Penn Bioengineering Alumna Cynthia Reinhart-King is President Elect of BMES

Dr. Cynthia Reinhart-King, Engineering, BME, Photo by Joe Howell

Penn Bioengineering alumna Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering and Professor of Biomedical Engineering at Vanderbilt University, was elected the next President of the Biomedical Engineering Society (BMES), the largest professional society for biomedical engineers. Her term as president-elect started at the annual BMES meeting in October 2021.

Reinhart-King graduated with her Ph.D. from Penn Bioengineering in 2006. She studied in the lab of Daniel Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and Chemical and Biomolecular Engineering as a Whitaker Fellow and went on to complete postdoctoral training as an Individual NIH NRSA postdoctoral fellow at the University of Rochester. Prior to joining Vanderbilt, she was on the faculty of Cornell University and received tenure in the Department of Biomedical Engineering. The Reinhart-King lab at Vanderbilt “uses tissue engineering, microfabrication, novel biomaterials, model organisms, and tools from cell and molecular biology to study the effects of mechanical and chemical changes in tissues during disease progression.”

Reinhart-King gave the 2019 Grace Hopper Distinguished Lecture, sponsored by the Department of Bioengineering. This lecture series recognizes successful women in engineering and seeks to inspire students to achieve at the highest level. She is a recipient of numerous prestigious awards, including the Rita Schaffer Young Investigator Award in 2010, an NSF CAREER Award, and the Mid-Career Award in 2018 from BMES.

In a Q&A on the BMES Blog, Reinhart-King said that:

“BMES is facing many challenges, like many societies, as we deal with the hurdles associated with COVID-19 and inequities across society. We must continue to address those challenges. However, we are also in a terrific window of having robust membership, many members who are eager to get involved with the society’s activities, and a national lens on science and scientists. One of my goals will be to identify and create opportunities for our members to help build the reach of the society and its member.”

Read “Cynthia Reinhart-King is president-elect of the Biomedical Engineering Society” in Vanderbilt News.

Penn Engineering’s Latest ‘Organ-On-a-Chip’ is a New Way to Study Cancer-related Muscle Wasting

by Melissa Pappas

Bioengineering’s Dan Huh and colleagues have developed a number of organ-on-a-chip devices to simulate how human cells grow and perform in their natural environments. Their latest is a muscle-on-a-chip, which carefully captures the directionality of muscle cells as they anchor themselves within the body. See the full infographic at the bottom of this story. (Illustration by Melissa Pappas).

Studying drug effects on human muscles just got easier thanks to a new “muscle-on-a-chip,” developed by a team of researchers from Penn’s School of Engineering and Applied Science and Inha University in Incheon, Korea.

Muscle tissue is essential to almost all of the body’s organs, however, diseases such as cancer and diabetes can cause muscle tissue degradation or “wasting,” severely decreasing organ function and quality of life. Traditional drug testing for treatment and prevention of muscle wasting is limited through animal studies, which do not capture the complexity of the human physiology, and human clinical trials, which are too time consuming to help current patients.

An “organ-on-a-chip” approach can solve these problems. By growing real human cells within microfabricated devices, an organ-on-a-chip provides a way for scientists to study replicas of human organs outside of the body.

Using their new muscle-on-a-chip, the researchers can safely run muscle injury experiments on human tissue, test targeted cancer drugs and supplements, and determine the best preventative treatment for muscle wasting.

organ-on-a-chip
Dan Huh, Ph.D.

This research was published in Science Advances and was led by Dan Huh, Associate Professor in the Department of Bioengineering, and Mark Mondrinos, then a postdoctoral researcher in Huh’s lab and currently an Assistant Professor of Biomedical Engineering at Tulane University. Their co-authors included Cassidy Blundell and Jeongyun Seo, former Ph.D. students in the Huh lab, Alex Yi and Matthew Osborn, then research technicians in the Huh lab, and Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in the Department of Materials Science and Engineering. Lab members Farid Alisafaei and Hossein Ahmadzadeh also contributed to the research. The team collaborated with Insu Lee and professors Sun Min Kim and Tae-Joon Jeon of Inha University.

In order to conduct meaningful drug testing with their devices, the research team needed to ensure that cultured structures within the muscle-on-a-chip were as close to the real human tissue as possible. Critically, they needed to capture muscle’s “anisotropic,” or directionally aligned, shape.

“In the human body, muscle cells adhere to specific anchor points due to their location next to ligament tissue, bones or other muscle tissue,” Huh says. “What’s interesting is that this physical constraint at the boundary of the tissue is what sculpts the shape of muscle. During embryonic development, muscle cells pull at these anchors and stretch in the spaces in between, similar to a tent being held up by its poles and anchored down by the stakes. As a result, the muscle tissue extends linearly and aligns between the anchoring points, acquiring its characteristic shape.”

The team mimicked this design using a microfabricated chip that enabled similar anchoring of human muscle cells, sculpting three-dimensional tissue constructs that resembled real human skeletal muscle.

The the full story in Penn Engineering Today.

2021 CAREER Award recipient: Alex Hughes, Assistant Professor in Bioengineering

by Melissa Pappas

Alex Hughes (illustration by Melissa Pappas)

The National Science Foundation’s CAREER Award is given to early-career researchers in order to kickstart their careers in innovative and pivotal research while giving back to the community in the form of outreach and education. Alex Hughes, Assistant Professor in Bioengineering and in Cell and Developmental Biology, is among the Penn Engineering faculty members who have received the CAREER Award this year.

Hughes plans to use the funds to develop a human kidney model to better understand how the development of cells and tissues influences congenital diseases of the kidney and urinary tract.

The model, known as an “organoid,” is a lab-grown piece of human kidney tissue on the scale of millimeters to centimeters, grown from cultured human cells.

“We want to create a human organoid structure that has nephrons, the filters of the kidney, that are properly ‘plumbed’ or connected to the ureteric epithelium, the tubules that direct urine towards the bladder,” says Hughes. “To achieve that, we have to first understand how to guide the formation of the ureteric tubule networks, and then stimulate early nephrons to fuse with those networks. In the end, the structures will look like ‘kidney subunits’ that could potentially be injected and fused to existing kidneys.”

The field of bioengineering has touched on questions similar to those posed by Hughes, focusing on drug testing and disease treatment. Some of these questions can be answered with the “organ-on-a-chip” approach, while others need an even more realistic model of the organ. The fundamentals of kidney development and questions such as “how does the development of nephrons affect congenital kidney and urinary tract anomalies?” require an organoid in an environment as similar to the human body as possible.

“We decided to start with the kidney for a few reasons,” says Hughes. “First, because its development is a beautiful process; the tubule growth is similar to that of a tree, splitting into branches. It’s a complex yet understudied organ that hosts incredibly common developmental defects.

“Second,” he says, “the question of how things form and develop in the kidney has major medical implications, and we cannot answer that with the ‘organ-on-a-chip’ approach. We need to create a model that mimics the chemical and mechanical properties of the kidney to watch these tissues develop.”

The fundamental development of the kidney can also answer other questions related to efficiency and the evolution of this biological filtration system.

“We have the tendency to believe that systems in the human body are the most evolved and thus the most efficient, but that is not necessarily true,” says Hughes. “If we can better understand the development of a system, such as the kidney, then we may be able to make the system better.”

Hughes’ kidney research will lay the foundation for broader goals within regenerative medicine and organ transplantation.

Read the full story in Penn Engineering Today.

Claudia Loebel Appointed Assistant Professor at the University of Michigan

by Mahelet Asrat

Claudia Loebel, MD, PhD (Photo/Mel Evans)

The Department of Bioengineering is proud to congratulate Claudia Loebel, M.D., Ph.D. on her appointment as Assistant Professor in the Department of Materials Science and Engineering at the University of Michigan. Loebel is part of the University of Michigan’s Biological Sciences Scholar program, which recruits junior instructional faculty in major areas of biomedical investigation. Loebel’s appointment will begin in Fall 2021.

Loebel got her M.D. in 2011 from Martin-Luther University in Halle-Wittenberg, Germany and her Ph.D. in Health Sciences and Technology from ETH Zurich, Switzerland in 2016. There she worked under her advisors Professors Marcy Zenobi-Wong from ETH Zurich and David Eglin from AO Research Institute Davos. At Penn, she conducted postdoctoral research in the Polymeric Biomaterials Laboratory of Jason Burdick, Robert D. Bent Professor in Bioengineering, and as a Visiting Research Scholar in the Mauck Laboratory of the McKay Orthopaedic Research Laboratory in the Perelman School of Medicine.

Loebel was awarded a K99/R00 Pathway to Independence Award through the National Institutes of Health (NIH), which supports her remaining time as a postdoc as well as her time as an independent investigator at the University of Michigan. Loebel is excited about training the next generation of scientists and engineers and being part of their journey in becoming independent and diverse thinkers.

Loebel’s research area is inspired by the interface between material science and regenerative engineering and how it can address specific problems related to tissue development, repair, and regeneration. By developing mechanically and strucatally dynamic biomaterials, microfabrication, and matrix manipulation techniques her works aim to recreate complex cell-matrix interactions and model tissue morphogenesis and disease. The ultimate goal of her research is to use these engineered systems to develop and translate more effective therapeutic treatments for diseases such as fibrotic, inflammatory, and congenital disorders. Her lab’s work will initially focus on developing engineering lung alveolar organoids, aiming to build models of acute and chronic pulmonary diseases and for personalized medicine.

Loebel says, “I am grateful to all my Ph.D. and postdoc mentors for their continuous support and especially Jason who, over the last few years, has trained me in becoming an independent scientist and mentor. This transition would not have been possible without such a great mentor team behind me.”

Congratulations Dr. Loebel from everyone at Penn Bioengineering!

Grace Hopper Distinguished Lecture: “Biomanufacturing Vascularized Organoids and Functional Human Tissues” (Jennifer A. Lewis)

We hope you will join us for the 2021 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering. For event links, email ksas@seas.upenn.edu.

Date: Thursday, March 25, 2021
Time: 3:00-4:00 PM EDT

Jennifer A. Lewis

Speaker: Jennifer A. Lewis, Sc.D.
Wyss Professor for Biologically Inspired Engineering
The Wyss Institue
Paulson School of Engineering and Applied Sciences
Harvard University

Title: “Biomanufacturing Vascularized Organoids and Functional Human Tissue”

Following the lecture, join us for a panel discussion “Horizon 2030: Engineering Life & Life in (Bio)Engineering” featuring Dr. Lewis and Penn faculty and moderated by Bioengineering students. Further details here.

Lecture Abstract:
Recent protocols in developmental biology are unlocking the potential for stem cells to undergo differentiation and self-assembly to form “mini-organs”, known as organoids. To bridge the gap from organoid building blocks (OBBs) to therapeutic functional tissues, integrative approaches that combine bottom-up organoid assembly with top-down bioprinting are needed. While it is difficult, if not impossible, to imagine how either organoids or bioprinting alone would fully replicate the complex multiscale features required for organ-specific function – their combination may provide an enabling foundation for de novo tissue manufacturing. My talk will begin by describing our recent efforts to generate organoids in vitro with perfusable microvascular networks that support their viability and maturation. Next, I will describe the generation of 3D vascularized organ-specific tissues by assembling OBBs into a living matrix that supports the embedded printing of macro-vessels by a process known as sacrificial writing in functional tissue (SWIFT).  Though broadly applicable, I will highlight our recent work on kidney, cerebral, and cardiac tissue engineering.

Dr. Lewis Bio:

Jennifer A. Lewis is the Jianming Yu Professor of Arts and Sciences, the Wyss Professor for Biologically Inspired Engineering in the Paulson School of Engineering and Applied Sciences, and a core faculty member of the Wyss Institute at Harvard University. Her research focuses on 3D printing of functional, structural, and biological materials that emulate natural systems. Prior to joining Harvard, Lewis was a faculty member in the Materials Science and Engineering Department at the University of Illinois at Urbana-Champaign, where she served as the Director of the Materials Research Laboratory. Currently, she directs the Harvard Materials Research Science and Engineering Center (MRSEC) and serves the NSF Mathematical and Physical Sciences Advisory Committee.

Lewis has received numerous awards, including the Presidential Faculty Fellow Award, the American Chemical Society Langmuir Lecture Award, the Materials Research Society Medal Award, the American Ceramic Society Sosman and Roy Lecture Awards, and the Lush Science Prize. She is an elected member of the National Academy of Sciences, National Academy of Engineering, National Academy of Inventors, and the American Academy of Arts and Sciences. Her research has enjoyed broad coverage in the popular media. To date, she has co-founded two companies, Voxel8 Inc. and Electroninks, that are commercializing technology from her lab.

Information on the Grace Hopper Lecture:
In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the Grace Hopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral Grace Hopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. Grace Hopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. Grace Hopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.

Penn Engineers’ New Bioprinting Technique Allows for Complex Microtissues

by Evan Lerner

Jason Burdick, Andrew C. Daly and Matthew Davidson

Bioprinting is currently used to generate model tissues for research and has potential applications in regenerative medicine. Existing bioprinting techniques rely on printing cells embedded in hydrogels, which results in low-cell-density constructs that are well below what is required to grow functional tissues. Maneuvering different kinds of cells into position to replicate the complex makeup of an organ, particularly at organlike cell densities, is still beyond their capabilities.

Now, researchers at the School of Engineering and Applied Science have demonstrated a new bioprinting technique that enables the bioprinting of spatially complex, high-cell-density tissues.

Using a self-healing hydrogel that allows dense clusters of cells to be picked and placed in a three-dimensional suspension, the researchers constructed a model of heart tissue that featured a mix of cells that mimic the results of a heart attack.

The study was led by Jason Burdick, Robert D. Bent Professor in the Department of Bioengineering, and Andrew C. Daly, a postdoctoral researcher in his lab. Fellow Burdick lab postdoc Matthew Davidson also contributed to the study, which has been published in the journal Nature Communications.

Even without a bioprinter, groups of cells can be made to clump into larger aggregates, known as spheroids. For Burdick and colleagues, these spheroids represented a potential building block for a better approach to bioprinting.

“Spheroids are often useful for studying biological questions that rely on the cells’ 3D microenvironments or in the construction of new tissues,” says Burdick. “However, we’d like to produce even higher levels of organization by ‘printing’ different kinds of spheroids in specific arrangements and have them fuse together into structurally complex microtissues.”

Read more at Penn Engineering Today.

BE Seminar: “Deconstructing and Reconstructing Human Tissues” (Kelly Stevens)

Kelly Stevens, PhD

Speaker:  Kelly Stevens, Ph.D.
Assistant Professor, Department of Bioengineering and Department of Laboratory Medicine & Pathology
University of Washington

Date: Thursday, January 21, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Deconstructing and Reconstructing Human Tissues”

Abstract:

Although much progress has been made in building artificial human tissues over the past several decades, replicating complex tissue structure remains an enormous challenge. To overcome this challenge, our field first needs to create better three-dimensional spatial maps, or “blueprints” of human tissues and organs. We also need to then understand how these spatial blueprints encode positional processes in tissues. My group is developing new advanced biofabrication technologies to address both of these issues. Here, I will describe some of our work in both attaining transcriptomic maps as well as in controlling spatiogenetic wiring of human artificial tissues.

Bio:

Dr. Kelly Stevens is an Assistant Professor of Bioengineering, and Laboratory Medicine & Pathology at the University of Washington. Dr. Stevens’ research focuses on mapping and building artificial human tissues to treat liver and heart disease. She has made contributions to improve human cell sourcing, vascularization, structure and physiology of human bioartificial tissues. Dr. Stevens has received several awards in recognition of this work, including the NIH New Innovator Award, BMES CMBE Rising Star Award, John Tietze Stem Cell Scientist Award, and Gree Foundation Scholar Award.

Danielle Bassett and Jason Burdick are Among World’s Most Highly Cited Researchers

Danielle Bassett and Jason Burdick
Danielle Bassett and Jason Burdick

The nature of scientific progress is often summarized by the Isaac Newton quotation, “If I have seen further it is by standing on the shoulders of giants.” Each new study draws on dozens of earlier ones, forming a chain of knowledge stretching back to Newton and the scientific giants his work referenced.

Scientific publishing and referencing has become more formal since Newton’s time, with databases of citations allowing for sophisticated quantitative analyses of that flow of information between researchers.

The Institute for Scientific Information and the Web of Science Group provide a yearly snapshot of this flow, publishing a list of the researchers who are in the top 1 percent of their respective fields when it comes to the number of times their work has been cited.

Danielle Bassett, J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering, and Jason Burdick, Robert D. Bent Professor in the department of Bioengineering, are among the 6,389 researchers named to the 2020 list.

Bassett is a pioneer in the field of network neuroscience, which incorporates elements of mathematics, physics,  biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits. Burdick is an expert in tissue engineering and the design of biomaterials for regenerative medicine; by precisely tailoring the microenvironment within these materials, they can influence stem cell differentiation or trigger the release of therapeutics.

Bassett and Burdick were named to the Web of Science’s 2019 Highly Cited Researchers list as well.

Originally posted in Penn Engineering Today.

Using Lung-on-a-chip Technology to Find Treatments for Chlorine Gas Exposure

Huh’s organ-on-a-chip devices contain human cells, allowing for experiments that could not otherwise be practically or ethically performed.

Chlorine gas is a commonly used industrial chemical. It is also highly toxic and potentially deadly; it was used as a chemical weapon in both World War I and the Syrian Civil War and has led to multiple deaths from industrial accidents. Mixing certain household cleaners can also produce the toxic gas, leading to lasting lung injuries for which there are currently no effective treatments.

Now, researchers at Penn Engineering and Penn’s Perelman School of Medicine are collaborating with BARDA, the U.S. Office of Health and Human Services’ Biomedical Advanced Research and Development Authority, to address this need using their lung-on-a-chip technology.

The laboratory of Dan Huh, associate professor in the Department of Bioengineering, has developed a series of organ-on-a-chip platforms. These devices incorporate human cells into precisely engineered microfluidic channels that mimic an organ’s natural environment, providing a way to conduct experiments that would not otherwise be feasible.

Dan Huh
Dan Huh, PhD

Huh’s previous research has involved using a placenta-on-a-chip to study which drugs are able to reach a developing fetus; investigating microgravity’s effect on the immune system by sending one of his chips to the International Space Station; and testing treatments for dry eye disease using an eye-on-a-chip, complete with a mechanical blinking eyelid.

Read the full story on Penn Engineering Today. Media contact Evan Lerner.

Magnetic Field and Hydrogels Could Be Used to Grow New Cartilage

by Frank Otto

MRI Knee joint or Magnetic resonance imaging sagittal view for detect tear or sprain of the anterior cruciate ligament (ACL).

Using a magnetic field and hydrogels, a team of researchers in the Perelman School of Medicine have demonstrated a new possible way to rebuild complex body tissues, which could result in more lasting fixes to common injuries, such as cartilage degeneration. This research was published in Advanced Materials.

“We found that we were able to arrange objects, such as cells, in ways that could generate new, complex tissues without having to alter the cells themselves,” says the study’s first author, Hannah Zlotnick, a graduate student in bioengineering who works in the McKay Orthopaedic Research Laboratory at Penn Medicine. “Others have had to add magnetic particles to the cells so that they respond to a magnetic field, but that approach can have unwanted long-term effects on cell health. Instead, we manipulated the magnetic character of the environment surrounding the cells, allowing us to arrange the objects with magnets.”

In humans, tissues like cartilage can often break down, causing joint instability or pain. Often, the breakdown isn’t in total, but covers an area, forming a hole. Current fixes are to fill those holes in with synthetic or biologic materials, which can work but often wear away because they are not the same exact material as what was there before. It’s similar to fixing a pothole in a road by filling it with gravel and making a tar patch: The hole will be smoothed out but eventually wear away with use because it’s not the same material and can’t bond the same way.

What complicates fixing cartilage or other similar tissues is that their makeup is complex.

“There is a natural gradient from the top of cartilage to the bottom, where it contacts the bone,” Zlotnick explains. “Superficially, or at the surface, cartilage has a high cellularity, meaning there is a higher number of cells. But where cartilage attaches to the bone, deeper inside, its cellularity is low.”

So the researchers, which included senior author Robert Mauck, PhD, director of the McKay Lab and a professor of Orthopaedic Surgery and Bioengineering, sought to find a way to fix the potholes by repaving them instead of filling them in. With that in mind, the research team found that if they added a magnetic liquid to a three-dimensional hydrogel solution, cells, and other non-magnetic objects including drug delivery microcapsules, could be arranged into specific patterns that mimicked natural tissue through the use of an external magnetic field.

Read more at Penn Medicine News.