteria were present. The pellets had dissolved but not before doing what they were meant to do: kill the bacteria and destroy the infection.
Simply cleaning the wound reduced the bacteria count by one order of magnitude. The pellets reduced the count by three orders of magnitude. “That’s not a hundred times less,” Haggard says, “that’s a thousand times less bacteria.”
The technology may eventually have far-reaching applications.
“While this technology is intended for the cure of injuries sustained on the battlefield, this adjunctive therapy may be applicable to traumatic extremity wounds sustained by the civilian population, resulting from motorized vehicle accidents, gunshot wounds, sports injuries and natural disasters, like Hurricane Katrina,” says Haggard.
The University’s director of Technology Transfer and Research Development, Kevin Boggs, has filed a patent for the Fast Pellet.
Haggard and Bumgardner, meanwhile, have already started work on their next project, an improvement to the Fast Pellet. Again, they’re working for the Army, this time on a two-year grant. They’re investigating a different material, one that may even aid in the healing process.
Visit www.memphis.edu/researchvideo.htm to watch a video about the exciting research taking place at the University of Memphis.
Kevin Boggs has been here before. Not, of course, as the director of Technology Transfer and Research Development at the U of M. The University created that position last fall, and Boggs filled it in January. No, Boggs was here as a student.
Boggs had already earned a PhD in molecular and cellular biology from the Medical University of South Carolina in Charleston when a teacher suggested he consider a career in technology transfer. In 2000 he graduated with an MBA from the University of Memphis.
Technology transfer sits at the nexus of the commercial and academic worlds. Boggs has two essential duties: To help academics commercialize their inventions, and to help businesspeople access the intellectual resources at the University. Fulfilling both requires lots of tasks.
For one thing, Boggs is the point man for all new inventions. He encourages researchers to contact him directly to discuss their ideas. In fact, that's his favorite part of the job.
“The best thing,” Boggs says, “is that I'm one of the first people that a faculty member will tell about their ideas, outside of their research group, and their families. When an idea is starting to work out, whom do they call? Me.”
Then, Boggs works with attorneys to file patents for the inventions. And after that,
he seeks out companies to commercialize them. Eventually, he hopes companies - especially local ones - will come to him.
Boggs is currently working with researchers in fields like chemistry, biology and biomedical engineering, among others. He is working with biomedical engineering professors Warren Haggard and Joel Bumgardner to patent their "Fast Pellet" technology.
Even though Boggs is new to technology transfer at the University, he's been in the field for several years. He acquired most of his expertise as assistant director of technology transfer at the University of Florida, home to the researchers who, in 1965, came up with a formula (Gatorade) to keep football players hydrated.
In technology transfer, that's as good of a place to start as any. – by Pat Walters