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.

Single-cell Cancer Detection Project Wins 2021 NEMO Prize

This scProteome-seq array shows separated protein biomarkers (green and magenta spots) from thousands of single cells.

Penn Health-Tech’s Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize awards $80,000 to support early-stage ideas joining engineering and medicine. The goal of the prize is to encourage collaboration between the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science by supporting innovative ideas that might not receive funding from traditional sources.

This year, the NEMO Prize has been awarded to a team of researchers from Penn Engineering’s Department of Bioengineering. Their project aims to develop a technology that can detect multiple cancer biomarkers in single cells from tumor biopsy samples.

As cancer cells grow in the body, one of the characteristics that influences tumor growth and response to treatment is cancer cell state heterogeneity, or differences in cell states. Methods that rapidly catalogue cell heterogeneity may be able to detect rare cells responsible for tumor growth and drug resistance.

Single-cell transcriptomics (scRNA-seq) is the standard method for studying cell states; by amplifying and analyzing the cell’s complement of RNA sequences at a given time, researchers can get a snapshot of what proteins the cell is in the process of making. However, this method does not fully capture the function of the cell. The field of proteomics, which captures the actual protein content of cells along with post-translational modifications, provides a better picture of the cell’s function, but single-cell proteomic methods with the same sensitivity as scRNA-seq do not currently exist.

Alex Hughes, Lukasz Bugaj and Andrew Tsourkas

This collaborative project, which joins Assistant Professors Alex Hughes and Lukasz Bugaj, as well as Professor Andrew Tsourkas, aims to change that by developing multiplexed, sensitive and highly specific single-cell proteomics technologies to advance our understanding of cancer, its detection and its treatment.

This new technology, called scProteome-seq, builds from Hughes’s previous work.

“My specific expertise here is as an inventor of single-cell western blotting, which is the core technology that our team is building on,” says Hughes. “Single-cell proteomics technologies of this type have a track-record of commercial translation for applications in basic science and clinical automation, so our approach has a high potential for real-world impact.”

The current technology from Hughes’ lab separates proteins in cells by their molecular weight and “blots” them on a piece of paper. Improvements to this technology included in this project will remove the limitation of using light-emitting dyes to detect different proteins and instead use DNA barcodes to differentiate them.

Read the full story in Penn Engineering Today.

Penn Health-Tech Q&A with César de la Fuente

Created in the lab of César de la Fuente, this miniaturized, portable version of rapid COVID-19 test, which is compatible with smart devices, can detect SARS-CoV-2 within four minutes with nearly 100% accuracy. (Image: Courtesy of César de la Fuente)

César de la Fuente, Presidential Assistant Professor in Bioengineering, Chemical and Biomolecular Engineering, Microbiology, and Psychiatry, was the inaugural recipient of the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize from Penn Health-Tech in 2020 for his low-cost, rapid COVID test. Now with promising results recently published in the journal Matter (showing 90 percent accuracy in as little as four minutes), Penn Health-Tech caught up with de la Fuente to discuss his experience over the past year:

“How did [your project] evolve in the past year?

‘We started with one prototype and now have three entirely different prototypes for the test. Two use electrochemistry, and we are now working on a new technology that uses calorimetry. With calorimetry, when the cotton swabs are exposed to the virus, they change color. This means users are able to see if they’re affected by a virus through a simple color change, making it more of a visual detection method.'”

Read the full Q&A in the Penn Health-Tech blog.

César de la Fuente Wins Inaugural NEMO Prize, Will Develop Rapid COVID Virus Breath Tests

The paper-based tests could be integrated directly into facemasks and provide instant results at testing sites.

Cesar de la Fuente-Nunez, PhD

When Penn Health-Tech announced its Nemirovsky Engineering and Medicine Opportunity, or NEMO Prize, in February, the center’s researchers could only begin to imagine the impact the looming COVID-19 pandemic was about to unleash. But with the promise of $80,000 to support early-stage ideas at the intersection of engineering and medicine, the contest quickly sparked a winning innovation aimed at combating the crisis.

Judges from the University of Pennsylvania’s School of Engineering and Applied Sciences and Perelman School of Medicine awarded its first NEMO Prize to César de la Fuente, PhD, who proposed a paper-based COVID diagnostic system that could capture viral particles on a person’s breath, then give a result in a matter of seconds when taken to a testing site.

Similar tests for bacteria cost less than a dollar each to make. De la Fuente, a Presidential Assistant Professor in the departments of Psychiatry, Microbiology, and Bioengineering, is aiming to make COVID tests at a similar price point and with a smaller footprint so that they could be directly integrated into facemasks, providing further incentive for their regular use.

“Wearing a facemask is vital to containing the spread of COVID because, before you know you’re sick, they block your virus-carrying droplets so those droplets can’t infect others,” de la Fuente says. “What we’re proposing could eventually lead to a mask that can be infected by the virus and let you know that you’re infected, too.”

De la Fuente’s lab has conducted molecular dynamic simulations of the regions of the SARS-COV-2 spike protein (blue) that bind to the human ACE2 receptor (red and yellow).

De la Fuente’s expertise is in synthetic biology and molecular-scale simulations of disease-causing viruses and bacteria. Having such fine-grained computational models of these microbes’ binding sites allow de la Fuente to test them against massive libraries of proteins, seeing which bind best. Other machine learning techniques can then further narrow down the minimum molecular structures responsible for binding, resulting in functional protein fragments that are easier to synthesize and manipulate.

The spike-shaped proteins that give coronaviruses their crown-like appearance and name bind to a human receptor known as ACE2. De la Fuente and his colleagues are now aiming to characterize the molecular elements and environmental factors that would allow for the most precise, reliable detection of the virus.

Read the full story on the Penn Engineering blog.