Nerve Repair, With Help From Stem Cells

A cross-disciplinary Penn team is pioneering a new approach to peripheral nerve repair.

In a new publication in the journal npj Regenerative Medicine, a team of Penn researchers from the School of Dental Medicine and the Perelman School of Medicine “coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors,” addressing the need for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. The study was led by Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation in the Department of Oral and Maxillofacial Surgery/Pharmacology at the University of Pennsylvania School of Dental Medicine, and was co-authored by D. Kacy Cullen, Associate Professor in Neurosurgery at the Perelman School of Medicine at Penn and the Philadelphia Veterans Affairs Medical Center and member of the Bioengineering Graduate Group:

D. Kacy Cullen (Image: Eric Sucar)

“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.

“The animals that received nerve conduits laden with the infused cells had a performance that matched the group that received an autograft for their repair,” he says. “When you’re able to match the performance of the gold-standard procedure without a second surgery to acquire the autograft, that is definitely a technology to pursue further.”

Read the full story and view the full list of collaborators in Penn Today.

Penn Anti-Cancer Engineering Center Will Delve Into the Disease’s Physical Fundamentals

by Evan Lerner

A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.

Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.

However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.

The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.

Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.

Dennis Discher and Ravi Radhakrishnan

The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.

Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.

Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).

Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).

Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.

Originally posted in Penn Engineering Today.

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.

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!

BE Seminar: “Promoting Appendage/Limb Regeneration in Jellyfish, Drosophila, and Mouse” (Lea Goentoro)

We hope you will join us for our final seminar of the spring semester!

Speaker: Lea Goentoro, Ph.D.
Professor
Biology
California Institute of Technology

Date: Thursday, April 22, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Abstract: Can limb regeneration be induced? In this talk, I will discuss our work to promote regeneration in animals with limited regeneration capacity. I will present our recent discovery of a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.

Lea Goentoro Bio: Lea Goentoro is a Professor of Biology in the Division of Biology and Biological Engineering at the California Institute of Technology. She holds a B.S. in Chemical Engineering from University of Wisconsin, Madison and a Ph.D. in Chemical Engineering from Princeton University. Prior to joining Caltech, she did postdoctoral training in the Department of Systems Biology at Harvard Medical School. Her work has been supported by the Damon-Runyon Cancer Foundation, the James S. McDonnell Foundation, the National Science Foundation, and the National Institute of Health.

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: “Stem Cell Fate is a Touchy Subject” (Quinton Smith, MIT)

The first lecture in the Fall 2020 Penn Bioengineering Seminar Series will be held Thursday, September 10th. All seminars this semester will be held virtually on Zoom.

Quinton Smith, PhD

Speaker: Quinton Smith, Ph.D.
Postdoctoral Fellow
Laboratory for Multiscale Regenerative Technologies
Massachusetts Institute of Technology

Date: Thursday, September 10, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Stem Cell Fate is a Touchy Subject”

Abstract:

The success of regenerative cell therapy relies on the integration of a functional vascular system within the redeveloping tissue, to mediate the exchange of oxygen, nutrients and waste. Although the advent of human induced pluripotent stem cells (hiPSCs) has accelerated progress towards this goal, owing to their potential to generate clinically relevant scales of patient-specific cells, techniques to drive their specification mainly rely on chemical cues. In this seminar, I will discuss engineering strategies to control the complex stem cell extracellular milieu, emphasizing the importance of mechanical cues during hiPSC development, specification and downstream functionality as it relates to vascular differentiation.

Bio:

Quinton Smith received his PhD in Chemical and Biomolecular Engineering from Johns Hopkins University in 2017 after completing his bachelor’s degree in Chemical Engineering from the University of New Mexico. As a graduate student under the guidance of Dr. Sharon Gerecht, Quinton implemented various engineering tools to explore the roles of physical and chemical cues on stem cell lineage specification and downstream maturation. Dr. Smith is currently a postdoctoral fellow under the mentorship of Dr. Sangeeta Bhatia at MIT’s Koch Institute for Integrative Cancer Research, where he is investigating the role biliary epithelium in liver regeneration. Dr. Smith’s predoctoral work was supported by an NIH/NHLBI F-31 and NSF Graduate Research Fellowship. He is a recipient of the 2017 Siebel Scholar award, and most recently joined the class of 2018 HHMI Hanna Gray Fellows.

See the full list of upcoming Penn Bioengineering fall seminars here.

Why This Bioengineering Ph.D. Student Pursued Impact Investing

In a Q&A, Bioengineering doctoral candidate Ana P. Peredo explains how the idea of “regeneration” motivated her to join WIVA, Wharton Social Impact’s impact investing program.

Why would you — a bioengineering Ph.D. student — seek to join WIVA?

As a bioengineering Ph.D. student, Ana P. Peredo is currently working on the development of regenerative methods and drug-delivery approaches for musculoskeletal tissue

“As a high school student, I was motivated to study bioengineering because of its potential to generate impact through technical innovation. To me, bioengineering was a way to apply engineering principles to create medical technology in the hopes of devising solutions for global health concerns.

Though I have gained significant understanding of the current pressing healthcare needs, I felt that I was missing a key understanding of how investors think about social impact. To better understand how to apply my science background to the impact space, I joined WIVA. I also wanted to venture outside of healthcare and learn about other important social impact sectors such as education, energy, and environment, all of which WIVA explores in its deal-sourcing process.”

What have you learned through WIVA that you have not been exposed to before?

“I learned how to assess early-stage startups for their impact and return-on-investment potential, as well as how to rigorously analyze company financials and projections.

I also had the opportunity to meet leading social impact professionals through WIVA. I attended a Wharton Social Impact Initiative event with Vincent Stanley, the Director of Philosophy at Patagonia. From this discussion, I learned about how the word ‘sustainable’ continues to be misused by companies and how companies should try to ‘regenerate’ the resources they consume to be truly deemed sustainable.

This conversation brought to mind my research experience with regeneration — could I use my WIVA deal-sourcing techniques to find impactful startups that use this concept?”

Continue reading at Wharton Stories.

BE Seminar Series: February 6th with Kara Spiller, Ph.D.

We hope you’ll join us for our next Penn Bioengineering seminar!

Kara L. Spiller, Ph.D.

Speaker: Kara Spiller, Ph.D.
Associate Professor of the School of Biomedical Engineering, Science, and Health Systems
Drexel University

Date: Thursday, February 6, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

 

 

Title: “Immunomodulatory Biomaterials for Limb Salvage”

Abstract:

Diabetes and peripheral arterial disease affect hundreds of millions of people worldwide. Patients with these conditions frequently develop chronic wounds on the lower limbs that lead to amputation, with a 5-year mortality rate as high as 77%. Macrophages, the primary cell of the innate immune system, are critical regulators of angiogenesis and wound healing. Their dysfunction is strongly implicated in arterial dysfunction, limb ischemia, and poorly healing chronic wounds. The goal of the Biomaterials and Regenerative Medicine Laboratory at Drexel University is to understand the mechanisms by which macrophages orchestrate successful angiogenesis and tissue regeneration and to develop novel biomaterial strategies that apply these principles to pathological situations, in order to ultimately prevent limb amputation. This talk will focus on the effects of temporal changes in macrophage phenotype on angiogenesis, the design of biomaterials and drug delivery systems to modulate macrophage phenotype for enhanced angiogenesis, and the development of macrophage phenotype-related biomarkers to assist in clinical decision making for a personalized medicine approach to wound care.

Bio:

Dr. Kara Spiller is an Associate Professor in Drexel University’s School of Biomedical Engineering, Science, and Health Systems. Her research interests include the role of immune cells in tissue regeneration, the design of immunomodulatory biomaterials, and international engineering education. Her research is funded by the NIH, the NSF, and private foundations. Her awards include a Fulbright fellowship, the NSF CAREER award, and the United States nomination for the ASPIRE prize.