Junior Alejandro Wiltshire has been interested in conducting research for as long as he can remember. Now he works in the Biological Soft Matter Mechanics Laboratory (BSMM) with Guy German, associate professor of biomedical engineering.

“I think of it as a skin lab, even though it’s more than just that,” Wiltshire says. “It’s a very versatile biomedical engineering lab. Most of the time when people think of biomedical engineering, they think of cells or creating some sort of vaccine, whereas this is the more mechanical aspect of it. It’s a great place to learn about skin and to learn about a different aspect of mechanical engineering.”

Wiltshire joined the lab his freshman year. With German’s guidance, he has refined his skills in research and laboratory methods.

“Alejandro is committed, rigorous, and an asset to my team,” German says. “He has integrated well with my team of graduates and undergraduates, has learned the varied techniques required for his research quickly and efficiently, and has shown me he can perform effectively independently and as part of a team.”

Wiltshire is part of two research projects. His work on the rate of infection resulting from surgical sites has broad implications in helping regions of the world where infection rates are higher than average.

“If we can figure out how bacteria enters wounds, we can hopefully prevent this from happening,” Wiltshire says. “We are hoping that through this research, we can actually improve the pre-operative procedures, in order to lower the rate of surgical site infections.”

Wiltshire examines the rate of bacterial infection by making observations through imitation. Using a powerful microscope, Wiltshire shared images of his biomechanical model in detail. A substrate plays the role of the skin, while fluorescent beads mimic bacteria.

He included visuals in the demonstration, which allowed for a deeper, more comprehensive understanding of his investigation.

“I think a lot of science is visuals, like you need to see it in order to understand it,” he says. “I’m more of a visual learner myself, so I like to show things and explain along the way.”

Wiltshire’s second project relates to wrinkle formation as a result of aging. Using a series of complicated instruments, Wiltshire works to determine the individual mechanical and structural properties of skin and how this relates to the formation of wrinkles.

The experiments use skin samples from human cadavers. Within four to six days, members of the lab conduct rigorous experimentation on the samples to gain a better understanding of how wrinkles develop over time and how collagen fibers in the skin alter the shape of the wrinkles.

As a member of an artistic family, Wiltshire knew his interests differed greatly from the people around him, but that didn’t deter him from finding a balance between his love for engineering and his appreciation for art.

“I try to take everything in my life and tie it together,” says Wiltshire, who grew up in Hempstead on Long Island. “I think my purpose was kind of trying to tie the things that I enjoy in science and STEM with the artsy side of my life and the things that I view as being artsy.”

Through his position as the STEAM chair of the Binghamton Art Club, Wiltshire hopes to bring awareness to the intersection of art and engineering, and encourage students to pursue and enjoy both paths.

Wiltshire says his experiences in the lab, including a project as part of the Summer Scholars and Artists Program in 2022, have improved his understanding of complex concepts in his undergraduate engineering classes.

“I’m not a classroom learner, I’m more of a hands-on learner,” he says. “So I’ve realized that the more time I spend in the lab, the more that I actually learn here and that I can apply it to the classroom as opposed to the other way around.”

Wiltshire hopes to pursue a doctorate in biomedical engineering at Binghamton after he graduates.

“I’m always investigating something that I didn’t know before,” he says, “and that, to me, is what I want to do.”

“The AHA is such a big and well-respected organization, so it is a nice validation to see that they value my research and ideas,” says Weiss, a biomedical engineering doctoral student who received a competitive two-year pre-doctoral fellowship.

Weiss conducts her work in the lab of Tracy Hookway, assistant professor of biomedical engineering. The team uses cell culture, 3D modeling of stem cells and live imaging of tissue for regenerative medicine therapy.

“Natalie has been a huge asset to my lab,” Hookway says. “She’s incredibly intelligent and very ambitious, and she’s not afraid to ask questions.”

Weiss’ research involves creating working models of human hearts and then testing various drugs and therapies with the goal of resolving or improving cardiac fibrosis. She uses stem cells derived from human skin to make heart muscle cells and then combines them with proteins, sugars and a gel polymer, which is then piped into a 3mm donut ring mold (of sorts). The process takes about a week and a half, but once the cells are added to the mold, the ring forms overnight into a simplified, beating human heart model.

“By testing on these models, it saves time, money and testing on animals,” Weiss says, adding that she often has 40 rings going at a time. “What I’m hoping to do, once the models are a little more advanced, is replicate the stiffness of cardiac fibrosis in the model and then test a couple of drugs and see if it responds in a positive way.”

As a high school student in East Meadow, Long Island, Weiss knew she was interested in the medical field. She volunteered in an emergency room and got her EMT certification.

“I’ve also always loved problem solving — taking things apart and figuring out how they worked,” she says. “I wasn’t aware I could put those two interests together until a biomedical engineering major kept popping up again and again as I was researching college programs.”

She received her undergraduate degree in biomedical engineering at Stony Brook University in 2019, and then started her graduate career at Binghamton that fall. She selected the program because she was impressed with Hookway, who would become her advisor.

“I wanted someone who I can connect with,” Weiss says. “Dr. Hookway really seemed like someone who would advocate for her students, so I knew she was going to care about my progress and help me out.”

Once Weiss completes her doctorate, she hopes to complete a post-doctoral fellowship and then become a professor and run her own research lab.

Fake “Frank” Lu, an assistant professor of biomedical engineering, uses stimulated Raman scattering (SRS), a molecule identification technique, to develop a multicolor imaging technology for brain cancer pathology during surgery.

A three-year, $750,000 R00 grant from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) supports his research at Binghamton.

There are two steps to get rid of a brain tumor: removing the literal mass and then removing the lingering cancer cells at the edges. Removing the lingering cells can be tough, requiring evaluation to avoid destroying functioning brain structures.

Cancer cells are denser than normal cells, which helps them to be identified. Modern procedures involve a pathologist standing by for intraoperative consultation, using neuronavigation systems (such as an MRI scan) or fluorescence imaging to detect lingering cancer cells. Each of these techniques has drawbacks:

• With intraoperative staining-based histopathology, tissue samples are taken and evaluated in a nearby laboratory. Although accurate, this is ultimately a slow process, only allowing three samples to be evaluated during surgery.
• Neuronavigation systems can also be flawed as a result of the brain moving during the surgery, which is called “brain shift.”
• Fluorescence imaging uses fluorescent dyes to label and locate the cancer cells. Unfortunately, this is a messy process and isn’t accurate at distinguishing the margins of the tumor.

Lu’s technology is label-free, rapid and detailed. He expects that in the future, SRS can be used to evaluate 20-30 tissue samples during surgery to help delineate the tumor margin.

SRS detects “molecular fingerprints” by exciting the chemical bonds in molecules and reading the frequencies emitted by the vibrational states of the bond. This information is then used to assign different colors to the molecules, allowing for a detailed image.

Lu has also improved SRS so that it can create images of lipids, fatty acids that he says are important markers for the presence of cancer cells. Axons, the long, thread-like sections of nerve cells, are wrapped in lipid layers called myelin sheath. In areas affected by cancer, they break down, leaving lipid droplets that can be easily detected by Lu’s technology.

Lu envisions the technology being incorporated into a machine for operating rooms, and he is debating two options: a handheld probe to create images of the internal cavity, or a device that creates images of tissue samples from multiple locations. “We are providing a tool that is complementary to the current neuronavigation system,” he says.

The next step is to collect more data to solidify the efficiency of the technology. Lu is collaborating with SUNY Upstate Medical University and Brigham and Women’s Hospital to get larger data sets.

Eventually, Lu would like to implement machine learning into the technology for faster and more efficient diagnosis. He also hopes to apply this technology to other types of cancer diagnosis and even other neurological diseases, including Alzheimer’s, and do more work in live cell imaging.

Before joining Binghamton’s faculty in 2017, Lu completed a post-doctoral fellowship at Brigham and Women’s Hospital and Harvard Medical School, where he collaborated with cancer pathologists, surgeons and researchers to transform this technology. He also secured a prestigious NIH K99 Pathway to Independence Award, which is designed to facilitate researchers’ transitions from post-doctoral work to independent tenure-track jobs.

“Everyone contributes to the technical development of this technology, [but] Frank’s definitely the driving force behind the work,” says Sandro Santagata, a neuropathologist and assistant professor at Harvard Medical School and Lu’s post-doc collaborator. “He’s a team player, which is very important in scientific research.”

Lu, who was born in Shandong, China, received an undergraduate degree in optoelectronics from Zhejiang University in China and a graduate degree in bioengineering from the National University of Singapore.

He eventually realized he wanted to move toward healthcare applications of photonics rather than pure engineering and technology, which led him to Raman bioimaging. “For me, pure engineering work was not that exciting,” Lu says. “Later in my career I started thinking about practical applications of biophotonics in life science.”

As a kid, Lu was always tinkering, even attempting to develop a FM radio and an electric generator. Ever since, he has been on course to create innovations that would benefit society.

“To be successful in science requires a pretty remarkable drive,” Santagata says, “and he’s got it.”

“Skin acts as a physical, chemical and microbial barrier. It also helps regulate temperature and enables mechanoreception: the ability to sense touch,” says Guy German, an assistant professor of biomedical engineering whose research focuses almost exclusively on the body’s largest organ.

“[There is] a diverse population of microorganisms that naturally reside on your skin,” he says. “When [skin] becomes ruptured, its barrier function is lost, leaving underlying living tissue exposed to harmful pathogens. These pathogens can cause a variety of diseases and infections.”

German will continue his research into skin with a five-year, $500,000 grant from the National Science Foundation’s prestigious Early Career Development (CAREER) program. His project – “Understanding the Multi-scale Failure Mechanics of Human Skin with Age, Ultraviolet Photodamage and Bacterial Growth” – formally begins in July.

“My first reaction to learning about the award was a combination of happiness that I could support more graduate student research and excitement because the award will enable my lab to explore a new research area that I’m passionate about,” German says. “Overall, this project aims to support up to two graduate students over the five years.”

The fundamental research will explore how aging, ultraviolet light and bacteria weaken skin, cause wrinkles and increase the risk of skin rupture. The results will provide a better understanding of the biomechanical aging process, the onset of skin diseases that could be caused by bacteria in the skin microbiome, and new approaches in skin-based drug delivery in creams and ointments. Some of the results may also have applications related to flexible electronics and energy harvesting.

Much of the current work in the field focuses on macro-testing equipment and treating skin as a homogenous material, but skin is heterogeneous at many length scales, German says, so he plans to look at the tissue microscopically. Experiments will combine immunostaining, mechanical manipulation, high-speed imaging and traction force microscopy to show how skin degrades under a variety of conditions.

The National Science Foundation’s CAREER grants support early-career faculty who have the potential to serve as academic role models in research and education while leading advances in their fields. German joined Binghamton’s faculty in 2013.

Thanks to Project Lead The Way, an initiative that introduces students to STEM — science, technology, engineering and mathematics — subjects at an early age, Hays chose to research tissue engineering, the process of combining scaffolds, cells and biologically active molecules into functional tissues.

“It was science fiction come to life,” he says.

Now a senior biomedical engineering major at Binghamton University, Hays has a 4.0 average and a place working in the laboratory of Kaiming Ye, a professor and chair of the biomedical engineering department. “He’s a very smart and dedicated researcher,” Ye says. “He works hard, and he can solve a problem very quickly. His interests and his career goals are what made him stand out.”

Binghamton is one of the few universities working on 3D printing as a method of tissue engineering. Essentially, biocompatible material is “printed” in droplets that are then overlapped, eventually creating a bulky organ. This method allows for a lot more control over the “printing landscape,” Hays says.

Other schools, such as Harvard and Stony Brook University, are looking into a barrier in 3D printing known as the oxygen-diffusion limit, which says that a cell can’t survive outside of 100-200 microns from a vessel. “That’s like 1/10th of a millimeter,” Hays says. That’s why certain tissues, like skin and cartilage, lend themselves to the “printing” process more easily. They are relatively avascular, meaning they do not contain blood vessels.

Hays believes that in the next decade tissue engineering will make it possible to 3D print a fully functional organ created with a patient’s own cells or stem cells. For example, beta-islet cells — cells that produce, store and release the insulin hormone — are attacked and destroyed by the body’s immune system in Type 1 Diabetics. Tissue engineering may allow scientists to create beta-islet cells and produce a new artificial pancreas for these patients.

“Hopefully 3D printing will make something like the organ donor list obsolete in the near future,” Hays says.

In the meantime, Hays has found a way to save lives in the present day. He’s an emergency medical technician with the campus ambulance squad, Harpur’s Ferry. In the fall, he administered patient care and CPR that resuscitated someone in cardiac arrest.

“I was happy with how I responded,” Hays says. “It registered, but not emotionally. You realize you have a team. And if you learn how to work with your team, you’re never going to feel alone.”

Hays has been accepted into medical school for the fall, and he also looks forward to the possibility of using his engineering degree to become a biomedical consultant. He says he will always look at problems with an engineering mindset.

Hays and Rushi Shah, a fellow biomedical engineering student and Harpur’s Ferry EMT, realized there was not a device at the basic life support level to monitor respiratory heart rates automatically. They created an invention that they called a “respiratory quantifier,” which can measure and report respiratory rate in real time.

“I thought I would have to choose between biomedical engineering and medical school,” Hays says, “but in the end you don’t have to choose. You can do both.”