Image by courtesy
Associate Professor of Biomedical Engineering Chiara Ghezzi, right, in her lab with biomedical engineering Ph.D. student Anyelo Diaz.
They look like human teeth and gums, perhaps a partial denture that someone is about to put into their mouth to start the day. However, their location, in a lab on North Campus, offers a hint that they are not dentures at all, but rather leading-edge 3D tissue models that are at the heart of groundbreaking research being conducted by Biomedical Engineering Associate Professor Chiara Ghezzi.
Ghezzi was recently awarded two prestigious National Institutes of Health (NIH) grants totaling more than $2.6 million to support her research. The first is the Maximizing Investigators鈥� Research Award (MIRA), which she followed with a High Priority, Short Term Research Award a few weeks later. Each of the projects focuses on the mouth鈥檚 microbiome, or specific population of bacteria, fungi and viruses 鈥� mostly bacteria. Both use tissue models of the human mouth that Ghezzi developed.听听
"Dr. Ghezzi is a pioneer in tissue-engineering research,鈥� says Susan Roberts, dean of the Francis College of Engineering. 鈥淗er creativity in developing new strategies to study the oral microbiome and inflammation will have huge impacts on health and the treatment of disease.鈥澨�
Last year,听Ghezzi was awarded a five-year, $650,000 CAREER听grant from the National Science Foundation for research on the connection between human oral tissue and the oral microbiome and how they interact.
鈥楾he Mouth Is a Reservoir of Bacteria鈥�
Using the MIRA grant of $2.1 million over five years, Ghezzi will research the relationship between a woman鈥檚 fluctuating hormone levels, the mouth microbiome, and diseases and conditions known to have a sex bias.听听
鈥淭he mouth is a reservoir for bacteria,鈥� Ghezzi says. 鈥淪ome are good bacteria, and others are bad bacteria鈥� that cause various diseases. The bacteria that start off in our mouths don鈥檛 stay there: 鈥淭hey are found in our gut, brain, vagina, even in our babies鈥� placentas when we are pregnant.鈥�
Image by courtesy
The 3D tissue model that Ghezzi developed looks and acts like part of the human mouth.
The relationship between the mouth鈥檚 microbiome and diseases and conditions known to be more common or more serious in people of a particular sex is relatively unexplored. Yet, Ghezzi says, existing research suggests that there are links. For example, she says, 鈥淭here is a strong correlation between poor oral conditions and negative pregnancy outcomes.鈥�
The research also has the potential to illuminate the role of hormones and the microbiome in diseases that show a strong sex bias, such as Alzheimer鈥檚 disease (almost two-thirds of Americans living with Alzheimer鈥檚 are women, according to the Alzheimer鈥檚 Association) and lupus (some 90% of the 1.5 million Americans living with the disease are women, according to the Lupus Foundation of America).
MIRA was created to allow innovative early-stage researchers to spend more time in the lab and less time applying for grants, which is why it鈥檚 awarded over five years instead of the shorter terms of other NIH grants. It also allows researchers to adjust their focus as their research progresses, to follow unforeseen results where they lead.听听
The grant allows Ghezzi to explore women鈥檚 health, a topic she believes does not get enough research. The structure of the grant, she says, 鈥渋s an expression of the trust they give to the researcher. It funds freedom.鈥澨�
Second NIH Grant Will Help Advance 3D Tissue Model
Ghezzi鈥檚 second NIH grant of $540,000 over two years will, among other important goals, allow the 3D tissue model that she previously developed to grow in sophistication to match her research objectives. This research will trace how healthy mouth microbiomes shift to welcome bad bacteria that cause disease.听听
To do this, Ghezzi and her research team will use a 3D human tissue model similar to the one they will use on the MIRA research on varying hormone levels. This model uses natural sources of protein and collagen to create sponge-like scaffolding. The scaffold is then bathed in human tissue cells, which lodge in the openings, creating a model that both looks and acts like three human molars in gums, or gingiva. It even has those gaps between tooth and gums, called periodontal pockets, where bacteria like to collect.
Image by courtesy
Ghezzi, left, works with biomedical engineering Ph.D. student Grace Callen to prepare silk fibroin, a silk protein that is an ingredient in the scaffolding for the 3D tissue model.
The model mouth is bathed in synthetic saliva. It鈥檚 so much like a human mouth that bacteria even take their usual layered positions there, with oxygen-loving bacteria on the surface and the bacteria that don鈥檛 need or even avoid oxygen hiding in the crevices 鈥� in some cases, underneath other bacteria.
What will make the new tissue model different, and allow Ghezzi to research the moment of shift between healthy and unhealthy tissues for diseases like gingivitis, is that it will include immune cells as well.听
鈥淭he Holy Grail of tissue modeling is immune system modeling,鈥� Ghezzi says.
The award also will allow Ghezzi to bring on additional researchers at the graduate and postdoctoral levels. Those increased opportunities will benefit the university community, just as the research itself offers the broader benefit of insights into helping people stay healthier.听听
Says Roberts, 鈥淗er efforts contribute significantly to the profile of research at 51视频 in bioengineering and biomanufacturing and reflect our innovative approaches to solving problems at the interface of engineering and the life sciences."