Little Bots That Could Put a Stop to Infectious Disease

Image: Courtesy of iStock / K_E_N

Biofilms—structured communities of microorganisms that create a protective matrix shielding them from external threats, including antibiotics—are responsible for about 80% of human infections and present a significant challenge in medical treatments, often resisting conventional methods.

In a Q&A with Penn Today, Hyun (Michel) Koo of the School of Dental Medicine and Edward Steager of the School of Engineering and Applied Science at Penn discuss an innovative approach they’ve partnered on: the use of small-scale robotics, microrobots, to offer a promising solution to tackle these persistent infections, bringing new capabilities and precision to the field of biomedical engineering.

Q: What is the motivation behind opting for tiny robots to tackle infections?

Koo: Treating biofilms is a broad yet unresolved biomedical problem, and conversely, the strategies for tackling biofilms are limited for a number of reasons. For instance, biofilms typically occur on surfaces that can be tricky to reach, like between the teeth in the oral cavity, the respiratory tract, or even within catheters and implants, so treatments for these are usually restricted to antibiotics (or antimicrobials) and other physical methods reliant on mechanical disruption. However, this touches on the problem of antimicrobial resistance: targeting specific microorganisms present in these structures is difficult, so antibiotics often fail to reach and penetrate the biofilm’s protective layers, leading to persistent infections and increased risk of antibiotic resistance.

We needed a way to circumvent these constraints, so Ed and I teamed up in 2017 to develop new, more precise and effective approaches that leverage the engineers’ ability to generate solutions that we, the clinicians and life science researchers, identify.

Read the full interview 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.

Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.

Penn Bioengineering Student Kaitlin Mrksich Wins Outstanding Research Award from the Society for Biomaterials

Kaitlin Mrksich, an undergraduate student in Penn Bioengineering, was honored with the Student Award for Outstanding Research (Undergraduate) by the Society for Biomaterials (SFB). This prestigious award recognizes undergraduate students who have shown outstanding achievement in biomaterials research.

Mrksich is a third-year student from Hinsdale, Illinois. She is interested in developing drug delivery systems that can serve as novel therapeutics for a variety of diseases. She works in the lab of Michael Mitchell, Associate Professor in Bioengineering. In the Mitchell Lab, Mrksich investigates the ionizable lipid component of lipid nanoparticles for mRNA delivery.

“In Kaitlin’s independent projects, she has focused on probing the role of lipophilicity and chirality for LNP-mediated mRNA delivery,” Mitchell said in the award announcement. “She has synthesized dozens of unique lipids, formulated these lipids into LNPs, and evaluated their potential for mRNA delivery in vivo and in primary T cells. She has been able to deduce structure-function relationships that help explain the role of lipid hydrophobicity in the delivery of mRNA by LNPs. Her findings have not only been instrumental in helping our lab design better LNPs but will also provide fundamental knowledge that will benefit all labs working on LNP technology.”

In addition to her academic activities, Mrksich is also the President of the Penn Biomedical Engineering Society (BMES), where she plans community-building and professional-development events for bioengineering majors, and the visit coordinator for special programs for the Kite and Key Society, where she organizes virtual programming to introduce prospective students to Penn. She also tutors a West Philadelphia high school student in chemistry as part of the West Philadelphia Tutoring Project and is a member of Tau Beta Pi engineering honor society and Sigma Kappa sorority. After graduating, she plans to pursue an M.D.-Ph.D. in Bioengineering. 

Read the full list of 2024 SFB award recipients here.

Riccardo Gottardi Receives BMES Rising Star Award

Riccardo Gottardi, Ph.D.

Riccardo Gottardi, Assistant Professor in Pediatrics and in Bioengineering and leader of the Bioengineering and Biomaterials Laboratory at the Children’s Hospital of Philadelphia (CHOP), received the Rising Star Award from the Biomedical Engineering Society-Cellular and Molecular Bioengineering (BMES-CMBE). The Rising Star Award recognizes a BMES-CMBE member who is at the early independent career stage and has made an outstanding impact on the field of cellular and molecular bioengineering. Awardees will give an oral presentation on their research at the BMES-CMBE conference in Puerto Rico in January and be recognized at the conference Gala dinner.

Dr. Gottardi’s research focuses on engineering solutions for pediatric health, primarily for airway disorders. He has previously received awards for work to create a biomaterial patch to repair the tympanic membrane and for work to develop cartilage implants to treat severe subglottic stenosis. He received grant support from the National Institutes of Health to further his work in subglottic stenosis.

This story originally appeared in the CHOP Cornerstone Blog.

Sydney Shaffer Wins Christopher J. Marshall Award for Melanoma Research

Sydney Shaffer, M.D., Ph.D.

Sydney Shaffer, Assistant Professor in Bioengineering in the School of Engineering and Applied Science and in Pathology and Laboratory Medicine in the Perelman School of Medicine, was named the 2023 Christopher J. Marshall Award winner by the Society for Melanoma Research (SMR). The award recognizes Shaffer’s contributions to melanoma research on oncogenic signalling and molecular pathogenesis of this disease, as well as her rapid development as a rising star and leader in the field, which have helped to further the SMR’s goal to eradicate melanoma. The award was presented at the SMR annual meeting in Philadelphia in November 2023. 

The Christopher J. Marshall Award was established in 2015 by the SMR in partnership with Melanoma Research Foundation Congress to recognize a student, postdoctoral fellow, or new independent PI who has published a substantial and original contribution to studies of signal transduction and melanoma.

Shaffer joined Penn as an Assistant Professor in 2019. She holds a M.D.-Ph.D. in Medicine and Bioengineering from the University of Pennsylvania and conducted postdoctoral research in cancer biology in the lab of Junwei Shi, Associate Professor in Penn Medicine. The Syd Shaffer Lab is an interdisciplinary team which focuses on “understanding how differences between single-cells generate phenotypes such as drug resistance, oncogenesis, differentiation, and invasion [using] a combination of imaging and sequencing technologies to investigate rare single-cell phenomena.” A recent paper in Nature Communications details the team’s method to quantify long-lived fluctuations in gene expression that are predictive of later resistance to targeted therapy for melanoma.

Read the award announcement and the full list of prior winners at the SMR website.

Penn Scientists Reflect on One Year of ChatGPT

by Erica Moser

René Vidal, at the podium, introduces the event “ChatGPT turns one: How is generative AI reshaping science?” Bhuvnesh Jain, left at the table, moderated the discussion with Sudeep Bhatia, Konrad Kording, Andrew Zahrt, and Nick Pangakis.

As a neuroscientist surveying the landscape of generative AI—artificial intelligence capable of generating text, images, or other media—Konrad Kording cites two potential directions forward: One is the “weird future” of political use and manipulation, and the other is the “power tool direction,” where people use ChatGPT to get information as they would use a drill to build furniture.

“I’m not sure which of those two directions we’re going but I think a lot of the AI people are working to move us into the power tool direction,” says Kording, a Penn Integrates Knowledge (PIK) University professor with appointments in the Perelman School of Medicine and School of Engineering and Applied Science. Reflecting on how generative AI is shifting the paradigm of science as a discipline, Kording said he thinks “it will push science as a whole into a much more collaborative direction,” though he has concerns about ChatGPT’s blind spots.

Kording joined three University of Pennsylvania researchers from the chemistry, political science, and psychology departments sharing their perspectives in the recent panel “ChatGPT turns one: How is generative AI reshaping science?” PIK Professor René Vidal opened the event, which was hosted by the School of Arts & Sciences’ Data Driven Discovery Initiative (DDDI), and Bhuvnesh Jain, physics and astronomy professor and co-faculty director of DDDI, moderated the discussion.

“Generative AI is moving so rapidly that even if it’s a snapshot, it will be very interesting for all of us to get that snapshot from these wonderful experts,” Jain said. OpenAI launched ChatGPT, a large language model (LLM)-based chatbot, on Nov. 30, 2022, and it rapidly ascended to ubiquity in news reports, faculty discussions, and research papers. Colin Twomey, interim executive director of DDDI, told Penn Today that it’s an open question as to how it will change the landscape of scientific research, and the` idea of the event was to solicit colleagues’ opinions on interesting directions in their fields.

Read the full story in Penn Today.

Konrad Paul Kording is Nathan Francis Mossell University Professor in Bioengineering and Computer and Information Science in Penn Engineering and in Neuroscience in the Perelman School of Medicine.

Herman P. Schwan Distinguished Lecture: “Seeing the Unseen: How AI Redefines Bioengineering” (Dorin Comaniciu, Siemens Healthineers)

Dorin Comaniciu, Ph.D.

We hope you will join us for the 2023 Herman P. Schwan Distinguished Lecture by Dr. Dorin Comaniciu, hosted by the Department of Bioengineering.

Wednesday, December 13, 2023
1:00 PM ET
Location: Wu & Chen Auditorium (Levine 101)
The lecture and Q&A will be followed by a light reception in Levine Lobby.

Speaker: Dorin Comaniciu, Ph.D.
Senior Vice President
Artificial Intelligence and Digital Innovations
Siemens Healthineers

About Dorin Comaniciu:

Dr. Comaniciu serves as Senior Vice President for Artificial Intelligence and Digital Innovation at Siemens Healthineers. His scientific contributions to machine intelligence and computational imaging have translated to multiple clinical products focused on improving the quality of care, specifically in the fields of diagnostic imaging, image-guided therapy, and precision medicine.

Comaniciu is a member of the National Academy of Medicine, the Romanian Academy, and a Top Innovator of Siemens. He is a Fellow of the IEEE, ACM, MICCAI Society, and AIMBE, and a recipient of the IEEE Longuet-Higgins Prize for fundamental contributions to computer vision. Recent recognition of his work includes an honorary doctorate from Friedrich-Alexander University of Erlangen-Nuremberg.

He has co-authored 550 granted patents and 350 peer-reviewed publications that have received 61,000 citations, with an h-index of 102, in the areas of machine intelligence, medical imaging, and precision medicine.

A graduate of University of Pennsylvania’s Wharton School, Comaniciu received a doctorate in electrical and computer engineering from Rutgers University and a doctorate in electronics and telecommunications from Polytechnic University of Bucharest.

He is an advocate for technological innovations that save and enhance lives, addressing critical issues in global health.

About the Schwan Lecture:

The Herman P. Schwan Distinguished Lecture is in honor of one of the founding members of the Department of Bioengineering, who emigrated from Germany after World War II and helped create the field of bioengineering in the US. It recognizes people with a similar transformative impact on the field of bioengineering.

How Penn Medicine Is Changing the World with mRNA

by Rachel Ewing

Vaccines for COVID-19 were the first time that mRNA technology was used to address a worldwide health challenge. The Penn Medicine scientists behind that technology were awarded the 2023 Nobel Prize in Physiology or Medicine. Next come all the rest of the potential new treatments made possible by their discoveries.

Starting in the late 1990s, working together at Penn Medicine, Katalin Karikó, PhD, and Drew Weissman, MD, PhD, discovered how to safely use messenger RNA (mRNA) as a whole new type of vaccine or therapy for diseases. When the COVID-19 pandemic hit in 2020, these discoveries made Pfizer/BioNTech and Moderna’s new vaccines possible—saving millions of lives. 

But curbing the pandemic was only the beginning of the potential for this Nobel Prize-winning technology. 

These biomedical innovations from Penn Medicine in using mRNA represent a multi-use tool, not just a treatment for a single disease. The technology’s potential is virtually unlimited; if researchers know the sequence of a particular protein they want to create or replace, it should be possible to target a specific disease. Through the Penn Institute for RNA Innovation led by Weissman, who is the Roberts Family Professor of Vaccine Research in Penn’s Perelman School of Medicine, researchers are working to ensure this limitless potential meets the world’s most challenging and important needs.

Infectious Diseases and Beyond

Just consider some of the many projects Weissman’s lab is partnering in: “We’re working on malaria with people across the U.S. and in Africa,” Weissman said. “We’re working on leptospirosis with people in Southeast Asia. We’re working on vaccines for peanut allergies. We’re working on vaccines for autoimmunity. And all of this is through collaboration.”

Clinical trials are underway for the new malaria vaccine, as well as for a Penn-developed mRNA vaccine for genital herpes and one that aims to protect against all varieties of coronaviruses. Trials should begin soon for vaccines for norovirus and the bacterium C. difficile.

Single-Injection Gene Therapies for Sickle Cell and Heart Disease

Drew Weissman, MD, PhD, is a co-winner of the 2023 Nobel Prize in Physiology or Medicine for discoveries with mRNA.

The Weissman lab is working to deploy mRNA technology as an accessible gene therapy for sickle cell anemia, a devastating and painful genetic disease that affects about 20 million people around the world. About 300,000 babies are born each year with the condition, mainly in sub-Saharan Africa. Weissman’s team has developed technology to efficiently deliver modified mRNA to bone marrow stem cells, instructing red blood cells to produce normal hemoglobin instead of the malformed “sickle” version that causes the illness. Conventional gene therapies are complex and expensive treatments, but the mRNA gene therapy could be a simple, one-time intravenous injection to cure the disease. Such a treatment would have applications to many other congenital gene defects in blood and stem cells.

In another new program, Penn Medicine researchers have found a way to target the muscle cells of the heart. This gene therapy method developed by Weissman’s team, together with Vlad Muzykantov, MD, PhD, the Founders Professor in Nanoparticle Research could potentially repair the heart or increase blood flow to the heart, noninvasively, after a heart attack or to correct a genetic deficiency in the heart. “That is important because heart disease is the number one killer in the U.S. and in the world,” Weissman said. “Drugs for heart disease aren’t specific for the heart. And when you’re trying to treat a myocardial infarction or cardiomyopathy or other genetic deficiencies in the heart, it’s very difficult, because you can’t deliver to the heart.”

Weissman’s team also is partnering on programs for neurodevelopmental diseases and for neurodegenerative diseases, to replace genes or deliver therapeutic proteins that will treat and potentially cure these diseases.

“The potential is unbelievable,” Weissman said. “We haven’t thought of everything that can be done.”

Read the full story in Penn Medicine News.

Vladimir R. Muzykantov is Founders Professor in Nanoparticle Research in the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.

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 Partners in Multi-University Research Center Supporting Healthy Pregnancies

by Andrew Smith

How does the placenta keep harmful substances away from developing babies while still providing proper nutrition?

(Photo: Getty Images)

The exact mechanisms remain unknown, which is why the University of Pennsylvania, Rutgers University, Tulane University, the University of North Carolina at Chapel Hill and the University of Rochester have joined together to launch a research center dedicated to solving this mystery and ensuring healthy pregnancies.

A $5 million grant from the National Institutes of Health (NIH) will help fund the Integrated Transporter Elucidation Center (InTEC), which will operate from the Rutgers Biomedical Health Sciences campus in Piscataway under the leadership of Lauren Aleksunes, a professor of pharmacology and toxicology at Rutgers’ Ernest Mario School of Pharmacy and resident scientist in the Environmental and Occupational Health Sciences Institute (EOHSI).

“Since my time working as a community pharmacist, I have found the lack of high-quality information about the safety of everyday products on the health of a pregnancy frustrating,” says Aleksunes.  “People need to know whether the chemicals in their diet, personal care products and medications can impact their babies. Our goal at InTEC is to better understand how these chemicals travel in and out of the placenta and if they can reach the baby and influence their development.”

Aleksunes will study how transporter proteins carrying nutrients, dietary supplements, medications and toxic chemicals work during pregnancies. Some of the work will test how individual placenta cells respond to various stimuli in the laboratory. Others on the team will examine how environmental factors influence placental transporters during healthy and unhealthy or complicated pregnancies. 

Key to this work will be Dan Huh, Associate Professor in Bioengineering in Penn Engineering, who will lead a team with an innovative approach to modeling the transfer of molecules across the human placenta. 

As a pioneer of organ-on-a-chip technology, the Huh group will use a novel microengineered system in which maternal tissue engineered from a layer of primary human trophoblasts is grown adjacent to a three-dimensional network of perfusable fetal blood vessels to mimic the human placental barrier. This microphysiological system will be employed as an in vitro platform to simulate and quantitatively analyze the exchange of various substances between maternal and fetal circulation without the need for laboratory animals or placenta explants.

Read the full story in Penn Engineering Today.