Brian Litt, professor in Engineering’s Department of Bioengineering and the Perelman School of Medicine’s departments of Neurology and Neurosurgery, has received a five-year, $5.6 million Pioneer Award from the National Institutes of Health, which will support his research on implantable devices for monitoring, recording and responding to neural activity.
The Pioneer Award is part of the agency’s High-Risk, High-Reward Research Program honoring exceptionally creative scientists. It challenges investigators to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science. Litt’s neurodevice research represents a new frontier in addressing a wide variety of neurological conditions.
In epilepsy, for example, these devices would predict and prevent seizures; in Parkinson’s patients, implants will measure and communicate with patients to improve mobility, reduce tremor and enhance responsiveness. Other implants might improve hearing or psychiatric symptoms by querying patient perceptions, feelings, and altering stimulation patterns algorithmically to improve them
Penn’s brainSTIM center will study neuromodulation to repair and enhance human brain function
Penn Medicine has launched a new center to study the brain, one of the most complex systems in the body:
The Penn Brain Science, Translation, Innovation, and Modulation (brainSTIM) Center brings together a team of leading neuroscientists, neurologists, psychiatrists, psychologists, and engineers at Penn using neuromodulation techniques to research, repair, and enhance human brain function—the first translational center of its kind in the region.
Among the key faculty involved in this new center is J. Peter Skirkanich Professor of Bioengineering Danielle Bassett. Bassett’s Complex Systems Lab studies biological, physical, and social systems by using and developing tools from network science and complex systems theory. Bassett, along with Assistant Professor of Psychiatry Desmond Oathes, will work to:
understand how TMS [i.e. transcranial magnetic stimulation] might improve working memory in healthy adults and those with ADHD by combining network control theory (a set of concepts and principles employed in engineering), magnetic stimulation of the brain, and functional brain imaging.
New 3D Tumor Models Could Improve Cancer Treatment
New ways of testing cancer treatments may now be possible thanks to researchers at the University of Akron who developed three-dimensional tumor models of triple-negative breast cancer. Led by Dr. Hossein Tavana, Ph. D., an associate professor of biomedical engineering at the university, the Tissue Engineering Microtechnologies Lab recently received a $1.13 million grant from the prestigious National Cancer Institute (NCI) of the National Institute of Health (NIH) to continue improving these tumor models. Tumors are difficult to fully replicate in vitro, as they are comprised of cancerous cells, connective tissue, and matrix proteins, among several other components. With this new grant, Tavana sees creating a high-throughput system that uses many identical copies of the tumor model for drug testing and better understanding of the way tumors operate. This high-throughput method would allow Tavana and his lab to isolate and test several different approaches at once, which they hope will help change the way tumors are studied and treated everywhere.
Noise-Induced Hearing Loss Poses Greater Threat to Neural Processing
Even though we all know we probably shouldn’t listen to music at high volumes, most of us typically do it anyway. But researchers at Purdue University recently found that noise-induced hearing loss could cause significant changes in neural processing of more complex sound inputs. Led by Kenneth Henry, Ph.D., an assistant professor of otolaryngology at the University of Rochester Medical Center, and Michael Heinz, Ph.D., a professor of biomedical engineering at Purdue University, the study shows that when compared with age-related hearing loss, noise-induced hearing loss will result in a greater decrease in hearing perception even when the two kinds of hearing loss appear to be of the same degree on an audiogram. This is because noise-induced hearing loss occurs because of physical trauma to the ear, rather than the long-term electrochemical degradation of some components that come happen with age. The evidence of this research is yet another reason why we should be more careful about exposing our ears to louder volumes, as they pose a greater risk of serious damage.
Increasing the Patient Populations for Research in Cartilage Therapy and Regenration
Despite the great progress in research of knee cartilage therapy and regeneration, there are still issues with the patient populations that most studies consider. Researchers often want to test new methods on patients that have the greatest chance of injury recovery without complications – often referred to as “green knees” – but this leaves out those patient populations who suffer from conditions or defects that have the potential to cause complications – often referred to as “red knees.” In a new paper published in Regenerative Medicine, the Mary Black Ralston Professor for Education and Research in Orthopaedic Surgery and secondary faculty in the Department of Bioengineering at Penn, Robert Mauck, Ph.D., discusses some cartilage therapies that may be suitable for red knee populations.
Working with James Carey, M.D., the Director of the Penn Center for Cartilage Repair and Osteochondritis, Mauck and his research team realized that even those with common knee cartilage conditions such as the presence of lesions or osteoarthritis were liable to be excluded from most regeneration studies. In discussing alternatives methods and structures of studying cartilage repair and regeneration, Mauck and Carey hope that future therapies will be applicable to a wider range of patient populations, and that there will soon be more options beyond full joint replacement for those with red knee conditions.
Plant-Like Superhydrophobicity Has Applications in Biomedical Engineering
Researchers in the Department of Biomedical Engineering at Texas A&M University recently found ways of incorporating the superhydrophobic properties of some plant leaves into biomedical applications through what they’re calling a “lotus effect.” The Gaharwar Lab, led by principal investigator and assistant professor of biomedical engineering Akhilesh Gaharwar, Ph.D., developed an assembly of two-dimensional atomic layers that they describe as a “nanoflower” to help control surface wetting in a biomedical setting. A recent paper published in Chemical Communications describes Gaharwar and his team’s work as expanding the use of superhydrophobic surface properties in biomedical devices by demonstrating the important role that atomic vacancies play in the wetting characteristic. While Gaharwar hopes to research the impact that controlling superhydrophobicity could have in stem cell applications, his work already allows for innovations in self-cleaning and surface properties of devices involving labs-on-a-chip and biosensing.
People and Places
Nader Engheta, H. Nedwill Ramsey Professor in Electrical and Systems Engineering, Bioengineering and Materials Science and Engineering, has been inducted into the Canadian Academy of Engineering (CAE) as an International Fellow. The CAE comprises many of Canada’s most accomplished engineers and Engheta was among the five international fellows that were inducted this year.
The Academy’s President Eddy Isaacs remarked: “Over our past 32 years, Fellows of Academy have provided insights in the fields of education, infrastructure, and innovation, and we are expecting the new Fellows to expand upon these contributions to public policy considerably.”
We would like to congratulate Anthony Lowman, Ph.D., on his appointment as the Provost and Senior Vice President for Academic Affairs at Rowan University. Formerly the Dean of Rowan’s College of Engineering, Lowman helped the college double in size, and helped foster a stronger research community. Lowman also helped to launch a Ph.D. program for the school, and added two new departments of Biomedical Engineering and Experiential Engineering Education in his tenure as the dean. Widely recognized for his research on hydrogels and drug delivery, Lowman was also formerly a professor of bioengineering at Temple University and Drexel University.
Lastly, we would like to congratulate Daniel Lemons, Ph.D., on his appointment as the Interim President of Lehman College of the City University of New York. Lemons, a professor in the Department of Biology at City College, specializes in cardiovascular and comparative physiology, and was also one of the original faculty members of the New York Center for Biomedical Engineering. With prior research funded by both the National Institute of Health (NIH) and the National Science Foundation (NSF), Lemons also holds patents in biomechanics teaching models and mechanical heart simulators.
These 12 object-number value pairs were taught to the participants, who had to properly learn the associations to succeed in value judgement tests. The researchers investigated the differences in their brain activity patterns to see why some were faster learners than others.
Why do some people naturally excel at learning instruments, languages or technology while others take longer to pick up new knowledge? Learning requires the brain to encode information, changing its neural “wiring” and creating networks between brain regions.
Earlier research has suggested that part of what might slow down learners is over-thinking. A 2015 study led by Danielle Bassett, Eduardo D. Glandt Faculty Fellow and associate professor in the Department of Bioengineering, showed a correlation between slow learning and cognitive control: the brain’s ability to regulate itself by activating the necessary networks and inhibiting unnecessary activity. In that study, when people unnecessarily engaged parts of the brain linked to cognitive control, they were more likely to take longer to learn a simple task.
But beyond what might make an individual learn more slowly, the researchers want to know what sort of geometric patterns of brain activity make for better learning.
Evelyn Tang and Danielle Bassett
Their new study was led by Bassett and Evelyn Tang, who was an Africk Family Postdoctoral Fellow in Bassett’s Complex Systems Lab before starting at the Max Planck Institute this fall. Sharon Thompson-Schill, Christopher H. Browne Distinguished Professor and chair of Psychology, also contributed to the study.
New Studies in Mechanobiology Could Open Doors for Cellular Disease Treatment
When we think of treatments at the cellular level, we most often think of biochemical applications. But what if we began to consider more biomechanical-oriented approaches in the regulation of cellular life and death? Under a grant from the National Science Foundation (NSF),Worcester Polytechnic Institute’s (WPI) Head of the Department of Biomedical Engineering Kristen Billiar, Ph.D., performs research that looks at the way mechanical stimuli can affect and trigger programmed cell death.
Billiar, who received his M.S.E. and Ph.D. from Penn, began his research by first noticing the way that cells typically respond to the mechanical stimuli in their everyday environment, such as pressure or stretching, with behaviors like migration, proliferation, or contraction. He and his research team hope to find a way to eventually predict and control cellular responses to their environment, which they hope could open doors to more forms of treatment for disorders like heart disease or cancer, where cellular behavior is directly linked to the cause of the disease.
Self-Learning Algorithm Could Help Improve Robotic Leg Functionality
Obviously, one of the biggest challenges in the field of prosthetics is the extreme difficulty in creating a device that perfectly mimics whatever the device replaces for its user. Particularly with more complex designs that involve user-controlled motion for joints in the limbs or hands, the electrical circuits implemented are by no means a perfect replacement of the neural connections in the human body from brain to muscle. But recently at the University of Southern California Viterbi School of Engineering, a team of researchers led by Francisco J. Valero-Cuevas, Ph. D., developed an algorithm with the ability to learn new walking tasks and adapt to others without any additional programming.
The algorithm will hopefully help to speed the progress of robotic interactions with the world, and thus allow for more adaptive technology in prosthetics, that responds to and learns with their users. The algorithm Valero-Cuevas and his team created takes inspiration from the cognition involved with babies and toddlers as they slowly learn how to walk, first through random free play and then from pulling on relevant prior experience. In a prosthetic leg, the algorithm could help the device adjust to its user’s habits and gait preferences, more closely mimicking the behavior of an actual human leg.
Neurofeedback Can Improve Behavioral Performance in High-Stress Situations
We’re all familiar with the concept of being “in the zone,” or the feeling of extraordinary focus that we can sometimes have in situations of high-stress. But how can we understand this shift in mindset on a neuroengineering level? Using the principal of the Yerkes-Dodson law, which says that there is a state of brain arousal that is optimal for behavioral performance, a team of biomedical engineering researchers at Columbia University hope to find ways of applying neurofeedback to improving this performance in demanding high-stress tasks.
Led by Paul Sajda, Ph.D., who received his doctoral degree from Penn, the researchers used a brain-computer interface to collect electroencephalography (EEG) signals from users immersed in virtual reality aerial navigation tasks of varying difficulty levels. In doing so, they were able to make connections between stressful situations and brain activity as transmitted through the EEG data, adding to the understanding of how the Yerkes-Dodson law actually operates in the human body and eventually demonstrating that the use of neurofeedback reduced the neural state of arousal in patients. The hope is that neurofeedback may be used in the future to help treat emotional conditions like post-traumatic stress disorder (PTSD).
Ultrasound Stimulation Could Lead to New Treatments for Inflammatory Arthritis
Arthritis, an autoimmune disease that causes painful inflammation in the joints, is one of the more common diseases among older patients, with more than 3 million diagnosed cases in the United States every year. Though extreme measures like joint replacement surgery are one solution, most patients simply treat the pain with nonsteroidal anti-inflammatory drugs or the adoption of gentle exercise routines like yoga. Recently however, researchers at the University of Minnesota led by Daniel Zachs, M.S.E., in the Sensory Optimization and Neural Implant Coding Lab used ultrasound stimulation treatment as a way to reduce arthritic pain in mice. In collaboration with Medtronic, Zachs and his team found that this noninvasive ultrasound stimulation greatly decreased joint swelling in mice who received the treatment as opposed to those that did not. They hope that in the future, similar methods of noninvasive treatment will be able to be used for arthritic patients, who otherwise have to rely on surgical remedies for serious pain.
People and Places
Leadership and Inspiration: EDAB’s Blueprint for Engineering Student Life
To undergraduates at a large university, the administration can seem like a mysterious, all-powerful entity, creating policy that affects their lives but doesn’t always take into account the reality of their day-to-day experience. The Engineering Deans’ Advisory Board (EDAB) was designed to bridge that gap and give students a platform to communicate with key decision makers.
The 13-member board meets once per week for 60 to 90 minutes. The executive board, comprised of four members, also meets weekly to plan out action items and brainstorm. Throughout his interactions with the group, board president Jonathan Chen, (ENG ‘19, W ‘19), has found a real kinship with his fellow board members, who he says work hard and enjoy one another’s company in equal measure.
Bioengineering major Daphne Cheung (ENG’19) joined the board as a first-year student because she saw an opportunity to develop professional skills outside of the classroom. “For me, it was about trying to build a different kind of aptitude in areas such as project management, and learning how to work with different kinds of people, including students and faculty, and of course, the deans,” she says.
Purdue University College of Engineering and Indiana University School of Medicine Team Up in New Engineering-Medicine Partnership
The Purdue University College of Engineering and the Indiana University School of Medicine recently announced a new Engineering-Medicine partnership, that seeks to formalize ongoing and future collaborations in research between the two schools. One highlight of the partnership is the establishment of a new M.D./M.S. degree program in biomedical engineering that will allow medical students at Indiana University to receive M.S.-level training in engineering technologies as they apply to clinical practice. The goal of this new level of collaboration is to further involve Purdue’s engineering program in the medical field, and to exhibit the benefits that developing an engineering mindset can have for medical students. The leadership of this new partnership includes
A new approach uses “mechanoceuticals” to treat pain.
Drugs are commonly injected directly into an injury site to speed healing. For chronic pain, clinicians can inject drugs to reduce inflammation in painful joints, or can inject nerve blockers to block the nerve signals that cause pain. In a recent study, a group from UCLA developed a technique to deform a material surrounding nerve fibers to trigger a response in the fibers that would relieve pain. The combination of mechanics and treatment – i.e., ‘mechanoceuticals’ – is a clever way to trick fibers and reverse painful symptoms. Done without any injections and simply controlling magnetic fields outside the body, this approach can be reused as necessary.
The design of this mechanoceutical was completed by Dino Di Carlo, PhD, Professor of Bioengineering, and his team at UCLA’s Sameuli School of Engineering. By encasing tiny, magnetic nanoparticles within a biocompatible hydrogel, the group used magnetic force to stimulate nerve fibers and cause a corresponding decrease in pain signals. This promising development opens up a new approach to pain management, one which can be created with different biomaterials to suit different conditions, and delivered “on demand” without worrying about injections or, for that matter, any prescription drugs.
Understanding the Adolescent Brain
It’s no surprise that adults and adolescents often struggle to understand one another, but the work of neurologists and other researchers provides a possible physical reason for why that might be. Magnetic resonance elastrography (MRE) is a tool used in biomedical imaging to estimate the mechanical properties, or stiffness, of tissue throughout the body. Unexpectedly, a recent study suggests that brain stiffness correlates with cognitive ability, suggesting MRE may provide insight into patients’ behavior, psychology, and psychiatric state.
A new paper in Developmental Cognitive Neuroscience published the results of a study using MRE to track the relative “stiffness” vs. “softness” of adult and adolescent brains. The University of Delaware team, led by Biomedical Engineering Assistant Professor Curtis Johnson, PhD, and his doctoral student Grace McIlvain, sampled 40 living subjects (aged 12-14) and compared the properties to healthy adult brains.
The study found that children and adolescent brains are softer than those of adults, correlating to the overall malleability of childhood development. The team hopes to continue their studies with younger and older children, looking to demonstrate exactly when and how the change from softness to stiffness takes place, and how these properties correspond to individual qualities such as risk-taking or the onset of puberty. Eventually, establishing a larger database of measurements in the pediatric brain will help further studies into neurological and cognitive disorders in children, helping to understand conditions such as multiple sclerosis, autism, and cerebral palsy.
Can Nanoparticles Replace Stents?
Researchers and clinicians have made amazing advances in heart surgery. Stents, in particular, have become quite sophisticated: they are used to both prop open clogged arteries as well as deliver blood-thinning medication slowly over days to weeks in the area of the stent. However, the risk of blood clotting increases with stents and the blood vessels can constrict over time after the stent is placed in the vessel.
A recent NIH grant will support the design of a stent-free solution to unclog blood vessels. Led by Shaoqin Gong, PhD, Vilas Distinguished Professor of Biomedical Engineering at UW-Madison, the team used nanoparticles (or nanoclusters) to directly target the affected blood vessels and prevent regrowth of the cells post-surgery, eliminating the need for a stent to keep the pathways open. These nanoclusters are injected through an intravenous line, further reducing the risks introduced by the presence of the stent. As heart disease affects millions of people worldwide, this new material has far-reaching consequences. Their study is published in the September edition of Biomaterials.
NIST Grant Supports
The National Institute of Standards and Technology (NIST) awarded a $30 million grant to Johns Hopkins University, Binghamton University, and Morgan State University as part of their Professional Research Experience Program (PREP). Over five years, this award will support the collaboration of academics from all levels (faculty, postdoc, graduate, and undergraduate) across the three universities, enabling them to conduct research and attend NIST conferences.
The principal investigator for Binghamton U. is Professor and Chair of the Biomedical Engineering Department, Kaiming Ye, PhD. Dr. Ye is also the Director of the Center of Biomanufacturing for Regenerative Medicine (CBRM), which will participate in this collaborative new enterprise. Dr. Ye hopes that this grant will create opportunities for academics and researchers to network with each other as well as to more precisely define the standards for the fields of regenerative medicine and biomaterial manufacturing.
The gift honors the late A. James Clark, former CEO of Clark Enterprises and Clark Construction Group LLC, one of the country’s largest privately-held general building contractors. It is designed to prepare future engineering and business leaders, with an emphasis on low income families and first-generation college students. Clark never forgot that his business successes began with an engineering scholarship. This has guided the Clark family’s longstanding investments in engineering education and reflects its commitment to ensure college remains accessible and affordable to high-potential students with financial need.
We are proud to say that three incoming Clark Scholars from the Freshman Class of 2022 will be part of the Bioengineering Department here at Penn.
And finally, our congratulations to the new Dean of the School of Engineering at the University of Mississippi: David A. Puleo, PhD. Dr. Puleo earned his bachelor’s degree and doctorate in Biomedical Engineering from Rensselaer Polytechnic Institute. Most recently he served as Professor of Biomedical Engineering and Associate Dean for Research and Graduate Studies at the University of Kentucky’s College of Engineering. Building on his research in regenerative biomaterials, he also founded Regenera Materials, LLC in 2014. Over the course of his career so far, Dr. Puleo received multiple teaching awards and oversaw much departmental growth within his previous institution, and looks poised to do the same for “Ole Miss.”
Seven-tesla MRI of the porcine mitral valve showing the papillary muscle (PM) and chordae tendinae (CT).
Since its invention in the early 1970s, magnetic resonance imaging (MRI) has played an increasingly important role in the diagnosis of illness. In addition, over time, the technology of MRI has evolved enormously, with the ability to render more detailed three-dimensional images using stronger magnetic fields . However, imaging tissues under mechanical loads (e.g., beating heart, lung breathing) are still difficult to image precisely with MRI.
A new study in PLOS One, led by Morten Jensen, Ph.D., of the University of Arkansas, breaks an important technical barrier in high resolution imaging for tissues under mechanical load. Using 3D-printed mounting hardware and 7-tesla MRI, this group produced some of the highest quality images yet produced of the mitral valve exposed to physiological pressures (see above). In the longer term, this method could point to new corrective surgical procedures that would greatly improve the repair procedures for mitral valves.
Oncology Breakthroughs
Among the most significant challenges faced by surgical oncologists is developing a ‘clear margin,’ meaning that the tissue remaining after tumor excision is free of any tumor cells. If the margins are not free of tumor cells, the cancer is more likely to recur. However, until now, it has been impossible to determine if cancer cells were still present in tissue margins before finishing surgery because of the time required to test specimens.
At the University of Texas, Austin, however, scientists are getting closer to overcoming this obstacle. In a recent study published in Science Translational Medicine, this team of scientists presents the MasSpecPen — short for mass spectrometry pen. This device is capable of injecting a tiny drop of water into tissue, extracting the water after it mixes with the tissue, and quickly analyzing the sample’s molecular components. The authors, who included biomedical engineering faculty member Thomas E. Milner, Ph.D., tested the device using ex vivo samples from 253 patients with different varieties of cancer, including breast, lung, and thyroid cancers. The MasSpecPen provided sensitivity, specificity, and accuracy exceeding 96% in all cases. Although it has yet to be tested intraoperatively, if effective under those conditions, the device could become an essential part of the surgeon’s arsenal.
If the MasSpecPen could render surgical treatment of cancer more effective, a device developed at SUNY Buffalo could help doctors diagnose lung cancer earlier. Lung cancer is a particularly deadly variety of cancer because patients don’t feel any discomfort until the cancer has spread to other areas of the body. In collaboration with Buffalo’s Roswell Park Center Institute, microchip manufacturer Intel, and local startup Garwood Medical Devices, a team of scientists, including Professor Edward P. Furlani, Ph.D., from Buffalo’s Department of Chemical and Biomedical Engineering, was awarded a grant from the National Science Foundation to develop a subcutaneous implant incorporating a nanoplasmonic biochip to detect biomarkers of lung cancer. A wearable smart band would receive data from the biochip and would act as an early warning system for lung cancer. The biomarkers selected for the biochip would optimally predict lung cancer risk much earlier than the metastasis stage. If the system that the team develops is successful in diagnosing lung cancer before it spreads, it could greatly improve survival and cure rates.
Feverish Growth
Worldwide but particularly in the Global South, malaria remains a major public health concern. According to a Global Burden of Disease study in 2015, there were nearly 300 million cases of the disease in a single year, with 731,000 fatalities. One of the earliest treatments to combat malaria was invented by British colonialists, who added quinine to the tonic used in the gin and tonic cocktail. More recently the drug artemisinin was developed for fighting malaria. However, this drug and its derivatives are very expensive. The primary reason for this cost is that the drug is extracted from the sweet wormwood plant, which is in short supply. In hopes of producing a greater supply of artemisinin, scientists collaborating among Denmark, Malaysia, and the Netherlands report in Frontiers in Bioengineering and Biotechnology that transplanting the genes responsible for producing atremisinin into Physcomitrella patens, a common moss, led to a much faster production rate of the drug than what is possible with the wormwood plant. The process proved simpler and less expensive than earlier attempts to transplant genes into tobacco plants. If this potential is harnessed correctly, it could make an enormous difference in lessening the global burden of malaria.
Understanding Fear
We’ve known for years about the flight-or-fight response — the adrenergic response of our bodies to danger, which we share in common with a number of other animals. Once the decision to flee is made, however, we know far less about what determines the escape strategy used. According to Malcolm A. MacIver, professor of biomedical engineering and mechanical engineering in Northwestern University’s McCormick School of Engineering, part of the escape strategy depends on how far away the attacker is. In a paper he coauthored that was published in Current Biology, Dr. MacIver studied threat responses in larval zebrafish and found that a fast-looming stimulus produced either freezing or escape at a shorter interval following the threat perception; when the perceived threat was slow looming, longer latency following the perception of the threat was seen, resulting in a greater variety of types of escape behaviors. While it might seem a giant leap between observing behaviors in fish and higher life forms, the basic mechanism in the “oldest” parts of the brain, from an evolutionary standpoint, are less different than we might think.
People and Places
The University of Maryland has announced that construction on a new building to serve as the home of its Department of Bioengineering will be finished by the end of September. The building is to be named A. James Clark Hall, after a builder, philanthropist, and alumnus of Maryland’s School of Engineering. Further south, George Mason University in Fairfax, Va., has announced that the new chair of its Department of Engineering there will be Michael Buschmann, Ph.D., an alumnus of MIT and faculty member since the 1990s at École Polytechnique in Montreal. Congratulations, Dr. Buschmann!
Penn’s brainSTIM center will study neuromodulation to repair and enhance human brain functio
New ways of testing cancer treatments may now be possible thanks to researchers at the University of Akron who developed three-dimensional tumor models of triple-negative breast cancer. Led by 
When we think of treatments at the cellular level, we most often think of biochemical applications. But what if we began to consider more biomechanical-oriented approaches in the regulation of cellular life and death? Under a grant from the National Science Foundation (NSF),Worcester Polytechnic Institute’s (WPI) Head of the Department of Biomedical Engineering 
