After decades of research, Ostrow faculty member Janet Moradian-Oldak prepares to bring a short peptide that can generate a biomimetic version of tooth enamel to market.

FOR DECADES, PROFESSOR JANET MORADIAN-OLDAK has toiled in the Oldak Lab, working to better understand biomineralization — the process by which biological organisms create mineralized tissue such as shells, bones and teeth — in an effort to one day recreate the process in the laboratory.

As a scientist arriving at USC in 1992, she was looking to better understand mineralized tissues that form in nature — creatures like mussels and crabs whose soft bodies can create hard materials from the environment that surrounds them. She focused on studying the proteins in teeth.

Over time, Moradian-Oldak isolated various proteins and studied their functions. Eventually, she homed in on one particular protein — amelogenin — that creates a scaffold for crystals to organize into tooth enamel. The problem was that the amino acid building blocks were long — about 180 amino acids made up the protein. So, Moradian-Oldak, along with her graduate student Kaushik Mukherjee, had an idea: make a mini protein, a peptide, that promoted enamel growth.

It paid off. The work led her to create and test a biomimetic gel based on the mini-protein, which has now been licensed by Verdant Nature Incorporated. The company will bring Moradian-Oldak’s three-decade-long journey of research into the marketplace — eventually offering patients a new treatment.

“It’s a huge milestone,” Moradian-Oldak says. “I always wanted my research to lead to practical solutions for improving oral health.”

“Paintable” Protection

Enamel is the hardest tissue in the body — it’s closer to a bioceramic than bone or other tissues, Moradian-Oldak says. Mature enamel is a dead tissue. And once lost, it does not naturally regrow, which makes prevention and repair critical. According to the World Health Organization, about 3.7 billion people suffer from oral diseases, with enamel degradation serving as a major factor.

Moradian-Oldak studied amelogenin because it was one of the proteins that the body uses when creating tooth enamel. The protein guides calcium and phosphate into organized crystalline layers, orienting them to form a structured mineralized matrix. The peptide she created self-assembled in a similar way, creating apatite crystal layers on the tooth surface, and aligned the growth of crystals to mimic natural enamel. It repairs and remineralizes lesions and tooth surface damage. While it does not yet fully regenerate entire enamel or whole teeth, Moradian-Oldak’s studies showed that it can repair white spot lesions — chalky marks on the teeth from damage to enamel — and other defects.

It’s a big leap in the world of dental technology. Fluoride can help, providing a patch of calcium-phosphate on top of the tooth, blocking the dentinal tubules, but it doesn’t rebuild the structures beneath.

“My intention was to develop something practical, something different, something which is better than fluoride,” Moradian-Oldak says. Having an industry partner to take the innovation into marketing and licensing represents the next step.

The process wasn’t always easy. Translating a finding in a lab setting to human clinical trials can be challenging, as was the years of discussions with the Food and Drug Administration about whether the gel was a device or a drug. But it was worth it, Moradian-Oldak says. And her persistence paid off. Her advice to her mentees is the same: “Be persistent. Don’t give up. And if you have an idea and want something, you can take the time to accept the challenges in your own way, pause, but go back to it again.”

Pushing Forward to the Dental Office

It’s an exciting time to watch dental innovations like Moradian-Oldak’s gel grow, says Rosemary Kiser, director of technology licensing at USC Stevens Center for Innovation who worked on the agreement. “There’s so much going on at USC and the dental school specifically,” she says. “Dental technologies are really unique in being able to commercialize relatively quickly — and a lot of great innovation is happening all at once. There’s a lot of potential.”

Verdant Nature Inc, the company who licensed the technology, agrees.

“Amelogenin-derived oligopeptides represent one of the most promising frontiers in biomimetic dental science, and we’re excited to advance the pioneering research led by Dr. Janet Moradian-Oldak’s lab,” says Lou Graham, DDS, a founder of OraScience, an affiliate of Verdant Sciences. “We look forward to a continued collaboration with USC to deepen the understanding of how these peptides contribute to natural remineralization and oral health.”

Moradian-Oldak isn’t done with discovering how to regenerate tooth enamel. There are still a lot of unanswered questions in the field, she says. “We really don’t yet have a practical strategy for regenerating human enamel.”

She will continue to focus on the basic molecular mechanisms — how certain molecules during development fulfill their function, how they signal, how they are secreted and how they support growth of mineralized tissue — while mentoring the next generation of scientists.

The promise of her work is a new, biomimetic tool that could soon give dentists a way to repair early enamel damage more effectively than current options. “All these years I conducted basic science research,” she says. “It was really my dream to see that this research comes up to be translated and actually help.”