How a Diversity Program Enabled a Childhood Orthopaedics Patient’s Research Dreams

by Julie Wood

As a child, Sonal Mahindroo would go to her orthopaedics appointments with her family, slowly becoming more and more fascinated by the workings and conditions of the musculoskeletal system. While being treated for scoliosis, she would receive children’s books from her doctor that helped provide clear and simplified explanations of orthopaedic topics, which supported her interest.

Nearly a decade later, Mahindroo is still interested in expanding her orthopaedic knowledge, and a Penn Medicine program is helping fuel that expansion. Now a senior at St. Bonaventure University in New York, Mahindroo spends her time at the university’s lab. But in addition to that, this year, she was able to take part in more learning opportunities with Penn Medicine’s support, via the McKay Orthopaedic Research Lab’s Diversity, Equity, and Inclusion (DEI) committee’s conference grant program.

McKay’s DEI committee — consisting of faculty, post-docs, graduate students, and staff — offers a welcoming environment and resources that support people of all identities, empowering them to bring forward unique perspectives to orthopaedic research.

“Our goal is to improve diversity and culture both within McKay and in the orthopaedic research community outside of Penn,” said Sarah Gullbrand, PhD, a research assistant professor at the McKay Lab. “We wanted to provide an opportunity for students to attend a conference and make connections to help them pursue their interest in orthopaedic research.”

The McKay conference grant supports undergraduate students who have been unable to get hands-on research experience. Participants are provided with the opportunity to network with leaders in the field of orthopaedic research, listen to cutting-edge research presentations, and learn about ways to get involved in orthopaedic research themselves.

“When launching the conference grant program earlier this year, I was motivated by my own experience attending a conference as an undergraduate. That experience really increased my interest in attending graduate school and taught me a lot about the breadth of research in orthopaedics,” said Hannah Zlotnick, a PhD student at the McKay Lab and member of the DEI committee. Through the McKay Conference Grants, the committee has supported two cohorts of students. “So far, we’ve been able to fund 11 undergraduate students from around the country to virtually attend orthopaedics conferences and receive early exposure to careers in STEM.”

Along with the conference grant, the McKay Lab holds workshops, book clubs, and other programs focused on DEI-related topics. As part of their efforts for promoting gender diversity in the field, the McKay Lab has previously partnered with the Perry Initiative to offer direct orthopaedic experiences for girls in high school, where they can learn how to suture, and perform mock fracture fixation surgeries on sawbones.

As a primarily male-populated field, orthopaedics could benefit greatly from diversity efforts. While women comprise approximately 50 percent of medical school graduates in the United States, they represent only 14 percent of orthopaedic surgery residents.

“The only women on staff at my orthopaedist’s office were receptionists. There were no female physicians or engineers to make my scoliosis brace,” Mahindroo said. “It was really cool coming to the McKay Lab and seeing how much the field has progressed since then.”

Read more at Penn Medicine News.

N.B. Hannah Zlotnick is a PhD student in Bioengineering studying in the lab of Robert Mauck, Mary Black Ralston Professor in Bioengineering and Orthopaedic Surgery.

BE Seminar: “Regenerative Engineering: Enabling Regenerative Medicine” (Guillermo Ameer)

Guillermo Ameer, D.Sc.

Speaker: Guillermo Ameer, D.Sc.
Daniel Hale Williams Professor of Biomedical Engineering & Surgery
McCormick School of Engineering
Northwestern University

Date: Thursday, September 16, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: Regenerative engineering is the convergence of advances in materials science, physical sciences, stem cell and developmental biology, and translational medicine to develop tools that enable the regeneration and reconstruction of tissue and organ function. I will describe how materials can be engineered to play a critical role in treating tissue and organ defects and dysfunction by promoting cellular processes that are conducive to regeneration. Applications of these materials to address the complications of diabetes and orthopaedic injuries will be discussed.

Guillermo Ameer Bio: Dr. Ameer is the Daniel Hale Williams professor of Biomedical Engineering and Surgery in the Biomedical Engineering Department at the McCormick School of Engineering and the Department of Surgery at the Feinberg School of Medicine, Northwestern University. He is the founding director of the Center for Advanced Regenerative Engineering (CARE) and the Director of the NIH-funded Regenerative Engineering Training Program (RE-Training). He received his bachelor’s degree in chemical engineering from The University of Texas at Austin and his doctoral degree in chemical and biomedical engineering from the Massachusetts Institute of Technology. His research interests include regenerative engineering, biomaterials, additive manufacturing for biomedical devices, controlled drug delivery and bio/nanotechnology for therapeutics and diagnostics.

Dr. Ameer’s laboratory pioneered the development and tissue regeneration applications of citrate-based biomaterials (CBB), the core technology behind the innovative bioresorbable orthopaedic tissue fixation devices CITREFIXTM, CITRESPLINETM, and CITRELOCKTM, which were recently cleared by the F.D.A for clinical use and marketed worldwide. CBBs are the first thermoset synthetic polymers used for implantable biodegradable medical devices. The co-founder of several companies, Dr. Ameer has approximately 300 publications and conference abstracts and over 55 patents issued and pending in 9 countries.

His awards include the National Science Foundation CAREER Award, the American Heart Association’s Established Investigator Award, the American Institute of Chemical Engineers (AIChE) Eminent Chemical Engineer Award, the Key to the City of Panama, induction into the Academy of Distinguished Chemical Engineers (U. Texas Mcketta Dept. of Chemical Engineering), and the Society for Biomaterials Clemson Award for Contributions to the Literature. Dr. Ameer is a Fellow of the American Institute of Medical and Biological Engineering (AIMBE), Fellow of the Biomedical Engineering Society (BMES), a Fellow of the AIChE, Fellow of the American Association for the Advancement of Science (AAAS), Fellow of the Materials Research Society, and a Fellow of the National Academy of Inventors. Dr. Ameer is an Associate Editor for the AAAS journal Science Advances and the Regenerative Engineering and Translational Medicine journal; a member of the board of directors of the Regenerative Engineering Society; past board member of BMES and AIMBE; Chair of the AIMBE Awards Committee; Chair-elect of the College of Fellows of AIMBE; and a member of the Scientific Advisory Board of Acuitive Technologies, Inc.- a company that is bringing his biomaterial technologies to the musculoskeletal surgery market.

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!

Modified Nanoparticles Can Stop Osteoarthritis Development

Zhiliang Cheng

As we age, the cushioning cartilage between our joints begins to wear down, making it harder and more painful to move. Known as osteoathritis, this extremely common condition has no known cure; if the symptoms can’t be managed, the affected joints must be surgically replaced.

Now, researchers are exploring whether their specially designed nanoparticles can deliver a new inflammation inhibitor to joints, targeting a previously overlooked enzyme called sPLA2.

Zhiliang Cheng, a research associate professor in the Department of Bioengineering, recently collaborated with members of Penn Medicine’s McKay Orthopaedic Research Laboratory, on a study of this approach, published in the journal Science Advances.

The normal function of sPLA2 is to provide lipids (fats) that promote a variety of inflammation processes. The enzyme is always present in cartilage tissue, but typically in low levels. However, when the researchers examined mouse and human cartilage taken from those with osteoarthritis, disproportionately high levels of the enzyme were discovered within the tissue’s structure and cells.

“This marked increase strongly suggests that sPLA2 plays a role in the development of osteoarthritis,” said the study’s corresponding author, Zhiliang Cheng, PhD, a research associate professor of Bioengineering. “Being able to demonstrate this showed that we were on the right track for what could be a potent target for the disease.”

The next step was for the study team – which included lead author Yulong Wei, MD, a researcher in Penn Medicine’s McKay Orthopaedic Research Laboratory – to put together a nanoparticle loaded with an sPLA2 inhibitor. This would block the activity of sPLA2 enzyme and, they believed, inflammation. These nanoparticles were mixed with animal knee cartilage in a lab, then observed as they diffused deeply into the dense cartilage tissue. As time progressed, the team saw that the nanoparticles stayed there and did not degrade significantly or disappear. This was important for the type of treatment the team envisioned.

Continue reading at Penn Medicine News.

Originally posted in Penn Engineering Today.

“New Biosealant Can Stabilize Cartilage, Promote Healing After Injury”

New research from Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering and Director of Penn Medicine’s McKay Orthopaedic Research Laboratory, announces a “new biosealant therapy may help to stabilize injuries that cause cartilage to break down, paving the way for a future fix or – even better – begin working right away with new cells to enhance healing.” Their research was published in Advanced Healthcare Materials. The study’s lead author was Jay Patel, a former postdoctoral fellow in the McKay Lab and now Assistant Professor at Emory University and was contributed to by Claudia Loebel, a postdoctoral research in the Burdick lab and who will begin an appointment as Assistant Professor at the University of Michigan in Fall 2021. In addition, the technology detailed in this publication is at the heart of a new company (Forsagen LLC) spun out of Penn with support from the Penn Center for Innovation (PCI) Ventures Program, which will attempt to spearhead the system’s entry into the clinic. It is co-founded by both Mauck and Patel, along with study co-author Jason Burdick, Professor in Bioengineering, and Ana Peredo, a PhD student in Bioengineering.

Read the story in Penn Medicine News.

BE/MEAM Seminar: “Microbes in Biomechanics” (Christopher J. Hernandez)

Speaker: Christopher J. Hernandez, Ph.D.
Professor, Sibley School of Mechanical and Aerospace Engineering, Cornell University
Adjunct Scientist, Hospital for Special Surgery

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

Title: “Microbes in Biomechanics”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Mechanical Engineering and Applied Mechanics.

Abstract:

The idea that mechanical stresses influence the growth and form of organs and organisms originated in the 1800s and is the basis for the modern study of biomechanics and mechanobiology. Biomechanics and mechanobiology are well studied in eukaryotic systems, yet eukaryotes represent only a small portion of the diversity and abundance of life on Earth. Bacteria exhibit broad influences on human health (as both pathogens and as beneficial components of the gut microbiome) and processes used in biotechnology and synthetic biology. Over the past eight years my group has explored mechanobiology within individual bacteria and the effects of changes in the composition of commensal bacterial communities on the biomechanics in the musculoskeletal system.

The ability of the bacteria to not only resist mechanical loads (biomechanics) but also to respond to changes in the mechanical environment (mechanobiology) is necessary for survival. Here I describe a novel microfluidic platform used to explore the biomechanics and mechanobiology of individual, live bacteria. I discuss work from my group demonstrating that mechanical stress within the bacterial cell envelope can influence the assembly and function of multicomponent efflux pumps used by bacteria to resist toxins and antibiotics. Additionally, I share some of our more recent work showing that mechanical stress and strain within the bacterial cell envelope can stimulate a bacterial two-component system controlling gene expression. Our findings demonstrate that bacteria, like mammalian cells, have mechanosensitive systems that are key to survival.

In musculoskeletal disease, bacteria are commonly viewed as sources of infection. However, in the past decade the studies by my group and others have suggested that commensal bacteria – the microbiome – can modulate the pathogenesis of musculoskeletal disorders. My group is among the first to study the effects of the gut microbiome on orthopaedic disorders. Here I provide an introduction to the microbiome and current concepts of how modifications to the gut microbiome could influence the musculoskeletal system. Specifically, I discuss studies from my group which are the first to demonstrate that the gut microbiome influences bone biomechanics and the development of infection of orthopaedic implants.

Bio:

Dr. Hernandez is Professor in the Sibley School of Mechanical and Aerospace Engineering at Cornell University and is an Adjunct Scientist at the Hospital for Special Surgery. Dr. Hernandez is a Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the American Society of Mechanical Engineers (ASME), and the American Society for Bone and Mineral Research (ASBMR). He is the 2018 recipient of the Fuller Albright Award for Scientific Excellence from the American Society for Bone and Mineral Research. He has served on the Board of Directors of the Orthopaedic Research Society and the American Society for Bone and Mineral Research. His laboratory’s research currently focuses on the effects of the microbiome on bone and joint disorders, periprosthetic joint infection and the biomechanics and mechanobiology of bacteria.

hernandezresearch.com

Bioengineering Faculty Contribute to New Treatment That “Halts Osteoarthritis-Like Knee Cartilage Degeneration”

A recent study published in Science Translational Medicine announces a discovery which could halt cartilage degeneration caused by osteoarthritis: “These researchers showed that they could target a specific protein pathway in mice, put it into overdrive and halt cartilage degeneration over time. Building on that finding, they were able to show that treating mice with surgery-induced knee cartilage degeneration through the same pathway via the state of the art of nanomedicine could dramatically reduce the cartilage degeneration and knee pain.” This development could eventually lead to treating osteoarthritis with injection rather than more complicated surgery.

Among a team of Penn Engineering and Penn Medicine researchers, the study was co-written by Zhiliang Cheng, Research Associate Professor in Bioengineering, Andrew Tsourkas, Professor in Bioengineering, and Robert Mauck, Mary Black Ralston Professor in Bioengineering and Orthopaedic Surgery. The lead author was Yulong Wei of the Department of Orthopaedic Surgery and the McKay Orthopaedic Research Laboratory.

Read the press release in Penn Medicine News.

Student Spotlight: Sonia Bansal

Sonia Bansal, Ph.D.

Next up in the Penn Bioengineering student spotlight series is Sonia Bansal. Sonia got her B.S. in Biomedical Engineering at Columbia University in 2014. She then came to Penn, where she recently got her Ph.D. in September of 2020 in Bioengineering under the advisement of Robert Mauck, Mary Black Ralston Professor of Orthopaedic Surgery and Professor of Bioengineering. Her dissertation is entitled “Functional and Structural Remodeling of the Meniscus with Growth and Injury” and focuses on the ways the knee meniscus changes while being actively loaded (growth) and under aberrant loading (injurious) conditions. She has presented her work internationally and has first authored four papers, with two more in preparation. She is passionate about K-12 STEM outreach and teaching at the collegiate level. She has been on the teaching team for six classes in the department, and is the first recipient of the Graduate Fellowship for Teaching Excellence from the Bioengineering department.

What drew you to the field of Bioengineering?
I first got interested in Bioengineering when I realized that it would let me merge my interests in biology and the human body with my desire to solve big questions by building and creating solutions. I applied to college knowing it was what I wanted to study.

What kind of research do you conduct, and what is the focus of your thesis?
My research is focused on the knee meniscus, specifically the impacts of its complex extracellular matrix and how that matrix changes during growth and after meniscal injury. My interests are largely translational, and in the future, I’d like to think about how we can use preclinical animal models to create effective therapeutics and drive clinical decision making in the orthopedic space.

What did you study for your undergraduate degree? How does it pair with the work you’re doing now, and what advice would you give to your undergraduate self?
I studied Biomedical Engineering during my undergraduate education and worked in cartilage tissue engineering. These experiences helped guide me to my Ph.D. work here at Penn. The two pieces of advice I’d give my undergraduate self is to ask for help and that it’s important to get more than five hours of sleep a night.

What’s your favorite thing to do on Penn’s campus or in Philly?
My favorite thing to do on campus was to read papers/write lectures/work on grants at a local coffee shop. I used to go to HubBub when it still existed, Saxby’s, and United By Blue.

Have you done or learned anything new or interesting during quarantine?
I have embarked on a journey in culinary fermentation (variety of pickles and sourdough, of course), and recently started homebrewing!

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.

Penn Bioengineering Postdoc Brittany Taylor Appointed Assistant Professor at University of Florida

 

Brittany Taylor, PhD

The Department of Bioengineering is proud to congratulate Postdoctoral Researcher Brittany Taylor, PhD on her appointment as a tenure-track Assistant Professor in the J. Crayton Pruitt Family Department of Biomedical Engineering of the Herbert Wertheim College of Engineering at the University of Florida. Taylor’s appointment will begin in January 2021 after four years as a postdoc in Penn Medicine’s McKay Orthopaedic Research Laboratory where she worked under the supervision of Louis Soslowsky, Fairhill Professor in Orthopaedic Surgery and Professor in Bioengineering.

Taylor got her BS in Biomedical Engineering from the University of Virginia where she conducted research under Drs. Cato Laurencin and Edward Botchwey (the latter got his PhD in Penn Bioengineering in 2002). She went on to complete her PhD in Biomedical Engineering in 2016, studying with Dr. Joseph Freeman, in the Musculoskeletal Tissue Regeneration Laboratory at Rutgers University. During her time at Penn, she served as the Co-President of the Biomedical Postdoctoral Council, worked with the Perelman School of Medicine’s PennVIEW program on postdoctoral diversity recruitment, and spearheaded the mentoring circles program, which brings together postdoctoral researchers, graduate students, and undergraduates in informal groups that allow mentorship and learning to flow freely.

The foundation for Taylor’s research interests is a combination of her training in bone tissue engineering, bioactive biomaterials, and tendon injury and repair. Her graduate research focused on a three-dimensional biomimetic pre-vascularized scaffold that simultaneously promoted osteogenic and angiogenic differentiation of human mesenchymal stem cells in vitro and cellular infiltration and neovascularization in vivo without the addition of growth factors of cells. As a postdoctoral fellow, in addition to investigating the role of collagen type V on tendon inflammation and remodeling in a mouse patellar tendon injury model, she also elucidated the biological and mechanical implications of an implantable bilayer delivery system (BiLDS) for controlled and localized release of non-steroidal anti-inflammatory drugs (NSAIDs) to modulate tendon inflammation in a rat rotator cuff injury and repair model. This collection of work exploits the ability of these transformative technologies to provide physical and chemical regenerative cues without the use of exogenous cells; hence avoiding possible complications associated with autologous and allogeneic cell sources and simplifying the regulatory pathway towards clinical application. Taylor’s future research program at the University of Florida will focus on tailored cell-free combinatorial strategies, such as decellularized matrices, tunable delivery systems, and modified extracellular vesicles, to complement and improve the native musculoskeletal tissue regenerative and reparative process.

“Brittany has been an amazing postdoctoral fellow,” says her mentor Louis Soslowsky. “She has learned a lot and contributed to various projects in an exemplary manner. She has been a leader in many arenas here at Penn and I am so proud of what she has done so far. I look forward to following her continued accomplishments at the University of Florida! I know she’ll do great!”

In the course of her pre-faculty career, Taylor achieved an impressive list of accomplishments. She received a Postdoctoral Fellowship for Academic Diversity from the Office of the Vice Provost for Research; a Postdoctoral Enrichment Program (PDEP) award from the Burroughs Wellcome Fund; and a UNCF Bristol-Myers Squibb E.E. Just Postgraduate Fellowship. Additionally, she was named a Rising Star in Cell Mentor’s list of “100 inspiring Black scientists in America” in February 2020 and was given a Rising Star in Biomedical Science Award from MIT in 2019.

“I am grateful for the opportunity to complete my postdoctoral training at Penn,” Taylor says:

“[P]articularly in a lab that is affiliated with the Penn Bioengineering program and the Department of Orthopaedic Surgery, where I had the unique experience of addressing basic science questions using translational animal models, while utilizing my engineering background and having a direct interaction with clinicians. Additionally, I connected with some amazing people here at Penn who had a significant impact on my time at Penn, and will be lifelong friends, colleagues, and mentors.”

Congratulations Dr. Taylor from everyone at Penn Bioengineering!