Research Yields New Weapons to Fight Bacterial Enemies

Research Yields New Weapons to Fight Bacterial Enemies

Recent advancements in modern dentistry have resulted in dental visits that are shorter, safer, more comfortable, and introduced restorative materials with improved function and esthetics. However, despite efforts from both research and manufacturing communities, dental restorations continue to fail due to secondary caries, which not only is inconvenient, but often expensive. Estimates suggest the annual cost of treating oral biofilm-related diseases in the United States is nearly $81 billion. Research conducted at the University of Oklahoma College of Dentistry is poised to introduce new materials – a secret weapon - to fight oral bacteria that cause dental restorations to fail.

On the forefront of developing that secret weapon, OU College of Dentistry researcher Fernando Luis Esteban Florez, D.D.S., M.S., Ph.D., assistant professor, Division of Dental Biomaterials Department of Restorative Sciences, obtained a grant from the Oklahoma Center for the Advancement of Science and Technology (OCAST). The team also includes the expertise of Sharukh Khajotia, B.D.S., M.S., Ph.D., Associate Dean for Research and Innovation, OU College of Dentistry, and researchers from the University of Oklahoma Norman campus, Yingtao Liu, M.S., Ph.D., associate professor of Aerospace and Mechanical Engineering; Pedro Huebner, MIE, Ph.D., assistant professor of Industrial and Systems Engineering; and Javier Jo, M.S., Ph.D., professor of Electrical and Computer Engineering.  

The treatment of primary dental caries is a multi-step procedure that involves the removal of affected tooth structure using rotary instruments, followed by an acid etching step and the application of dental adhesive resin to seal mineralized tissues and promote bonding between tooth structures and filling materials. However, dental adhesive resins are degraded over time by a combination of water, enzymes from saliva, oral bacteria, acidity, temperature variations and cyclical masticatory forces that allow pathogenic bacteria to penetrate through the adhesive to form caries-producing biofilms, considered the major cause of failure of dental restorations. This common problem caused the researchers to ask, “What if adhesive resins used in restorative dentistry could not only create the necessary bond between filling and tooth, but also could fight against bacteria that attack it?” 

Esteban Florez and Khajotia proposed a solution in the form of nitrogen-doped titanium dioxide nanoparticles.

So intriguing was the question, and so promising the anticipated outcomes, that the researchers submitted a grant proposal, which OCAST awarded in the amount of $135,000 for a three-year grant period. 

“A nanoparticle can be 750 times smaller than the thickness of a human hair,” Khajotia said. “The properties of many conventional materials change when formed from nanoparticles because they have a great surface-to-volume ratio compared to larger particles.”  

The research proposal awarded specifically responds to the 2020 Oklahoma Health Research Program funding opportunity. “It is a logical next step in my long-term career goal to pursue new strategies to prevent the occurrence of secondary caries,” said Esteban Florez. “This includes the development of a novel antibacterial adhesive resin with long-term, non-leaching antibacterial properties, and the optimization of an ultra-bright high throughput, non-destructive and real-time bioluminescence assay to assess the metabolic activity of intact oral biofilms.”

It is anticipated that knowledge gained from the present research proposal will give Esteban Florez the experience, knowledge, preliminary data and critical mass of publications to support a request for additional funding from the National Institutes of Health. 

Esteban Florez and Khajotia determined they needed to construct higher quality nanoparticles and make them functional within dental polymers to create the adhesive resin. To achieve this, they established a collaboration with Adam Rondinone, Ph.D., a scientist from the Center for Nanophase and Materials Sciences at Oak Ridge National Laboratory in Oak Ridge, Tennessee.

This multidisciplinary team began to fabricate nitrogen-doped titanium dioxide nanoparticles using highly controllable and robust synthesis processes based on solvothermal reactions. Unlike other adhesive resins, the materials developed display antibacterial properties, which are enhanced by on-demand visible light irradiation. 

The team investigated the nanoparticles using latest generation scientific technologies available at Oak Ridge, including time-of-flight secondary ion spectrometry, small-angle X-ray spectroscopy, small-angle neutron scattering and advanced microscopies, such as helium-ion and dual-FIB SEM (focused ion beam scanning electron microscope). 

“Using neutron scattering, we can understand how well the nanoparticles are dispersed, how they impact polymer chains, and what types of interfaces are established between the polymer and nanoparticles,” Esteban Florez said. 

The research is promising, and the team is hopeful about its translation into practice. The OCAST Health Research Program makes it possible to pursue a much broader range of possibilities. For now, it has led to other findings, such as the nanoparticles’ ability to produce crystals containing high concentrations of phosphorous and calcium from saliva-like solutions.

Today, the research team holds two international patents. Current research is ongoing into functionalizing nanoparticles in areas other than dentistry, including antibacterial coatings for the control of cross-contamination in hospital settings, development of 3-D printed air filters with long-term and self-cleaning functionalities.