The NEMO Prize Goes to Research Improving Soft-Tissue Transplant Surgeries

by Melissa Pappas

Daeyeon Lee (left), Oren Friedman (center) and Sergei Vinogradov (right)

Each year, the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize, funded by Penn Health-Tech, awards $80,000 to a collaborative team of researchers from the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science for early-stage, interdisciplinary ideas.

This year, the NEMO Prize has been awarded to Penn Engineering’s Daeyeon Lee, Russel Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering, Oren Friedman, Associate Professor of Clinical Otorhinolaryngology in the Perelman School of Medicine, and Sergei Vinogradov, Professor in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Chemistry in the School of Arts & Sciences. Together, they are developing a new therapy that improves the survival and success of soft-tissue grafts used in reconstructive surgery.

More than one million people receive soft-tissue reconstructive surgery for reasons such as tissue trauma, cancer or birth defects. Autologous tissue transplants are those where cells and tissue such as fat, skin or cartilage are moved from one part of a patient’s body to another. As the tissue comes from the patient, there is little risk of transplant rejection. However, nearly one in four autologous transplants fail due to tissue hypoxia, or lack of oxygen. When transplants fail the only corrective option is more surgery. Many techniques have been proposed and even carried out to help oxygenate soft tissue before it is transplanted to avoid failures, but current solutions are time consuming and expensive. Some even have negative side effects. A new therapy to help oxygenate tissue quickly, safely and cost-effectively would not only increase successful outcomes of reconstructive surgery, but could be widely applied to other medical challenges. 

The therapy proposed by this year’s NEMO Prize recipients is a conglomerate or polymer of microparticles that can encapsulate oxygen and disperse it in sustainable and controlled doses to specific locations over periods of time up to 72 hours. This gradual release of oxygen into the tissue from the time it is transplanted to the time it functionally reconnects to the body’s vascular system is essential to keeping the tissue alive. 

“The microparticle design consists of an oxygenated core encapsulated in a polymer shell that enables the sustained release of oxygen from the particle,” says Lee. “The polymer composition and thickness can be controlled to optimize the release rate, making it adaptable to the needs of the hypoxic tissue.” 

These life-saving particles are designed to be integrated into the tissue before transplantation. However, because they exist on the microscale, they can also be applied as a topical cream or injected into tissue after transplantation. 

“Because the microparticles are applied directly into tissues topically or by interstitial injection (rather than being administered intravenously), they surpass the need for vascular channels to reach the hypoxic tissue,” says Friedman. “Their micron-scale size combined with their interstitial administration, minimizes the probability of diffusion away from the injury site or uptake into the circulatory system. The polymers we plan to use are FDA approved for sustained-release drug delivery, biocompatible and biodegrade within weeks in the body, presenting minimal risk of side effects.”

The research team is currently testing their technology in fat cells. Fat is an ideal first application because it is minimally invasive as an injectable filler, making it versatile in remodeling scars and healing injury sites. It is also the soft tissue type most prone to hypoxia during transplant surgeries, increasing the urgency for oxygenation therapy in this particular tissue type.

Read the full story in Penn Engineering Today.

Daeyeon Lee and Sergei Vinogradov are members of the Penn Bioengineering Graduate Group.

Arjun Raj Receives 2023-24 Heilmeier Award

by Olivia J. McMahon

Arjun Raj, Ph.D.

Arjun Raj, Professor in Bioengineering in Penn Engineering, has been named the recipient of the 2023-24 George H. Heilmeier Faculty Award for Excellence in Research for “pioneering the development and application of single-cell, cancer-fighting technologies.”

The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for the late George H. Heilmeier, a Penn Engineering alumnus and member of the School’s Board of Advisors, whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.

Raj, who also holds an appointment in Genetics in the Perelman School of Medicine, is a pioneer in the burgeoning field of single-cell engineering and biology. Powered by innovative techniques he has developed for molecular profiling of single cells, his scientific discoveries range from the molecular underpinnings of cellular variability to the behavior of single cells across biology, including in diseases such as cancer.

Raj will deliver the 2023-24 Heilmeier Lecture at Penn Engineering during the spring 2024 semester.

This story originally appeared in Penn Engineering Today.

Read more stories featuring Dr. Raj here.

Penn Bioengineers Awarded 2023 “Accelerating from Lab to Market Pre-Seed” Grants

Congratulations to the members of the Penn Bioengineering community who were awarded 2023 Accelerating from Lab to Market Pre-Seed Grants from the University of Pennsylvania Office of the Vice Provost for Research (OVPR).

Andrew Tsourkas, Ph.D.

Three faculty affiliated with Bioengineering were included among the four winners. Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), was awarded for his project titled “Precise labeling of protein scaffolds with fluorescent dyes for use in biomedical applications.” Tsourkas’s team created protein scaffold that can better control the location and orientation of fluorescent dyes, commonly used for a variety of biomedical applications, such as labeling antibodies or fluorescence-guided surgery. The Tsourkas Lab specializes in “creating novel targeted imaging and therapeutic agents for the detection and/or treatment of diverse diseases.”

Also awarded were Penn Bioengineering Graduate Group members Mark Anthony Sellmeyer, Assistant Professor in Radiology in the Perelman School of Medicine, and Rahul M. Kohli, Associate Professor of Medicine in the Division of Infectious Diseases in the Perelman School of Medicine.

From the OVPR website:

“Penn makes significant commitments to academic research as one of its core missions, including investment in faculty research programs. In some disciplines, the path by which discovery makes an impact on society is through commercialization. Pre-seed grants are often the limiting step for new ideas to cross the ‘valley of death’ between federal research funding and commercial success. Accelerating from Lab to Market Pre-Seed Grant program aims to help to bridge this gap.”

Read the full list of winning projects and abstracts at the OVPR website.

Paul Ducheyne Honored with 2023 ISCM Hironobu Oonishi Memorial Award

Paul Ducheyne, Ph.D.

Paul Ducheyne, Professor Emeritus in Bioengineering and Orthopaedic Surgery Research, has won the 2023 Hironobu Oonishi Memorial Award from the International Society for Ceramics in Medicine (ISCM). This award, the ISCM’s top honor, will only be awarded ten times in total, with previous honorees hailing from Japan and France and focusing on clinical research and life sciences. As the fifth honoree, Ducheyne is the first biomaterials researcher and engineer to win this distinguished prize.

Dr. Hironobu Oonishi was one of the founders of the International Society for Ceramics in Medicine and a leading hip surgeon. He was known for his discovery that irradiated polyethylene displayed greatly improved wear resistance in total joint replacements. In his memory, the ISCM and Kyocera created the Hironobu Oohnishi Memorial Award, with the goal to honor scientists who contributed to ISCM and greatly advanced the clinical use of bioceramics. Each year, the awardee is selected by a committee chaired by Dr. Hiroshi Oonishi, Dr. Hironobu Oonishi’s son. Once ten awardees have been selected, the award granting process will be closed.

Dr. Ducheyne accepted his award at the ISCM annual meeting in Solothurn, Switzerland in October 2023, where he delivered the Opening Ceremony lecture entitled “Bioceramics and Clinical Use – the struggle of memory against forgetting.”

Dr. Ducheyne has been a leading scientist in the field of biomaterial research for decades, with seminal contributions to biomaterials research, especially as it relates to orthopaedics. In bioceramics research, he clearly delineated the unusual properties of engineered bioactive ceramics. Not only was he at the vanguard of the development of these materials, he also generated a fundamental understanding of how these materials exhibit bone bioactive properties and promote skeletal healing. His group has also studied inorganic controlled release materials and has demonstrated the utility of sol-gel synthesized silica-based nanoporous materials for therapeutic use. These materials may well represent a next generation of agents for delivery of drugs, including antibiotics, analgesics, and osteogenic and anti-inflammatory molecules.

During his tenure at Penn, he directed the Center for Bioactive Materials and Tissue Engineering. He was also a Special Guest Professor at the KU Leuven, Belgium. He has founded several successful companies: XeroThera, a spin-out from Penn, that is developing advanced controlled delivery concepts for prophylaxis and treatment of surgical infections; Orthovita, a leading, independent biomaterials company in the world with more than 250 employees at the time of its acquisition by Stryker in June 2011; and Gentis, Inc., which focuses on breakthrough concepts for spinal disorders.

Congratulations to Dr. Ducheyne from everyone at Penn Bioengineering.

Combined Treatment Takes a Bite Out of Tooth Decay

by Nathi Magubane

Michel Koo of the School of Dental Medicine and David Cormode of the Perelman School of Medicine and the School of Engineering and Applied Science led a team of researchers that uncovered a way to combine two FDA-approved treatments to treat tooth decay that taps into the blend’s bacteria-killing capabilities without disrupting the mouth’s microbiome. (Image: iStock / Alex Sholom)

The sting of a toothache or the discovery of a cavity is a universal dread. Dental caries, more commonly known as tooth decay, is an insidious adversary, taking a toll on millions of mouths worldwide. Caries can lead to pain, tooth loss, infection, and, in severe cases, even death.

While fluoride-based treatments have long been the gold standard in dentistry, this singular approach is now dated and has limited effect. Current treatments do not sufficiently control biofilm—the main culprit behind dental caries—and prevent enamel demineralization at the same time. This dual dilemma becomes particularly pronounced in high-risk populations where the onset of the disease can be both rapid and severe.

Now, a study from a team of researchers led by Hyun (Michel) Koo of the University of Pennsylvania’s School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Science has unveiled an unexpected synergy in the battle against dental caries. Their research revealed that the combination of ferumoxytol (Fer) and stannous fluoride (SnF2) could point at a potent solution against dental caries. Their findings were published in Nature Communications.

“Traditional treatments often come short in managing the complex biofilm environment in the mouth,” Koo, senior co-author on the study, says. “Our combined treatment not only amplifies the effectiveness of each agent but does so with a lower dosage, hinting at a potentially revolutionary method for caries prevention in high-risk individuals.”

Read the full story in Penn Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and in the divisions of Pediatric Dentistry and Community Oral Health and the co-founder of the Center for Innovation & Precision Dentistry in the School of Dental Medicine at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

David Cormode is an associate professor of radiology and bioengineering with appointments in Penn’s Perelman School of Medicine and School of Engineering and Applied Science.

Other authors are Yue Huang, Nil Kanatha Pandey, Shrey Shah, and Jessica C. Hsu of Penn’s Perelman School of Medicine; Yuan Liu, Aurea Simon-Soro, Zhi Ren, Zhenting Xiaang, Dongyeop Kim, Tatsuro Ito, Min Jun Oh, and Yong Li of Penn’s School of Dental Medicine; Paul. J Smeets, Sarah Boyer, Xingchen Zhao, and Derk Joester of Northwestern University; and Domenick T. Zero of Indiana University.

The work was supported by the National Institute of Health (grants R01-DE025848 and TL1TR001423 and awards S10OD026871 and R90DE031532) and the National Science Foundation (awards ECCS-2025633 and DMR-1720139).

Leveraging the Body’s Postal System to Understand and Treat Disease

by Nathi Magubane

Microwell device with a solution in the reservoir (Image: Courtesy of David E. Reynolds)

Akin to the packages sent from one person to another via an elaborate postal system, cells send tiny parcels that bear contents and packaging material that serve key purposes: To protect the contents from the outside world and to make sure it gets to the right place via a label with an address. 

These packages are known as extracellular vesicles (EVs)—lipid-bound molecules that serve a variety of regulatory and maintenance functions throughout the body. They assist in the removal of unwanted materials within the cell, and they transport proteins, aid in DNA and RNA transfer, and promote tumorigeneses in cancerous cells. 

Given their myriad roles, EVs have taken center stage for many researchers in the biomedical space as they have the potential to improve current methods of disease detection and treatment. The main challenge, however, is accurately identifying the molecular contents of EVs while also characterizing the EVs, which, unlike other cellular components that are more homogenous, have more heterogeneity.

Now, a team of researchers at the University of Pennsylvania has developed a novel platform, droplet-free double digital assay, for not only profiling individual EVs but also accurately discerning their molecular contents. The researchers took the digital assay, which quantifies the contents of a molecule via binary metric—a 1 corresponds to the presence of a molecule and a zero to the lack thereof—and applies it to the EV. The work is published in Advanced Science.

The team was led by Jina Ko, an assistant professor with appointments in the School of Engineering and Applied Science and Perelman School of Medicine. “Our method allows for highly accurate quantification of the individual molecules inside an EV,” Ko says . “This opens up many doors in the realm of early disease detection and treatment.”

The researchers first compartmentalized individual EVs utilizing a microwell approach to isolate the EVs. Next, they captured individual molecules within the EVs and amplified the signal for clarity. The team then was able to determine the expression levels of pivotal EV biomarkers with remarkable precision via fluorescence.

Read the full story in Penn Today.

Jina Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and an assistant professor in the Department of Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania.

David Reynolds is a Ph.D. candidate in the Department of Bioengineering in Penn Engineering.

Other authors include, Menghan Pan, George Galanis, Yoon Ho Roh, Renee-Tyler T. Morales, Shailesh Senthil Kumar, and Su-Jin Heo of the Department of Bioengineering at Penn Engineering; Jingbo Yang and Xiaowei Xu of the Department of Pathology and Laboratory Medicine at Penn Medicine; and Wei Guo of the Department of Biology in the School of Arts & Sciences at Penn.

The research was supported by the National Institutes of Health: grants R00CA256353, R35 GM141832, and CA174523 (SPORE).

The Immune Health Future, Today

by Christina Hernandez Sherwood

Breaking the code of the immune system could provide a new fundamental way of understanding, treating, and preventing every type of disease. Penn Medicine is investing in key discoveries about immunity and immune system function, and building infrastructure, to make that bold idea a reality.

Several members of the Penn Bioengineering Graduate Group feature in this story which originally featured in the Penn Medicine Magazine.

Image: Courtesy of Penn Medicine Magazine

This grandfather lives with primary progressive multiple sclerosis (MS), an autoimmune disorder that he controls with a medicine that depletes his body of the type of immune cells that make antibodies. So while he has completed his COVID-19 vaccine course, his immune system function isn’t very strong—and the invitation has arrived at a time when COVID-19 is still spreading rapidly. 

You can imagine the scene as an older gentleman lifts a thick, creamy envelope from his mailbox, seeing his own name written in richly scripted lettering. He beams with pride and gratitude at the sight of his granddaughter’s wedding invitation. Yet his next thought is a sober and serious one. Would he be taking his life in his hands by attending the ceremony?

“In the past, all we could do was [measure] the antibody response,” says Amit Bar-Or, the Melissa and Paul Anderson President’s Distinguished Professor in Neurology at the Perelman School of Medicine, and chief of the Multiple Sclerosis division. “If that person didn’t have a good antibody response, which is likely because of the treatment they’re on, we’d shrug our shoulders and say, ‘Maybe you shouldn’t go because we don’t know if you’re protected.’” 

Today, though, Bar-Or can take a deeper dive into his patients’ individual immune systems to give them far more nuanced recommendations. A clinical test for immune cells produced in response to the COVID-19 vaccine or to the SARS-CoV-2 virus itself—not just antibodies—was one of the first applied clinical initiatives of a major new Immune Health® project at Penn Medicine. Doctors were able to order this test and receive actionable answers through the Penn Medicine electronic health record for patients like the grandfather with MS. 

“With a simple test and an algorithm we can have a very different discussion,” Bar-Or says. A test result showing low T cells, for instance, would tell Bar-Or his patient may get a meaningful jolt in immunity from a vaccine booster, while low antibody levels would suggest passive antibody therapy is more helpful. Or, the test might show his body is already well primed to protect him, making it reasonably safe to attend the wedding.

This COVID-19 immunity test is only the beginning. 

Physicians and scientists at Penn Medicine are imagining a future where patients can get a precise picture of their immune systems’ activity to guide treatment decisions. They are working to bring the idea of Immune Health to life as a new area of medicine. In labs, in complex data models, and in the clinic, they are beginning to make sense out of the depth and breadth of the immune system’s millions of as-yet-undeciphered signals to improve health and treat illnesses of all types. 

Penn Medicine registered the trademark for the term “Immune Health” in recognition of the potential impact of this research area and its likelihood to draw non-academic partners as collaborators in its growth. Today, at the south end of Penn’s medical campus, seven stories of research space are being added atop an office building at 3600 Civic Center Blvd., including three floors dedicated to Immune Health, autoimmunity, and immunology research.

The concept behind the whole project, says E. John Wherry, director of Penn Medicine’s Institute for Immunology and Immune Health (I3H), “is to listen to the immune system, to profile the immune system, and use those individual patient immune fingerprints to diagnose and treat diseases as diverse as immune-related diseases, cancer, cardiovascular disease, Alzheimer’s, and many others.”

The challenge is vast. Each person’s immune system is far more complex than antibodies and T cells alone. The immune system is made of multiple interwoven layers of complex defenders—from our skin and mucous membranes to microscopic memory B cells that never forget a childhood infection—meant to fortify our bodies from germs and disease. It is a sophisticated system that learns and adapts over our lifetimes in numerous ways, and it also falters and fails in some ways we understand and others that remain mysterious. And each person’s intricate internal battlefield is in some way unique.

The immune system is not just a set of defensive barricades, either. It’s also a potential source of deep insight about a person’s physiological functioning and responses to medical treatments.

“The immune system is sensing and keeping track of basically all tissues and all cells in our body all the time,” Wherry says. “It is surveying the body trying to clean up any invaders and restore homeostasis by maintaining good health.”

“Our goal is to essentially break the code of the immune system,” says Jonathan Epstein, executive vice dean of the Perelman School of Medicine and chief scientific officer at Penn Medicine. “By doing so, we believe we will be able to determine your state of health and your response to therapies in essentially every human disease.”

Read the full story in Penn Today.

Innovation and Impact: “RNA: Past, Present and Future”

by Melissa Pappas

(Left to right): Mike Mitchell, Noor Momin, and David Meaney recording the Innovation & Impact podcast.

In the most recent episode of the Penn Engineering podcast Innovation & Impact, titled “RNA: Past, Present and Future,” David F. Meaney, Senior Associate Dean of Penn Engineering and Solomon R. Pollack Professor in Bioengineering, is joined by Mike Mitchell, Associate Professor in Bioengineering, and Noor Momin, who will be joining Penn Engineering as an Assistant Professor in Bioengineering early next year, to discuss the impact that RNA has had on health care and biomedical engineering technologies.

Mitchell outlines his lab’s research that spans drug delivery, new technology in protecting RNA and its applications in treating cancer. Momin details her research, which is focused on optimizing the immune system to protect against illnesses such as cardiovascular diseases and cancer. With Meaney driving the discussion around larger questions, including the possibility of a cancer vaccine, the three discuss what they are excited about now and where the field is going in the future with these emerging, targeted treatments.

Read the full story in Penn Engineering Today.

Subscribe to the Innovation & Impact podcast on Apple Music, Spotify or your favorite listening platforms or find all the episodes on the Penn Engineering YouTube channel.

Two Penn Bioengineers Receive NIH Director Award

by Nathi Magubane

Jina Ko (left) and Kevin Johnson (right), both from the School of Engineering and the Perelman School of Medicine with appointments in Bioengineering, have received the National Institute of Health Director’s Award to support their “highly innovative and broadly impactful” research projects through the High-Risk, High-Reward program.

The National Institutes of Health (NIH) has awarded grants to three researchers from the University of Pennsylvania through the NIH Common Fund’s High-Risk, High-Reward Research program. The research of Kevin B. Johnson, Jina Ko, and Sheila Shanmugan will be supported through the program, which funds “highly innovative and broadly impactful” biomedical or behavioral research by exceptionally creative scientists.

The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting highly innovative research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to think “outside the box” and pursue trail-blazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.

Two Penn Bioengineering faculty, Johnson and Ko, are among 85 recipients for 2023.

Johnson, the David L. Cohen University Professor of Pediatrics, is a Penn Integrates Knowledge University Professor who holds appointments in the Department of Computer and Information Science in the School of Engineering and Applied Science and the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine. He also holds secondary appointments in Bioengineering, Pediatrics, and in the Annenberg School for Communication. He is widely known for his work with e-prescribing and computer-based documentation and, more recently, work communicating science to lay audiences, which includes a documentary about health-information exchange. Johnson has authored more than 150 publications and was elected to the American College of Medical Informatics, Academic Pediatric Society, National Academy of Medicine, International Association of Health Science Informatics, and American Institute for Medical and Biological Engineering.

Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and Department of Bioengineering in the School of Engineering and Applied Science. She focuses on developing single molecule detection from single extracellular vesicles and multiplexed molecular profiling to better diagnose diseases and monitor treatment efficacy. Ko earned her Ph.D. in bioengineering at Penn in 2018, during which time she developed machine learning-based microchip diagnostics that can detect blood-based biomarkers to diagnose pancreatic cancer and traumatic brain injury. For her postdoctoral training, she worked at the Massachusetts General Hospital and the Wyss Institute at Harvard University as a Schmidt Science Fellow and a NIH K99/R00 award recipient. Ko developed new methods to profile single cells and single extracellular vesicles with high throughput and multiplexing.

Read the full announcement in Penn Today.

Harnessing Artificial Intelligence for Real Biological Advances—Meet César de la Fuente

by Eric Horvath

In an era peppered by breathless discussions about artificial intelligence—pro and con—it makes sense to feel uncertain, or at least want to slow down and get a better grasp of where this is all headed. Trusting machines to do things typically reserved for humans is a little fantastical, historically reserved for science fiction rather than science. 

Not so much for César de la Fuente, PhD, the Presidential Assistant Professor in Psychiatry, Microbiology, Chemical and Biomolecular Engineering, and Bioengineering in Penn’s Perelman School of Medicine and School of Engineering and Applied Science. Driven by his transdisciplinary background, de la Fuente leads the Machine Biology Group at Penn: aimed at harnessing machines to drive biological and medical advances. 

A newly minted National Academy of Medicine Emerging Leaders in Health and Medicine (ELHM) Scholar, among earning a host of other awards and honors (over 60), de la Fuente can sound almost diplomatic when describing the intersection of humanity, machines and medicine where he has made his way—ensuring multiple functions work together in harmony. 

“Biology is complexity, right? You need chemistry, you need mathematics, physics and computer science, and principles and concepts from all these different areas, to try to begin to understand the complexity of biology,” he said. “That’s how I became a scientist.”

Read the full story in Penn Medicine News.