Syracuse University Magazine

Engineering Biomedical Advances

Engineering Biomedical Advances

Syracuse Biomaterials Institute researchers leverage collaboration and technology to create medical breakthroughs

By Julie Berry

Eric Ouellette ’10 completed a bachelor’s degree in biomedical engineering at the College of Engineering and Computer Science, and credits the serendipity of working in Syracuse Biomaterials Institute (SBI) founder Jeremy Gilbert’s laboratory with his decision to pursue a Ph.D. degree at SBI. He anticipates defense of his Ph.D. this spring and has interviewed with a health care company focused on orthopedic devices.

His work on polymers for use in hip and knee joint replacements is representative of the real-life impacts that come from cross-collaborations that SBI facilitates. SBI, located in Bowne Hall, is a haven where researchers, spurred by intellectual curiosity, work together to create medical breakthroughs that will potentially have impact during their lifetime.

In this collaborative institute, indeed often in the same building, SBI researchers Patrick Mather, James “Jay” Henderson, and Lisa Manning are working on projects that range from development of biodegradable smart tissues to enhance healing to development of computer models to predict effective treatment for such diseases as asthma and cancer. “What I like about biomedical engineering is the idea that you can influence the health care sector,” Ouellette says. “You’re not focused on one person at a time, but you can step back and make improvements in a lot of people’s lives. It has direct application. SBI has brought a lot of opportunities within research. There’s cross-talk and collaboration, with pooling of equipment, space, and resources. It’s a good opportunity to do interesting work with high-caliber faculty and teachers. In general, it’s a unique environment.”

According to Mather, who is the director of SBI and the Milton and Ann Stevenson Professor of Biomedical and Chemical Engineering, the institute’s culture promotes the pursuit of answers to problems that can’t be solved by individuals alone. Mather holds 14 patents. His research as a polymer scientist explores biodegradable elastomeric materials that can serve as blood vessel replacements, coronary stents, or even in the esophagus.

“Interdisciplinary fields stretch people. Projects have tangible goals,” Mather says. “Once we get a student into the laboratory, their skills take off.”

Plenty of students get the opportunity to have hands-on experiences, too. According to SBI, 35 faculty members worked with 150 students in 2014. From 2009 to 2014, the institute received about $13 million in external funding from federal, state, corporate, and foundation sources.



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As Eric Ouellette (top right) looks on, David Pierre prepares to apply a load to a femoral head/neck modular taper sample to engage and lock the two components, which are used in artificial hip joints, prior to corrosion testing. The two biomedical engineering doctoral students do research in Professor Jeremy Gilbert’s lab.

Photo by Steve Sartori



Joint Replacement
Ouellette’s work at SBI, under the direction of advisor Gilbert, focused on thermoplastic polymer use in metal hip replacement to reduce corrosion at the modular taper junction. Modular tapers are a design feature that allows the surgeon to assemble the implant ball and socket components during surgery to provide the best adaptation to and outcome for the patient. Corrosion may arise within the junction between these parts of the implant. Corrosion and wear in metal-on-metal hip joints is associated with inflammation, and designs that have metal-metal contacts have been a target of class-action lawsuits. “Corrosion is a big problem in hip and knee implants,” Ouellette says. “Clinical evidence indicates that corrosion is associated with a host of problems.”

To minimize corrosion at the modular taper junction, Gilbert and Ouellette developed polymer linings to improve the mechanical and electrochemical performance. The challenge is to develop a polymer that can withstand the tremendous amount of force applied on joints by regular body movements. “It’s like a thin gasket that electrically insulates,” Ouellette says.

An early recognition that foreign materials could be used in the body came during World War II when it was observed that fighter pilots suffered fewer eye infections from shards of windshields made of polymethyl methacrylate (PMMA), commonly known as Plexiglas, than glass. “Maybe the body doesn’t reject all materials,” says Gilbert, professor of biomaterials, Department of Biomedical and Chemical Engineering. “Now there is a lot of energy around materials for use in medicine. Students thrive on the thought of having an impact on their parent or grandparent.”

Inspiration can come from collaboration and influences outside of a narrow field of study. Gilbert cites Dr. Robert Jarvik ’68, H’83, inventor of the first successful artificial heart, who has said his advance was influenced most by metal working in a jewelry-making class. “You would think it would come from something in his field,” says Gilbert, who also has a strong focus in metals. “It’s bringing engineering to medicine.”

Gilbert is an engineer who began his career studying dental materials, including amalgam fillings, which is another use of foreign materials in the body, and he is now internationally recognized for his work in orthopedics. He is also a member on the Orthopaedic and Rehabilitation Panel of the Medical Devices Committee of the U.S. Food and Drug Administration.

The field of biochemistry is focused on how to control and manipulate cell mechanical and chemical factors. The future vision of regenerative medicine is how to turn off disease progression or regenerate tissue and asks how do you modify the body to get rid of arthritis or medical devices?

“I have spent a career [almost 35 years] studying metallic biomaterials, their surfaces, and their interactions with the biological system,” Gilbert says. “This has included working a lot with surgeons, scientists, and engineers and learning from them and thinking carefully about all that can go on at the surface of these implants. It’s been interesting, complicated, and fun.”

Since our bodies are essentially salt water, metal replacement joints have corroded. Clinical researchers initially thought the effects of corrosion on the body’s biological system were caused only by oxidation reactions that generate metal ions and metal oxide particles. “We have known for a long time in the biomaterials community that when metals corrode, it can have an effect on the local tissues,” Gilbert says. “Thus the focus has always been on the oxidation part of corrosion, and the role these ions and particles have on the tissues and cells nearby.”



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Professor Jeremy Gilbert, founder of the Syracuse Biomaterials Institute, confers in his lab with Eric Ouellette. 

Photo by Steve Sartori



Gilbert’s work shows that the biological effects of corrosion may also come from another type of reaction—a reduction reaction, which is thought to be produced during the interplay of oxygen and water with metal during corrosion reactions. During reduction reactions, byproducts, including hydrogen peroxide, hydroxide radicals, and others, are created. These byproducts can kill cells that are in contact with or near the metal surfaces. While this negative voltage reaction is not desired in medical implants, its impact as a potential to kill cancer cells or as an antibacterial agent is under investigation by Gilbert and chemical engineering professor Dacheng Ren, an SBI affiliate. “It’s such a complicated system,” Gilbert says. “A solution to one problem very frequently creates another problem.”

Gilbert has found that the body itself can also cause corrosion when compounds triggered by inflammation are released. When inflammation occurs, the cells involved generate and release reactive oxygen species, including chemicals like hydrogen peroxide and hypochlorous acid, that can increase the corrosion attack of alloys in the body. “It is also apparent that inflammation may accelerate corrosion by changing the fluid to be more aggressive in its attack of the metal,” Gilbert says. “So, for example, if significant inflammation occurs around an implant, the cells driving inflammation can release reactive oxygen species, which can cause a more severe attack of the metal surface. Therefore, corrosion can stimulate inflammation and inflammation can accelerate corrosion, creating a positive feedback between the two. This may result in both severe corrosion and severe inflammatory reactions in some patients.”

In the past, recipients of hip or knee implants were expected to adapt to their implants. Now as implants are more commonplace—with more than 500,000 hip implants and 1 million knee implants in the United States—demands are on making implants that fit the lifestyle of their users. Given the amount of use and sheer force on the metals, that’s a big challenge for manufacturers of biomedical devices. “The future is an interesting place,” Gilbert says. “The rate at which people get metal implants continues to grow exponentially. There’s a demand on the medical device industry. How do we manage this burgeoning need for these devices that have metal?”



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Professor James Henderson examines a temperature-sensitive biodegradable sleeve with doctoral students Shelby Buffington (left) and Megan Brasch. In the background are doctoral students Kyle Bishop and Michelle Pede. The sleeve is being developed to hold complex bone fractures in place and deliver bioactive agents to promote healing.

Photo by Steve Sartori



Smart Materials to Enhance Healing
Biomedical and chemical engineering professor James Henderson has been with SBI since its inception in 2007 and is focused on how to engineer tissue that can repair or replace damaged tissue, such as cartilage. “We are motivated by the opportunity to improve treatments for individuals with injuries, such as ACL tears, or diseases, such as arthritis or cancer,” he says.

Henderson observes how normal cells and tissues respond to their environment, and then develops smart materials that mimic this behavior. Smart materials are used to stabilize an injured site and to support natural tissue healing. Applications are for post-menopause osteopenia, which is a precursor to osteoporosis, a condition that decreases bone density and increases the risk of bone fractures; for controlling healing and scar tissue development; and for treatment of complex bone fractures.

In the example of bone fracture, if a tibia is shattered or crushed, multiple-stage surgeries are required and healing is poor because blood supply is low. “Bone is very good at healing, but some categories of fractures are hard to treat,” Henderson says. “Recovery is long and it impacts quality of life.” Even with surgery, bone may not heal, and the leg is sometimes amputated.

Henderson’s lab—in collaboration with the labs of SUNY Upstate orthopedics professor Megan Oest, who has expertise in bone fractures, and of SBI director Patrick Mather, who has expertise in shape memory polymers—has developed temperature-sensitive biodegradable sleeves that can hold bone in place and deliver bioactive agents, such as growth factors or antibiotics, to promote healing. “They’re like internal casts,” he says. These would replace metal hardware and eliminate multiple surgeries. And, because they’re temperature sensitive and have shape memory, they can be wrapped around the bone and 45-degree saline can be injected as a thermal signal for the sleeve to tighten during the surgical process. “Instead of a staged surgery, a patient could have a single surgery with no metal hardware,” says Henderson, noting human application is at least a decade off as research continues. “They’re back on their feet faster, with less loss of work time and less cost. One of the attractions for me with bioengineering is the ability to impact human society and quality of life with technology.”



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Cross-disciplinary collaboration is a key component of the institute’s work. One example is a mechanobiology project that SU professors James Henderson and Lisa Manning are working on with SUNY Upstate professor Christopher Turner (left).

Photo by Steve Sartori



Modeling Diseases
Henderson, Lisa Manning, a physics professor in the College of Arts and Sciences, and Christopher Turner, SUNY Upstate Distinguished Professor of Cell Development and Biology, are collaborating on a National Science Foundation grant-funded project that is focused on mechanobiology, an emerging field where biology and engineering overlap. Their project seeks to understand how and why cells move, and could have implications for cancer and congenital disease. Henderson’s research focuses on development of cell substrates, Turner provides molecular staining to track cell behavior, and Manning develops computer models to predict the behavior of large groups of cells. “We need to be willing to collaborate outside of our area of expertise,” Henderson says. “SBI is a unique research environment that brings different expertise under the same umbrella. It’s shared physical space, but also intellectual space. It provides a set of resources. Few places in the world have this level of integration.”

Henderson studies how cells naturally align and has successfully triggered changes in alignment. Knowing how and why cells move may lead to breakthroughs in metastasis of cancer cells. “We’re using shape-changing polymers to see if we can trigger cells to change shape and to better understand molecular interaction,” he says. “How this could matter? Cell motility and development are linked to and can lead to a better understanding of disease status, such as cancer.”

Manning takes a top-down, “bird’s-eye” view of cells, and observes their behavior as part of a group or tissue. She uses physics-based computational models to predict how cells move within large groups and how defects in cell motion cause disease. For example, her models predict that a small change in a single cell can generate a large change in tissue behavior and disease, a discovery that was recently published in Nature Physics. Manning and her group found that tiny alterations in a newly identified cell shape index can cause the entire tissue to transition from solid-like to fluid-like behavior. Having a small change make a large impact is a common concept in physics, but isn’t always applied to biology, Manning says.

Predicting the behavior of cells and tissue can have implications for the development of treatment for diseases such as asthma. Working with the Manning group, collaborators at the Harvard School of Public Health found that tissue from non-asthma patients quickly becomes solid-like, while tissue from asthma patients remains fluid-like longer. This work, which was published in Nature Materials, paves the way to test which treatments are most effective. “A delayed transition is a signature of asthma,” Manning says. “If we can identify what’s wrong, we can see if treatments can alter the transition.”

Asthma is one of many examples of these types of transitions. Manning has developed new collaborations to study their role in congenital disease and cancer, too. She has partnerships at SU, SUNY Upstate, Harvard School of Public Health, University of Chicago, and in Germany. “The combination of engineering and science,” she says, “is exciting, unique, and important.”  «

Photos by Steve Sartori



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“Once we get a student into the laboratory, their skills take off.” —PATRICK MATHER, (top right) director of Syracuse Biomaterials Institute 

Photo by Joe Librandi-Cowan



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