Master’s degree candidate Sagar Kaushik of the University of Alabama at Birmingham (UAB) won a 2015 Graduate Design and Research Award from the Biomedical Engineering Society for his nanogel, which could replace root canal treatments with a single injection. Yet his work is not over.
Kaushik’s interest in oral health started in high school when he began investigating alternatives to antibiotics for periodontal disease as he competed in science fairs. Later, he met Dr. Ho-Wuk Jun in the Science and Technology Honors Program at UAB.
“My freshman year, I joined Dr. Jun’s lab. He basically trained me on what we were doing in the lab that first year,” Kaushik said. “And then I started my sophomore year, when he offered me this project.”
Jun already had completed research in using nanogels to repair broken cartilage and bone and regenerate damaged heart tissue, and Kaushik had worked on those projects. A specially formulated and injected nanogel in these areas provides an extracellular matrix or framework for new blood vessels to grow, accelerating healing.
Dr. Kyounga Cheon, however, suggested using the nanogel to treat infections and rejuvenate teeth that otherwise would be lost to root canals, since teeth die when they lack healthy blood vessels. But before new blood vessels could grow into the gel’s biomimetic nanomatrix, a pair of antibiotics in it would combat bacteria.
“We chose ciprofloxacin and metronidazole,” Kaushik said, noting that they are 2 of the 3 most commonly used antibiotics in root canal treatment. “We removed the minocycline because of its side effects of tooth discoloration and weakened dental formation.”
The ciprofloxacin in particular is effective in fighting recurring bacterial infections. Also, the local application of the antibiotics via injection instead of oral administration means a lower dose can achieve a more potent effect. The reduced quantity also helps to minimize the potential for developing bacterial resistance.
Then, lycene groups in the gel enable a sustained and steady release of its nitric oxide component, which new blood vessels use as fuel for their growth. These blood vessels would grow from healthy tissue through the nanomatrix and into the damaged tissue, feeding on the nitric oxide and getting support from the gel.
“If you look at the roots of a plant, if one standard root dies, what happens is since it shriveled and doesn’t have any water, basically there’s no way you can bring that root back to life,” Kaushik said. “But you could still bring the rest of the plant back to life if you have new roots shoot into the same area.”
Kaushik and a pair of undergraduates began with specific, known strains of bacteria. Now, they are using clinical samples taken from patients with severely damaged dentin and pulp at the endodontic clinic at UAB, meaning the researchers must identify and quantify the bacteria. Next, they will begin experiments with canines.
“We would be doing this in a beagle model,” said Kaushik. “We would basically first infect the beagle with the same, known bacterial strains and then let them grow. And then we would inject our gel into that infected area and watch the growth of the tooth. We’re looking for 2 things. The first one is if the infection goes away. The second would be if the tooth itself is regenerated. That’s our main goal.”
With the animal model process underway, Kaushik expects this stage of the research to take place over the next couple of months and be nearly complete by the middle of February. If the beagle model experiments go well, Kaushik believes human testing will follow.
“At that point it just depends on how, basically, we would set up the human studies and do the clinical trials for that, whether at UAB or whether it would be taken somewhere else,” he said.
Time is running out for Kaushik, too. He will complete his master’s degree by summer 2016. After that, he hopes to go to medical school, with an application at UAB already submitted. No matter where he goes next fall, though, he admits he won’t be available to commit the time required to see the research through its later stages.
“I think for the most part it would be passed off. I’d still be involved as much as I can. I’d love to be involved as much as I can,” he said. “But I don’t know how much time I’ll have during the semester. It would mostly be in the summer. We have the summer off, and I would be able to help.”
Regardless of his involvement later, though, Kaushik values the time he has already dedicated to developing the nanogel.
“This was definitely a great opportunity from UAB by Dr. Jun and Dr. Cheon,” Kaushik said, “who basically gave an undergraduate and trusted an undergraduate with such a responsibility to actually let me research independently as much as possible.”
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