Bioelectronic Innovations, Empowered by Chemistry

Bioelectronic Innovations, Empowered by Chemistry

UD Professor Laure Kayser received an NSF CAREER award to further her group’s materials science research

Whether it’s a smartwatch that can detect irregular heartbeats or a continuous glucose monitor, electronics that can interface with biology have already started to revolutionize the future of healthcare. But while the potential of these devices is far-reaching, the materials that make up future bioelectronics have to meet several different criteria — such as not causing damage or irritation to skin and avoiding toxic metals, for example.

Creating new organic, biocompatible materials that can interface with living systems is Laure Kayser, assistant professor in the Department of Materials Science and Engineering at the University of Delaware’s College of Engineering. Now, thanks to an award from the National Science Foundation (NSF), she and members of her lab will continue their fundamental research on a new class of polymers that could pave the way for future applications in human health.

The Kayser Lab specializes in designing, synthesizing and characterizing new plastics and polymers that can conduct electricity while safely interfacing with living systems. By working at the intersection of chemistry, polymer science and materials engineering, her lab is able to develop innovative design and synthesis approaches for creating new types of plastic materials.

Kayser, who holds a joint appointment in the Department of Chemistry and Biochemistry in the College of Arts and Sciences, said that what sets her group apart from others in the field of organic bioelectronics is a strong foundation in organic chemistry and their ability to make any material they want instead of only being limited to what’s currently available.

“We do modern chemistry, including chemistry that is not necessarily typically used in the field, and apply it to materials science,” said Kayser. “Because we have a background in chemistry and synthesis, we can make any material, characterize it, establish structure-property relationships and tailor it so the material can be interfaced with biology.”

Design rules for electronic highways and ionic waves

Starting in July, Kayser’s group will be investigating a new type of organic bioelectronic material. With a five-year, $654,206 Faculty Early Career Development Program (CAREER) award from NSF, her lab will study the fundamental properties of polymers that have properties inspired by living systems and also meet the criteria for being able to be incorporated into bioelectronic devices.

For this project, the lab will be studying derivatives of PEDOT:PSS. This polymer belongs to a class of materials known as organic mixed ionic electronic conductors, which have the unique ability to conduct both electrons and ions.

This is a necessary yet difficult to achieve property for bioelectronics: Typical electronic devices, such as laptops or cell phones, use electrons to transmit signals, while systems in biology, such as nerves, use ions. This difference in communication methods makes it difficult to “translate” signals from electronic devices into ones that a cell or organ can interpret.

Laure Kayser (right), an assistant professor in the College of Engineering’s Department of Materials Science and Engineering and doctoral candidate Vidhika Damani working in the lab with PEDOT:PSS, a polymer with the unique ability to conduct both electrons and ions.

Laure Kayser (right), an assistant professor in the College of Engineering’s Department of Materials Science and Engineering and doctoral candidate Vidhika Damani working in the lab with PEDOT:PSS, a polymer with the unique ability to conduct both electrons and ions.

There are also engineering challenges in creating this class of materials, Kayser explained. “There are very different design rules whether you want a material to be an electronic conductor or an ionic conductor,” she said. “For example, electronic conductors are very well ordered — like a highway for electrons to travel down. But if you want to make a good ionic conductor, ions usually like to be on a floppy, almost liquid environment, so more like a wave.”

Members of the Kayser lab, including doctoral students Chun-Yuan Lo, Vidhika Damani, Dan My Nguyen, and Elorm Awuyah, were instrumental in getting preliminary results for the proposed research. The team recently published a paper in Polymer Chemistry (which was also featured on the journal’s May 21st 2022 cover), where they determined the role of different chemical properties in PEDOT:PSS and how they could be changed to make the material more efficient in bioelectronic devices, a key finding that showcased how the group’s expertise in this field could be applied to PEDOT:PSS.

Through the CAREER award, the lab will continue studying derivatives of PEDOT:PSS to gain a solid, fundamental understanding of how to control both electronic and ionic conduction. The long-term goal is to develop design rules for fabricating bioelectronic devices with this class of materials in the future.

“Our lab’s focus is to understand deeply how chemical structures affect the electronic properties of those materials,” said Kayser. “Through this grant, we’re going to learn a lot about these materials — some of these ideas might fail, but we’ll learn something along the way.”

Materials science outreach and education

With this CAREER award, Kayser will also be leading different outreach and educational initiatives for both high school students and undergraduates.

Part of this work will include connecting with female students at local high schools. This will be done through both a materials science-focused outreach program as well as a mentorship program, where graduate students and senior undergraduate students will be paired with high school students to provide support throughout the college application process.

Researchers in Laure Kayser’s lab recently published a paper in Polymer Chemistry (featured on the May 21st 2022 cover) where they determined the role of different chemical properties in PEDOT:PSS and how they can be changed to make the material more efficient in bioelectronic devices.

Researchers in Laure Kayser’s lab recently published a paper in Polymer Chemistry (featured on the May 21st 2022 cover) where they determined the role of different chemical properties in PEDOT:PSS and how they can be changed to make the material more efficient in bioelectronic devices.

Kayser will also be working with Sheldon Hewlett, an assistant professor who leads instruction and teaching in the materials science and engineering department, on integrating research into undergraduate curriculum. With support from the CAREER award, junior year materials science students will conduct a polymerization of PEDOT:PSS, including synthesis, purification and characterization, as part of a laboratory module. There will also be opportunities for students to address additional research questions during the course module, as well as funded research programs for those who are interested in carrying their work into the summer.

Along with introducing students to the process of polymerization, Hewlett added that this project will allow students to work with a class of materials in a laboratory course that they are likely to encounter in their career. “Not only will this award give us an opportunity for students to do real research, but it also provides students with a novel material system to work with,” said Hewlett. “You don’t see a lot of lab courses working with these polymers at this level — of making a material from start to finish, and then characterizing it afterwards.”

Making new discoveries through ‘great fundamental science’

“Chemistry will be central to the discoveries that Laure Kayser’s research group will advance on plastics and other polymeric materials through this NSF CAREER award,” said Joel Rosenthal, professor and chair of the Department of Chemistry and Biochemistry. “Rather than simply tweaking or studying materials that already exist, the Kayser lab is adept at leveraging synthetic chemistry to discreetly control the composition, and by extension, the properties of new polymers for various applications, including bioelectronics. I’m incredibly excited to see how her group’s work will continue to develop over the next several years.”

Joshua Zide, professor and chair of the Department of Materials Science and Engineering, added, “Professor Kayser is a fantastic contributor to the Materials Science and Engineering Department, and we are lucky to have her. Her research translates the chemistry to myriad important applications, and the perspective she brings is a huge benefit to the whole department.”

While Kayser is excited about the potential of her research to potentially impact a wide range of applications and fields, she is also looking forward to the “great fundamental science” that this CAREER award will enable her group to do.

“It’s a relatively hot area that is going to continue growing, so it’s a good place for us to be leading the pack,” she said. “I’m hoping that by learning more about the fundamentals of these materials, it might inspire others to explore different molecular designs and how they can be translated into devices. Overall, I think we’re going to make lots of really cool discoveries.”

| Photos by Evan Krape |

The TuFF Age

The TuFF Age

UD researchers tackle new task in making complex material more viable for building aircraft

TuFF — Tailored Universal Feedstock for Forming — is a strong, highly aligned, short-fiber composite material that can be made from many fiber and resin combinations. Created at the University of Delaware’s Center for Composite Materials (CCM), it can be stamped into complex shapes, just like sheet metal, and features high-performance and stretchability up to 40%.

Since its introduction, CCM researchers have explored applications for TuFF, from materials for repairing our nation’s pipelines to uses in flying taxis of the future.

Now, armed with $13.5 million in funding from the U.S. Air Force, UD mechanical engineers and co-principal investigators Suresh Advani and Erik Thostenson along with industry collaborators Composites Automation and Maher and Associates are working on ways to improve manufacturing methods for TuFF.

“I am really excited at the opportunity to mature the TuFF pre-pregging process and demonstrate high-throughput composite thermoforming for Air Force relevant components,” said David Simone of the U.S. Air Force.

The goal is to enable lighter-weight composites to become cost-competitive with aluminum for creating small parts found in air vehicles.

Advani explained that when it comes to making aircraft materials more cost-efficient, reducing a material’s weight even a mere kilogram, just 2.2. pounds, will reduce fuel consumption and emissions and can result in thousands of dollars in savings over time.

This is because aircraft are heavy. A Boeing 747, for example, weighs a whopping 404,600 pounds. A B2 Stealth Bomber in the U.S. Air Force, meanwhile, tips the scale at over 43,000 pounds.

“In general, the aerospace industry wants to reduce weight and replace metals,” said Advani, George W. Laird Professor of Mechanical Engineering. TuFF is a good option because the material can achieve properties equivalent to the best continuous fiber composites used in aerospace applications.

Advancing TuFF thermosets

Until now, most of the work around TuFF has focused on thermoplastic composite materials that melt when heated, becoming soft and pliable, which is useful for forming. By contrast, TuFF thermosets have a higher temperature threshold, making them useful for aerospace applications. But TuFF thermosets have manufacturing challenges, too, including the long manufacturing times necessary to make a part.

In this new project, Thostenson and Advani will work on ways to improve the viability of thermoset TuFF composites. To start, the researchers will characterize the starting materials’ mechanical properties to understand how to make TuFF thermosets reliably and consistently. The research team will explore whether they can make the material in a new way, using thin resin films and liquid resins. They will test the limits of how the material forms and behaves under pressure and temperature, too.

“How does it stretch during forming in a mold? What shapes can we make? When does it tear or thin or develop voids that can compromise material integrity?” said Advani.

Having a database for such properties and behaviors will be useful in understanding TuFF material capabilities and limits, and to inform efforts to model and design parts with TuFF.

Thostenson, professor of mechanical engineering, is an expert in structural health monitoring of materials. He will advance ways to embed sensor technology into TuFF thermosets. This would allow the researchers to see from the inside how the material is forming and curing during its manufacture, in hopes of being able to gauge—and improve— the material’s damage tolerance.

It’s intricate work. To give you an idea of scale, a single layer of TuFF material is approximately 100 microns thick, about the diameter of the average human hair. The carbon-nanotube sensors Thostenson plans to integrate into the material are smaller still—one billionth the width of a human hair.

“This would allow us to do health monitoring for the materials and parts during service life, but you could also imagine using sensor technology to detect a defect during manufacturing,” said Thostenson.

While it remains to be seen whether this is possible, Thostenson said having this ability could result in real cost savings for manufacturing methods, where real-time knowledge of how a material is curing could help the researchers speed up production. Additionally, if there is a material failure, such as a tear, the sensors could point the researchers where to look in the process.

The research team also plans to develop a virtual modeling system to refine the material-forming process through computer simulation instead of by trial and error. In this way, the team will better understand each step in the material-forming process, enhancing the team’s ability to make TuFF materials consistently and reliably — a must for aerospace applications.

“I am hoping this work will allow us finally to make composites cost competitive with the metal industry,” said Advani.

In addition to Thostenson and Advani, the team includes, from CCM, Jack Gillespie, Dirk Heider, Shridhar Yarlagadda, Thomas Cender, John Tierney and Pavel Simacek, along with four to five graduate students.

Fine-Tuning Touch Technology

Fine-Tuning Touch Technology

UD’s Charles Dhong gets $1.9 million to develop new tactile aids

Bumps and lines make up touch-based technology such as Braille. But the human sense of touch is keen enough to detect differences that are much smaller. Research by Charles Dhong and his group at the University of Delaware has found that humans can feel differences in the chemical composition of a surface, down to the substitution of a single atom.

That ability is one focus of Dhong’s work as an assistant professor in the Department of Materials Science and Engineering and the Department of Biomedical Engineering at UD. He explores new possibilities for tactile technologies and the mechanical forces that affect the perception of touch.

Dhong presented research on this at the American Chemical Society’s national meeting in San Diego on Wednesday, March 23. And he and collaborator Jared Medina, associate professor in UD’s Department of Psychological and Brain Sciences, have new support for development of higher-quality tactile aids for people with visual impairments. The $1.9 million grant, which started in February and continues for five years, is from the National Eye Institute in collaboration with the National Federation of the Blind.

Current technology recreates tactile sense using tiny motors and electricity. But the bumps and buzzes they generate are not that good at mimicking the real thing.

A new approach to controlling perception of texture could have many applications, Dhong said. It could make it possible to design new types of surfaces or provide improved integration of the sense of touch into virtual reality environments. It could also improve existing devices, such as Braille displays, or provide feedback to surgeons conducting surgery remotely.

“When you touch an object, you’re feeling its surface, and you can change how it feels by changing the friction between that surface and your finger. That’s where the chemistry comes in,” Dhong said. “We think materials chemistry could open the door to recreating more nuanced sensations, whether you’re designing a product to feel a certain way or creating feedback devices for virtual reality.”

Research by Charles Dhong and his group at the University of Delaware has shown that humans can feel tiny differences in a surface, down to the substitution of a single atom.

Research by Charles Dhong and his group at the University of Delaware has shown that humans can feel tiny differences in a surface, down to the substitution of a single atom.

Progress in touch technology has lagged, in part because it involves multiple types of sensations, such as temperature and pain. In addition, some efforts to recreate touch have included systems designed to simulate a sense of moving one’s body — a complex sensation.

Dhong’s research focuses on a specific type of touch: using the fingers to detect fine textures. Some methods for evoking this kind of fine touch are already available. Your smartphone attracts your attention without sound, using a tiny vibrating device within. A refreshable Braille display for people with low vision or blindness uses an actuator to move pins up to create bumps.

This type of touch depends on a physical force — friction — which is the resistance that skin encounters as it brushes against an object. While attributes such as the contours of a surface influence friction, so does chemistry. The structure of the molecules within a substance and the properties of its surface also influence the sensation.

Dhong and his colleagues suspected that by altering only chemistry-related features, they could change how a surface feels.

In previous work, Dhong’s team asked people to touch single-molecule-thick layers of silane, a silicon-containing compound. None of the silane surfaces possessed detectable differences in smoothness.

But those who touched the surfaces could differentiate them based on chemical differences, including the substitution of one atom within each silane molecule for another, because of subtle changes in friction.

“Recent research has shown that people can detect the physical differences between surfaces at a resolution as low as 13 nanometers,” Dhong said. “Now we are saying that the sense of touch can also identify chemical changes as small as swapping a nitrogen atom for a carbon atom.”

In San Diego, Dhong presented recent work focusing on polymers, the go-to molecules for synthetic materials. Polymers are distinguished not only by their chemical formulas, but also by a characteristic known as crystallinity, which describes how neatly the chain-like molecules are organized. The polymers in these experiments had identical formulas and molecular weights. Only the degree of crystallinity differed.

In their experiments, the researchers focused on the perceived texture of thin layers of polymers. As with the silanes, they asked the subjects to slide their fingers across the polymer. This time, too, they found that people could differentiate between the polymers based only on variations in the friction resulting from subtle changes to the crystallinity of the molecules.

About the researcher

Charles Dhong, assistant professor of materials science and biomedical engineering in the College of Engineering, joined the University of Delaware faculty in 2019.

He earned his bachelor’s degree in chemical and biomolecular engineering at the University of California, Berkeley, his doctorate at Johns Hopkins University and did postdoctoral research in nanoengineering at the University of California, San Diego.

His research focuses on understanding the mechanical forces that shape the human sense of touch.

 Photo | illustration by Christian Derr, photo by Maria Errico, image of hand courtesy of Charles Dhong

Tackling the Plastics Problem

Tackling the Plastics Problem

Collaborative project aims to find sustainable ways to create, destroy plastics

Despite the society-changing improvements that plastic materials have brought to humanity, there’s no question that they also present us with new challenges regarding what to do with the large amounts of plastic waste we generate, from the oil-based chemicals used to create products to the microplastics found everywhere after plastics breakdown in the environment.

Finding a solution to plastics pollution that will work in the lab and in the real world will take a diverse team of innovative individuals with expertise that transcends the incredible talent found at the University of Delaware. That’s why researchers from UD’s College of Engineering and Biden School of Public Policy and Administration are joining forces with experts at the University of Kansas and Pittsburg State University.

“The practices by which society works now are really not sustainable,” said Raul Lobo, Claire D. LeClaire Professor of Chemical Engineering and associate department chair in UD’s Department of Chemical and Biomolecular Engineering, who is leading the research effort for UD. “We need materials that minimize our dependency on fossil fuels and that allow consumers to recycle plastic products efficiently and with ease.To this end, the UD-KU team will develop new molecules that can be used to make a new generation of environmentally friendly plastics.”

Raul Lobo, Claire D. LeClaire Professor of Chemical Engineering and associate department chair in UD’s Department of Chemical and Biomolecular Engineering, is leading the research effort for UD in collaboration with experts at the University of Kansas and Pittsburg State University to find sustainable ways to create new plastics and more efficiently reuse them.

The National Science Foundation’s Experimental Program to Stimulate Competitive Research has awarded the group $4 million in funding to do just that. About $1.4 million of that funding will go to UD to support this vast research effort to develop processes to transform “biomass,” such as agricultural byproducts, into commercially viable plastics materials and to chemically deconstruct such plastics effectively and efficiently so that they can be recycled and reused.

UD faculty members on the team include Professor Hui Fang with the Department of Electrical and Computer Engineering, Professor Kalim Shah with the Biden School and Department of Chemical and Biomolecular Engineering Professors Marianthi Ierapetritou, Lobo, Marat Orazov and Dionisios Vlachos.

Lobo, who also holds a joint professorship in the Department of Materials Science and Engineering, said the project will focus on developing polymers that behave like polyethylene terephthalate, or PET, a very common type of plastic found in consumer products such as water bottles, fleece and food-wrapping film. A polymer is a very long molecule, such as proteins, starch or DNA, that is built of repeated building units, like the adenine (A), guanine (G), cytosine (C) and thymine (T) in DNA molecules. Different polymers form by knitting together different building units. Once they are sufficiently long, they can be easily melted, shaped or molded, and solidify upon cooling

“We have ideas of polymers we think will make materials that are better than PET in a number of ways,” Lobo hinted. “Now, we have to prove it.”

From Biomass to Building Blocks

The goal is not only to find new materials with good and useful properties, but to do so using molecules with building blocks that come from biomass (and not fossil fuels like oil) and that are designed to be recyclable.

“We’re trying to make this society more sustainable by developing technology that has the potential to be practical,” Lobo said. “The material we’re trying to make … looks like the plastics we use today, but comes from biomass.”

This graphic illustrates the flow of a “circular economy,” as opposed to the “linear economy” of the U.S. In a circular economy, products are produced, consumed and reused so that there is little or no waste leftover during any of those processes.

For example, plants also produce sugars with fewer carbons than the sugar that we eat, and those sugars and their derivatives could be used as building blocks for plastics. The material has to be stable just enough, and strong enough, to hold up in another life as, say, a plastic bag. By focusing on biomass that’s not edible and not toxic — think of stalks from corn or leftover parts from harvested sugar cane — researchers will try to prepare new building blocks for plastics such that they don’t compete with food sources, do not depend on fossil fuels and can be easily assembled and reassembled.

Then these engineers must figure out how to translate the science into actual societal benefit. That means also exploring the policy and economic elements associated with shifting the foundational building blocks of a product used in almost everything in our daily lives.

The practical implications of this work will certainly relate to cost. Six decades of experience making PET and using it in multiple products means six decades of being able to find cost efficiencies along the way. It will still take some time for any new building blocks that could replace PET, even if they are superior in performance and for the environment, to find all possible efficiencies and cost savings.

Over the next four years, up to five UD graduate students will play a role in this interdisciplinary research, from the machine learning that will be used to explore existing research literature and gaps in knowledge, to the chemistry of the components, to the economics of their application and recycling.

“There’s a vast amount of information there,” said Hui Fang, an associate professor with the Department of Electrical and Computer Engineering. “We’re trying to develop a machine learning-based technique that can first extract information automatically from the literature and then allow the researchers to see what’s missing.”

From Wastefulness to Sustainability

With so much waste in the world — up to one-third of the food resources produced are actually wasted — it would be incredibly beneficial to find ways to reuse those tossed corn husks or the leftover fibers from sugar cane, particularly as we try to avoid 1.5 degrees Celsius of atmospheric warming due to greenhouse gas emissions. At the United Nations Climate Change Conference in Glasgow, experts emphasized that exceeding that level of warming will not only be catastrophic, but will be impossible if world nations cannot curb their reliance on fossil fuels.

The idea of a “circular economy,” in which products are produced, consumed and reused — as opposed to the “linear” way the world currently produces, consumes and trashes most products — could literally be that change the world needs. From the molecular beginnings of plastic products, energy is used and waste created. But is it possible to reduce this amount of energy and could the waste be reused in another production process?

Dionisios Vlachos, Unidel Dan Rich Chair in Energy Professor of Chemical and Biomolecular Engineering, director of the Catalysis Center for Energy Innovation and director of the Delaware Energy Institute, is exploring how to make new building blocks for plastics from current waste streams.

“We’re thinking about how we can take the waste stream and make new building blocks,” said Dionisios Vlachos, Unidel Dan Rich Chair in Energy Professor of Chemical and Biomolecular Engineering, director of the Catalysis Center for Energy Innovation and director of the Delaware Energy Institute. “This is a global issue.”

Today, most plastics (and many of the other products we consume daily) are created from petrochemicals. Most plastics are not easily recycled because once they’re broken down into their original pieces, they are difficult to put back together again and so they ultimately end up as waste. UD’s investigators are in pursuit of novel chemicals that can be easily manufactured from biomass and that not only make outstanding plastics, but also could, with little effort, be transformed into raw materials for new plastic products.

“If we don’t take action today, things will be really bad in the future,” Vlachos said. “There are many waste streams with multiple societal health problems. They have to be addressed at a global scale. If we’re making renewable plastics, it would be great, but it’s just part of the story.”

A Holistic View

While some on the team will focus on the chemical engineering of the molecules themselves, Ierapetritou and her team will be analyzing those new materials for their potential environmental impacts, economic costs and whether the new product would be practically scalable from a small lab to a commercialized solution.

In this project, Bob and Jane Gore Centennial Chair of Chemical and Biomolecular Engineering Marianthi Ierapetritou and her team will be analyze proposed new materials for biorenewable plastics for potential environmental impacts, economic costs and feasibility.

“Of course, this goes back to changing the culture of people or introducing different policies, which is one of the things we’re hoping to investigate,” said Ierapetritou, who is the Bob and Jane Gore Centennial Chair of Chemical and Biomolecular Engineering at UD. “But you need policies, you need incentives to make the change that needs to be made.”

What they’re aiming to create may be expensive — possibly too expensive to compete without incentives. But even if some of the new material was used in plastics production, it could still help reduce the pollution associated with creating a product made with 5% or 10% biomass-sourced plastic, said Lobo.

“Our scientific and engineering folks say they can do this in the lab, and they can scale it up. But where is the acceptance or adoption of it?” said Kalim Shah, an assistant professor at the Biden School of Public Policy who will be exploring the economic and environmental implications of a substitute for plastics and its potential in real-world markets.

“I think there’s a real awareness now of linking the disciplines that we’re very well known for at UD — chemistry and chemical engineering — to the policy and macroeconomic business aspects of the problem,” he said. “I’m really happy to have colleagues that are willing to include my perspective and take a multidisciplinary approach to us to move forward together.”

Kalim Shah, an assistant professor at the Biden School of Public Policy, will look at the economic and environmental implications of a proposed biorenewable substitutes for plastics.

If they find the solutions they believe exist, it would still take years before a plant capable of making thousands of tons of polymers goes online. The biomass-sourced building blocks could also be a boon for farmers and companies that work with the agricultural products that could become future plastics.

There’s also the potential they could create something even better: a biosourced plastic that can last longer or require less material.

Their work will also closely examine how to deconstruct these new polymers so that it can be a truly recyclable product. Lobo said he had no doubt they could succeed on that front. But whatever they uncover, they will publicize their findings and make them available to other researchers.

“If we succeed, we might be able to reduce, to some degree, the quantity of plastics or the amount of oil we consume,” Lobo said. “There are chemical reasons why some polymers have these good properties but others don’t. Based on that information, we’re going to eventually be able to provide better products for society. That’s what engineers do.”

 Photos by Evan Krape, Lane McLaughlin and iStock | Image courtesy of Dionisios Vlachos | 

Improving Human Health

Improving Human Health

UD’s Xinqiao Jia secures $4.85 million to advance vocal fold, salivary gland research

University of Delaware materials scientist Xinqiao Jia has received a combined $4.85 million in funding from the National Institutes of Health (NIH) for research aimed at improving human health through new approaches in tissue engineering.

Tissue engineering is an interdisciplinary field that focuses on developing methods to repair or replace biological tissues that have been damaged or degraded over time.

Jia and colleagues will explore ways to regenerate salivary glands that have been damaged by radiation therapy for head and neck cancers. She also will focus on understanding what causes damage or scarring to vocal folds, the pliable tissue that enables our ability to talk.

Faster than a hummingbird’s wings

Vocal folds produce sound by vibrating more than 100 times per second as air from the lungs passes through the paired tissues. In other words, our vocal folds do the heavy lifting when we speak.

For comparison, this movement is nearly two times faster than the average North American hummingbird, which flaps its wings about 53 times per second in flight.

Each vocal fold consists of a soft connective tissue, known as the lamina propria (LP), sandwiched between a muscle and a flat, protective layer called the epithelium (EP). It’s a delicate structure, and little is known about the molecular and cellular processes that can lead to chronic vocal fold scarring, leaving millions of affected Americans with limited treatment options.

Armed with $2.49 million in NIH funding, Jia, professor of materials science and engineering in the College of Engineering, will spend the next five years working to understand how vocal folds regenerate after damage — or don’t — and why.

“If you have a scar or scab on your skin, eventually it just falls off. But on a vocal fold this scarring persists and doesn’t go away. With scarred vocal folds, your ability to speak is severely compromised,” she said.

Jia is particularly interested in whether vocal fold damage results from chemical (i.e., smoking) or mechanical causes to drive development and testing of new treatment options.

Building on previous research, she plans to create a vocal-fold-on-a-chip model with embedded sensor technology to monitor the development of the vocal fold tissue in real time with help from several interdisciplinary colleagues. UD collaborators include Joe Fox, a pioneer in developing highly efficient chemical reactions for making tissue-mimicking hydrogels used to grow the vocal folds, and materials scientist Charles Dhong, who specializes in measuring mechanical forces at biological interfaces. Susan Thiebault, who has expertise in vocal fold physiology and biology at University of Wisconsin, Madison, also will contribute to the project.

The model will include built-in airflow to stimulate speech, allowing the device to reflect the human anatomy and physiology more closely than current models. The researchers also plan to introduce cigarette smoke into the chip model to explore whether smoking plays a role in the damage that can cause vocal-fold tissue to become stiff and fibrotic.

“Once our model is validated, we can begin testing medications for repairing the tissue,” Jia said.

Help for dry-mouth syndrome

Meanwhile, in a second project with $2.36 million in NIH funding over five years, Jia and colleagues will investigate methods to restore function in salivary glands that have been damaged by radiation therapy for head and neck cancers.

The human body contains three major salivary glands. When these salivary glands become damaged, they no longer secrete the saliva needed for digestion and for keeping the mouth free of bacteria. This can lead to a condition called dry-mouth syndrome, or xerostomia, a permanent and painful side effect of radiation therapy that affects about 50,000 head and neck cancer patients annually in the United States.

Jia explained that it is acinar cells that are responsible for creating saliva, which is collected in the ducts and channeled to the mouth. While the acinar cells become damaged after radiation treatment, the channels remain largely intact. Interestingly, within these salivary gland channels are progenitor cells that have the potential to become different cell types and restore the salivary gland.

In previous work, Jia and colleagues including Dr. Robert Witt, director of the head and neck oncology clinic at ChristianaCare’s Helen F. Graham Cancer Center, showed that it was possible to isolate progenitor cells from salivary gland tissue samples taken prior to radiation therapy and grow them in hydrogels in the lab into multicellular structures that mimic the structure of acini that secrete saliva. While this advance is hopeful and exciting, the hard part has been figuring out ways to reintegrate the tissue in the body.

For the new arc of this work, Jia enlisted several researchers with expertise in needed areas to join the team, including Fox and Jason Gleghorn, a biomedical engineer. Gleghorn’s background in the biological processes that cause organs, such as the lungs, to develop a branched architecture and in developing artificial blood vessels will be useful in the context of salivary gland regeneration, Jia said. In the meantime, Fox’s chemistry expertise can help provide the cells with the proper environment so that they organize and orient correctly to do their job. Kenneth Yamada, a biologist with the National Institutes of Dental and Craniofacial Research with extensive background in the developmental biology of salivary glands, rounds out the team.

“One thing we’ve learned from literature and our previous study is that the salivary gland doesn’t develop if there is no nerve or blood vessel,” said Jia. “In this new work, we plan to reconstitute blood vessels alongside the growing salivary gland in hopes the vasculature will provide the right signal and architecture to guide the development of the salivary gland. It’s going to be very difficult, but you have to start somewhere.”

| Photo by Evan Krape