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’ 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’s microbiome, or specific population of bacteria, fungi and viruses – mostly bacteria. Both use tissue models of the human mouth that Ghezzi developed.
"Dr. Ghezzi is a pioneer in tissue-engineering research,” says Susan Roberts, dean of the Francis College of Engineering. “Her creativity in developing new strategies to study the oral microbiome and inflammation will have huge impacts on health and the treatment of disease.”
Last year, Ghezzi was awarded a five-year, $650,000 CAREER grant from the National Science Foundation for research on the connection between human oral tissue and the oral microbiome and how they interact.
‘The Mouth Is a Reservoir of Bacteria’
Using the MIRA grant of $2.1 million over five years, Ghezzi will research the relationship between a woman’s fluctuating hormone levels, the mouth microbiome, and diseases and conditions known to have a sex bias.
“The mouth is a reservoir for bacteria,” Ghezzi says. “Some are good bacteria, and others are bad bacteria” that cause various diseases. The bacteria that start off in our mouths don’t stay there: “They are found in our gut, brain, vagina, even in our babies’ placentas when we are pregnant.”
Image by courtesy
The 3D tissue model that Ghezzi developed looks and acts like part of the human mouth.
The relationship between the mouth’s 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, “There is a strong correlation between poor oral conditions and negative pregnancy outcomes.”
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’s disease (almost two-thirds of Americans living with Alzheimer’s are women, according to the Alzheimer’s 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’s 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.
The grant allows Ghezzi to explore women’s health, a topic she believes does not get enough research. The structure of the grant, she says, “is an expression of the trust they give to the researcher. It funds freedom.”
Second NIH Grant Will Help Advance 3D Tissue Model
Ghezzi’s 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.
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.
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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’s 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’t need or even avoid oxygen hiding in the crevices – 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.
“The Holy Grail of tissue modeling is immune system modeling,” 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.
Says Roberts, “Her efforts contribute significantly to the profile of research at UMass Lowell in bioengineering and biomanufacturing and reflect our innovative approaches to solving problems at the interface of engineering and the life sciences."