University of Virginia: Research To Replicate Human Tissue Earns A Half-Million-Dollar Grant

Rachel Letteri digs polymers because, in them, she sees so many possibilities.

“Polymers are big molecules that string together many different building blocks and play so many important roles in medicine and engineering,” said Letteri, an assistant professor of chemical engineering at the University of Virginia School of Engineering and Applied Science.

“Big” here is relative. Even the largest molecules, of course, are tiny, invisible to the naked eye. But to a chemical engineer like Letteri, polymers can be quite hefty.

This compiling of single-molecule building blocks into “big” macromolecules designed to do a job – either by nature or by people – is ubiquitous. Polymers are in everything from the foods we eat to plastic grocery bags. Letteri’s lab is designing polymers for use in health care, such as repairing tissue loss from injury or disease.

“If we can build these materials using all the possibilities that the chemistry of big molecules gives us, we can get closer and closer to mimicking natural tissue so we can guide cell growth for therapeutic applications,” Letteri said.

Her research is so promising that the National Science Foundation has granted her a five-year, $564,000 award to see where she can take it. The money is part of the foundation’s prestigious CAREER Award program for early-career faculty, which recognizes the recipients’ potential for leadership in research and education.

Letteri’s materials are made by attaching protein fragments called peptides to the ends of polymers and mixing them together in water to form a hydrogel – a clear, Jell-O-like substance. The peptides are akin to Velcro strips that bind polymers to form the material. By making small adjustments to the chemistry of the peptide Velcro strips, Letteri’s team can design the resulting hydrogel to mimic the physical properties of living tissue.

“The chemistry is just so creative and boundless,” Letteri said. “Because these molecules are so big, we have so many more knobs that we can tune.”

Doctoral student Israt Jahan Duti is leading the lab work. Duti, who arrived at UVA around the same time as Letteri in 2018, helped build Letteri’s lab and has done much of the experimentation and data collection for the CAREER Award project, titled “Peptide stereocomplexes as dynamic junctions in polymeric biomaterials.”

Duti fabricates the hydrogels and alters the peptide Velcro strips to adjust how stiff or soft the material is, whether it’s elastic or liquid, and how long it lasts before the body’s proteins start breaking it down.

“We use peptides because cells can recognize them and because of their structural and functional diversity,” Duti said. “You can change their sequence, their structure, their charge. These are very small changes, but each has a big effect on the material’s properties, which is pretty cool.”

Controlling how long the hydrogel will last in biological environments is a primary objective of the project. In some cases, you want the material to disintegrate to allow cells space to grow; in other cases, you want the hydrogel to remain stable longer as support for the cells encapsulated in the material.

Letteri’s goal is to build a system for producing hydrogels that capture the complex features of natural human tissues. The lab’s materials and methods will be available to other researchers who need customized biomaterials to conduct cell culture studies, 3D-printing-based biomanufacturing, tissue regeneration and related biomedical research.

From her first day at UVA, Letteri has had an energetic team of graduate and undergraduate researchers helping establish her lab. The group has become an integral contributor to the Department of Chemical Engineering’s strength in biomaterials research, which has already yielded collaborations with colleagues both within the department and in UVA’s School of Medicine.

“I am incredibly grateful to be building a lab with an absolutely phenomenal group of researchers,” Letteri said. “They are enthusiastic, creative and share a commitment to strong science, safety, education and mentorship.”

“Rachel’s drive to push improvements in her research field was obvious when she interviewed,” William Epling, chair of chemical engineering, said. “I knew this CAREER Award was just a matter of time for her. I see her being a leader in biomaterials engineering for a long time, and because she’s equally committed to teaching, her impact on our students, department and profession will be far-reaching.”

Letteri chose to study chemical engineering as an undergraduate at the University of Notre Dame for much the same reason she loves working with polymers: so many possibilities.

“I tell students chemical engineering gives us useful tools to understand and solve problems in the world around us,” said Letteri, who thought she’d apply her doctoral education in industry before discovering she enjoyed teaching as much as research.

“We know how heat moves, how materials move and how reactions occur, and the driving forces behind all of this. It’s exciting that with one set of skills, you’re really well-equipped to address problems that range from medicine to renewable energy.”

Letteri’s teaching debut at UVA was Material and Energy Balances, the first engineering course undergraduates take as chemical engineering majors. Her students nominated and championed her for the UVA Trigon Engineering Society’s Thomas E. Hutchinson Award. No first-year faculty member had won the teaching award before.

Letteri said she wasn’t always a strong student, but beginning in high school, excellent teachers and mentors encouraged her curiosity and took chances on her.

As an undergraduate, she discovered lab research made her a better student. To make an experiment work, she had to understand the chemistry or math or physics at play.

The work helped connect concepts learned in the classroom to what she saw happening in the lab, and kindled curiosity, she said. Graduate school cemented her path in research, but she also found new passions for writing, teaching and mentoring.

The influence of undergraduate research on her own approach to learning and her career trajectory inspired the educational outreach portion of her CAREER Award project. She plans to improve first- and second-year students’ engagement in undergraduate research at UVA and at Prairie View A&M, a historically Black university in Texas. Letteri is partnering with her friend and colleague at Prairie View, assistant professor Marco Giles.

“It starts with students learning how to ask questions like an independent researcher, then learning new techniques and learning them well enough to teach them,” Letteri said. “I think it improves classroom performance, and success generally, for undergraduates to have really good research experiences.”

Each summer, a Prairie View student will work in Letteri’s lab to attach peptide Velcro strips to the snowflake-like polymers they develop in Giles’ lab during the school year. Through collaborative research bridging the Giles and Letteri laboratories, the researchers want to learn how polymer topology, or configuration, affects the properties of hydrogels constructed from the peptide Velcro strips.

“Undergraduate research and education as well as the supportive polymer materials communities were essential in inspiring and supporting my development in a career I love,” Letteri said, “I can’t wait to pass these opportunities and networks on to our UVA students – future leaders in the field.”