An artist’s illustration of nanoparticles transporting mRNA into a T cell (blue), allowing the latter to express surface receptors that recognize cancer cells (red). (Credit: Ryan Allen, Second Bay Studios)
New cancer immunotherapies involve extracting a patient’s T cells and genetically engineering them so they will recognize and attack tumors. This type of therapy is not without challenges, however. Engineering a patient’s T cells is laborious and expensive. And when successful, the alterations to the immune system immediately make patients very sick for a short period of time, with symptoms including fever, nausea and neurological effects.
Now, Penn researchers have demonstrated a new engineering technique that, because it is less toxic to the T cells, could enable a different mechanism for altering the way they recognize cancer, and could have fewer side effects for patients.
The technique involves ferrying messenger RNA (mRNA) across the T cell’s membrane via a lipid-based nanoparticle, rather than using a modified HIV virus to rewrite the cell’s DNA. Using the former approach would be preferable, as it only confers a temporary change to the patient’s immune system, but the current standard method for getting mRNA past the cell membrane can be too toxic to use on the limited number of T cells that can be extracted from a patient.
Michael Mitchell, Margaret Billingsley, and Carl June
The researchers demonstrated their technique in a study published in the journal Nano Letters. It was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation of bioengineering in the School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.
They collaborated with one of the pioneers of CAR T therapy: Carl June, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and the director of the Parker Institute for Cancer Immunotherapy at the Perelman School of Medicine.
University of Washington Researchers Engineer a New Way to Study Circulatory Obstruction
Capillaries are one of the most important forms of vasculature in our body, as they allow our blood to transfer nutrients to other parts of our body. But for how much effect capillary functionality can have on our health, their small size makes them extremely difficult to engineer into models for a variety of diseases. Now, researchers at the University of Washington led by Ying Zheng, Ph. D., engineered a three-dimensional microvessel model with living cells to study the mechanisms of microcirculatory obstruction involved with malaria.
Rather than just achieving a physical model of capillaries, these researchers created a model that allowed them to study typical flow and motion through capillaries, before comparing it to deficiencies in this behavior involved with diseases like malaria. The shape of the engineered model is similar to that of an hourglass, allowing the researchers to study instances where red blood cell transit may encounter bottlenecks between the capillaries and other vessels. Using multiphoton technology, Zheng and her team created 100mm capillary models with etched-in channels and a collagen base, to closely model the typical size and rigidity of the vessels. Tested with malaria-infected blood cells, the model showed similar circulatory obstructive behavior to that which occurs in patients, giving hope that this model can be transferred to other diseases involving such obstruction, like sickle cell anemia, diabetes, and cardiovascular conditions.
Understanding a Cell Membrane Protein Could Be the Key to New Cancer Treatments
Almost every cell in the body has integrins, a form of proteins, on its membrane, allowing cells to sense biological information from beyond their membranes while also using this feedback information to initiate signals within cells themselves. Bioengineers at the Imperial College of London recently looked at the way another membrane protein, called syndecan-4, interacts with integrins as a potential form of future cancer treatment. Referred to as “cellular hands” by lead researcher of the study Armando del Rio Hernandez, Ph.D., syndecan-4 sometimes controls the development of diseases or conditions like cancer and fibrosis. Hernandez and his team specifically studied the ties of syndecan-4 to yes-associated protein (YAP) and enzyme called P13K, both of which are affiliated with qualities of cancer progression like halted apoptosis or cell stiffening. Knowing this, Hernandez and his team hope to continue research into understanding the mechanisms of syndecan-4 throughout the cell, in search of new mechanisms and targets to focus on with future developments of cancer treatments.
A New Medical Device Could Improve Nerve Functionality After Severe Damage
Serious nerve damage remains difficult to repair surgically, often involving the stretching of nerves for localized damage, or the transfer of healthy nerve cells from another part of the body to fill larger gaps in nerve damage. But these imperfect solutions limit the return of full nerve function and movement to the damaged part of the body, and in more serious cases with large areas of nerve damage, can also risk damage in other areas of the body that healthy nerves are borrowed from for treatment. A new study from the University of Pittsburgh published in Science Translational Medicine led by Kacey Marra, Ph. D., has successfully repaired nerve damage in mice and monkeys using a biodegradable tube that releases growth factors called glial-cell-derived neurotrophic factors over time.
Marra and her team showed that this new device restored nerve function up to 80% in nonhuman primates, where current methods of nerve replacement often only achieve 50-60% functionality restoration. The device might have an easier time getting FDA-approval, since it doesn’t involve the use of stem cells in its repair mechanisms. Hoping to start human clinical trials in 2021, Marra and her team hope that the device will help both injured veterans and typical patients with nerve damage, and see potential future applications in facial nerve damage as well.
A New Computational Model Could Improve Treatments for Cancer, HIV, and Autoimmune Diseases
With cancer, HIV, and other autoimmune diseases, the best treatment options for patients are often determined with trial-and-error methods, leading to prolonged instances of ineffective approaches and sometimes unnecessary side effects. A group of researchers led by Wesley Errington, Ph.D., at the University of Minnesota decided to take a computational approach this problem, in an effort to more quickly and efficiently determine the most appropriate treatment for a given patient. Based on parameters controlling interactions between molecules with multiple binding sites, the team’s new model looks primarily at binding strength, linkage rigidity, and size of linkage arrays. Because diseases can often involve issues in molecular binding, the model aimed to model the 78 unique binding configurations for cases of when interacting molecules only have three binding sites, which are often difficult to observe experimentally. This new approach will allow for faster and easier determination of treatments for patients with diseases involving these molecular interactions.
Improved Drug Screening for Glioblastoma Patients
A new microfluidic brain chip from researchers at the University of Houston could help improve treatment evaluations for brain tumors. Glioblastoma patients, who have a five-year survival rate of a little over 5%, are some of the most common patients suffering from malignant brain tumors. This new chip, developed by the lab of Yasemin Akay, Ph.D., can quickly determine cancer drug effectiveness by analyzing a piece of cultured tumor biopsy from a patient by incorporating different chemotherapy treatments through the microfluidic vessels. Overall, Akay and her team found that this new chip holds hope as a future efficient and inexpensive form of drug screening for glioblastoma patients.
People and Places
The brain constructs maps to guide people, not just of physical spaces but also to connect stimuli around them, like conversations and other people. It’s long been known that the brain area responsible for this spatial navigation—the medial temporal lobe—is also involved in recalling memories.
Michael Kahana (left) is principal investigator in the Defense Advanced Research Projects Agency’s RAM program and a professor in the Department of Psychology. Ethan Solomon is an M.D./Ph.D. student in the Department of Bioengineering of the School of Engineering and Applied Science and in the Perelman School of Medicine.
Now, neuroscientists at the University of Pennsylvania have discovered that the signals the brain produces during spatial navigation and episodic memory recall look similar. Low-frequency brain waves called the theta rhythm appear as people jump from one memory to the next, as many prior studies looking only at human navigation have shown. The new findings, which suggest that the brain structures responsible for helping people navigate the world may also “navigate” a mental map of prior experiences, appear in the Proceedings of the National Academy of Sciences.
The Florida Institute of Technology recently announced plans to start construction in spring 2020 on a new Health Sciences Research Center, set to further establish biomedical engineering and pre-medical coursework and research at the institute. With plans to open the new center in 2022, Florida Tech anticipates increased enrollment in the two programs, and hopes that the center will offer more opportunities in a growing professional field.
Anson Ong, Ph.D., the Associate Dean of Administration and Graduate Programs at the University of Texas at San Antonio, was recently elected to the International College of Fellows of Biomaterials Science and Engineering. With a focus on research in biomaterial implants for orthopaedic applications, Ong’s election to the college honors his advancement and contribution to the field of biomaterials research.
Positive results in first-in-U.S. trial of CRISPR-edited immune cells
3D render of the CRISPR-Cas9 genome editing system
Genetically editing a cancer patient’s immune cells using CRISPR/Cas9 technology, then infusing those cells back into the patient appears safe and feasible based on early data from the first-ever clinical trial to test the approach in humans in the United States. Researchers from the Abramson Cancer Center have infused three participants in the trial thus far—two with multiple myeloma and one with sarcoma—and have observed the edited T cells expand and bind to their tumor target with no serious side effects related to the investigational approach. Penn is conducting the ongoing study in cooperation with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics.
“This trial is primarily concerned with three questions: Can we edit T cells in this specific way? Are the resulting T cells functional? And are these cells safe to infuse into a patient? This early data suggests that the answer to all three questions may be yes,” says the study’s principal investigator Edward A. Stadtmauer, section chief of Hematologic Malignancies at Penn. Stadtmauer will present the findings next month at the 61st American Society of Hematology Annual Meeting and Exposition.
Tulane researchers join NIH HEAL initiative for research into opioid crisis
A Tulane University professor and researcher of biomedical engineering will join fellow researchers from over 40 other institutions in the National Institute of Health’s Help to End Addiction Long-Term (HEAL) Initiative. Of the $945 million that make up the project, Michael J. Moore, Ph.D. will receive a share of $1.2 million to advance research in modeling human pain through computer chips, with the help of fellow Tulane researchers Jeffrey Tasker, Ph.D., and James Zadina, Ph.D., each with backgrounds in neuroscience.
Because of the opioid epidemic sweeping the nation, Moore notes that there’s a rapid search going on to develop non-addictive painkiller options. However, he also sees a gap in adequate models to test those new drugs before human clinical trials are allowed to take place. Here is where he hopes to step in and bring some innovation to the field, by integrating living human cells into a computer chip for modeling pain mechanisms. Through his research, Moore wants to better understand not only how some drugs can induce pain, but also how patients can grow tolerant to some drugs over time. If successful, Moore’s work will lead to a more rapid and less expensive screening option for experimental drug advancements.
New machine learning-assisted microscope yields improved diagnostics
Researchers at Duke University recently developed a microscope that uses machine learning to adapt its lighting angles, colors, and patterns for diagnostic tests as needed. Most microscopes have lighting tailored to human vision, with an equal distribution of light that’s optimized for human eyes. But by prioritizing the computer’s vision in this new microscope, researchers enable it to see aspects of samples that humans simply can’t, allowing for a more accurate and efficient diagnostic approach.
Led by Roarke W. Horstmeyer, Ph.D., the computer-assisted microscope will diffuse light through a bowl-shaped source, allowing for a much wider range of illumination angles than traditional microscopes. With the help of convolutional neural networks — a special kind of machine learning algorithm — Horstmeyer and his team were able to tailor the microscope to accurately diagnose malaria in red blood cell samples. Where human physicians typically perform similar diagnostics with a rate of 75 percent accuracy, this new microscope can do the same work with 90 percent accuracy, making the diagnostic process for many diseases much more efficient.
Case Western Reserve University researchers create first-ever holographic map of brain
A Case Western Reserve University team of researchers recently spearheaded a project in creating an interactive holographic mapping system of the human brain. The design, which is believed to be the first of its kind, involves the use of the Microsoft HoloLens mixed reality platform. Lead researcher Cameron McIntyre, Ph.D., sees this mapping system as a better way of creating holographic navigational routes for deep brain stimulation. Recent beta tests with the map by clinicians give McIntyre hope that the holographic representation will help them better understand some of the uncertainties behind targeted brain surgeries.
More than merely providing a useful tool, McIntyre’s project also brings together decades’ worth of neurological data that has not yet been seriously studied together in one system. The three-dimensional atlas, called “HoloDBS” by his lab, provides a way of finally seeing the way all of existing neuro-anatomical data relates to each other, allowing clinicians who use the tool to better understand the brain on both an analytical and visual basis.
Implantable cancer traps reduce biopsy incidence and improve diagnostic
Biopsies are one of the most common procedures used for cancer diagnostics, involving a painful and invasive surgery. Researchers at the University of Michigan are trying to change that. Lonnie Shea, Ph.D., a professor of biomedical engineering at the university, worked with his lab to develop implants with the ability to attract any cancer cells within the body. The implant can be inserted through a scaffold placed under the patient’s skin, making it a more ideal option than biopsy for inaccessible organs like lungs.
The lab’s latest work on the project, published in Cancer Research, details its ability to capture metastatic breast cancer cells in vivo. Instead of needing to take biopsies from areas deeper within the body, the implant allows for a much simpler surgical procedure, as biopsies can be taken from the implant itself. Beyond its initial diagnostic advantages, the implant also has the ability to attract immune cells with tumor cells. By studying both types of cells, the implant can give information about the current state of cancer in a patient’s body and about how it might progress. Finally, by attracting tumor and immune cells, the implant has the ability to draw them away from the area of concern, acting in some ways as a treatment for cancer itself.
People and Places
Cesar de la Fuente-Nunez, PhD
The Philadelphia Inquirer recently published an article detailing the research of Penn’s Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, Cesar de la Fuente, Ph.D. In response to a growing level of worldwide deaths due to antibiotic-resistant bacteria, de la Fuente and his lab use synthetic biology, computation, and artificial intelligence to test hundreds of millions of variations in bacteria-killing proteins in the same experiment. Through his research, de la Fuente opens the door to new ways of finding and testing future antibiotics that might be the only viable options in a world with an increasing level of drug-resistant bacteria
Emily Eastburn, a Ph.D. candidate in Bioengineering at Penn and a member of the Boerckel lab of the McKay Orthopaedic Research Laboratory, recently won the Ashton fellowship. The Ashton fellowship is an award for postdoctoral students in any field of engineering that are under the age of 25, third-generation American citizens, and residents of either Pennsylvania or New Jersey. A new member of the Boerckel lab, having joined earlier this fall, Eastburn will have the opportunity to conduct research throughout her Ph.D. program in the developmental mechanobiology and regeneration that the Boerckel lab focuses on.
The researchers’ experiments involved making synthetic tissues with artificial “cells.” The fibrin network that surrounds these beads pull on them when compressed; by changing the number of beads in their experimental tissues, the researchers could suss out how cell-fiber interplay contributes to the tissue’s overall properties.
Tissue gets stiffer when it’s compressed. That property can become even more pronounced with injury or disease, which is why doctors palpate tissue as part of a diagnosis, such as when they check for lumps in a cancer screening. That stiffening response is a long-standing biomedical paradox, however: tissue consists of cells within a complex network of fibers, and common sense dictates that when you push the ends of a string together, it loosens tension, rather than increasing it.
Now, in a study published in Nature, University of Pennsylvania’s School of Engineering and Applied Science researchers have solved this mystery by better understanding the mechanical interplay between that fiber network and the cells it contains.
The researchers found that when tissue is compressed, the cells inside expand laterally, pulling on attached fibers and putting more overall tension on the network. Targeting the proteins that connect cells to the surrounding fiber network might therefore be the optimal way of reducing overall tissue stiffness, a goal in medical treatments for everything from cancer to obesity.
Paul Janmey and Vivek Shenoy
The study was led by Paul Janmey, Professor in the Perelman School of Medicine’s Department of Physiology and in Penn Engineering’s Department of Bioengineering, and Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in Penn Engineering’s Department of Materials Science and Engineering, Mechanical Engineering and Applied Mechanics, and Bioengineering, along with Anne van Oosten and Xingyu Chen, graduate students in Janmey’s and Shenoy’s labs. Van Oosten is now a postdoctoral fellow at Leiden University in The Netherlands.
Shenoy is Director of Penn’s Center for Engineering Mechanobiology, which studies how physical forces influence the behavior of biological systems; Janmey is the co-director of one of the Center’s working groups, organized around the question, “How do cells adapt to and change their mechanical environment?”
Together, they have been interested in solving the paradox surrounding tissue stiffness.
The blue circle is the global symbol for diabetes. Wikimedia Commons.
Diabetes is one of the more common diseases among Americans today, with the American Diabetes Association estimating that approximately 9.5 percent of the population battles the condition today. Though symptoms and causes may vary across types and patients, diabetes generally results from the body’s inability to produce enough insulin to keep blood sugar levels in check. A new experimental treatment from the lab of Sha Jin, Ph.D., a biomedical engineering professor at Binghamton University, aims to use about $1.2 million in recent federal grants to develop a method for pancreatic islet cell transplantation, as those are the cells responsible for producing insulin.
But the catch to this new approach is that relying on healthy donors of these islet cells won’t easily meet the vast need for them in diabetic patients. Sha Jin wants to use her grants to consider the molecular mechanisms that can lead pluripotent stem cells to become islet-like organoids. Because pluripotent stem cells have the capability to evolve into nearly any kind of cell in the human body, the key to Jin’s research is learning how to control their mechanisms and signaling pathways so that they only become islet cells. Jin also wants to improve the eventual culture of these islet cells into three-dimensional scaffolds by finding ways of circulating appropriate levels of oxygen to all parts of the scaffold, particularly those at the center, which are notoriously difficult to accommodate. If successful in her tissue engineering efforts, Jin will not only be able to help diabetic patients, but also open the door to new methods of evolving pluripotent stem cells into mini-organ models for clinical testing of other diseases as well.
A Treatment to Help Others See Better
Permanently crossed eyes, a medical condition called strabismus, affects almost 18 million people in the United States, and is particularly common among children. For a person with strabismus, the eyes don’t line up to look at the same place at the same time, which can cause blurriness, double vision, and eye strain, among other symptoms. Associate professor of bioengineering at George Mason University, Qi Wei, Ph.D., hopes to use almost $2 million in recent funding from the National Institute of Health to treat and diagnose strabismus with a data-driven computer model of the condition. Currently, the most common method of treating strabismus is through surgery on one of the extraocular muscles that contribute to it, but Wei wants her model to eventually offer a noninvasive approach. Using data from patient MRIs, current surgical procedures, and the outcomes of those procedures, Wei hopes to advance and innovate knowledge on treating strabismus.
A Newly Analyzed Brain Mechanism Could be the Key to Stopping Seizures
Among neurological disorders, epilepsy is one of the most common. An umbrella term for a lot of different seizure-inducing conditions, many versions of epilepsy can be treated pharmaceutically. Some, however, are resistant to the drugs used for treatment, and require surgical intervention. Bin He, Ph. D., the Head of the Department of Biomedical Engineering at Carnegie Mellon University, recently published a paper in collaboration with researchers at Mayo Clinic that describes the way that seizures originating at a single point in the brain can be regulated by what he calls “push-pull” dynamics within the brain. This means that the propagation of a seizure through the brain relies on the impact of surrounding tissue. The “pull” he refers to is of the surrounding tissue towards the seizure onset zone, while the “push” is what propagates from the seizure onset zone. Thus, the strength of the “pull” largely dictates whether or not a seizure will spread. He and his lab looked at different speeds of brain rhythms to perform analysis of functional networks for each rhythm band. They found that this “push-pull” mechanism dictated the propagation of seizures in the brain, and suggest future pathways of treatment options for epilepsy focused on this mechanism.
Hyperspectral Imaging Might Provide New Ways of Finding Cancer
A new method of imaging called hyperspectral imaging could help improve the prediction of cancerous cells in tissue specimens. A recent study from a University of Texas Dallas team of researchers led by professor of bioengineering Baowei Fei, Ph.D., found that a combination of hyperspectral imaging and artificial intelligence led to an 80% to 90% level of accuracy in identifying the presence of cancer cells in a sample of 293 tissue specimens from 102 patients. With a $1.6 million grant from the Cancer Prevention and Research Institute of Texas, Fei wants to develop a smart surgical microscope that will help surgeons better detect cancer during surgery.
Fei’s use of hyperspectral imaging allows him to see the unique cellular reflections and absorptions of light across the electromagnetic spectrum, giving each cell its own specific marker and mode of identification. When paired with artificial intelligence algorithms, the microscope Fei has in mind can be trained to specifically recognize cancerous cells based on their hyperspectral imaging patterns. If successful, Fei’s innovations will speed the process of diagnosis, and potentially improve cancer treatments.
People and Places
A group of Penn engineering seniors won the Pioneer Award at the Rothberg Catalyzer Makerthon led be Penn Health-Tech that took place from October 19-20, 2019. SchistoSpot is a senior design project created by students Vishal Tien (BE ‘20), Justin Swirbul (CIS ‘20), Alec Bayliff (BE ‘20), and Bram Bruno (CIS ‘20) in which the group will design a low-cost microscopy dianostic tool that uses computer vision capabilities to automate the diagnosis of schistosomiasis, which is a common parasitic disease. Read about all the winners here.
Virginia Tech University will launch a new Cancer Research Initiative with the hope of creating an intellectual community across engineers, veterinarians, biomedical researchers, and other relevant scientists. The initiative will focus not only on building better connections throughout departments at the university, but also in working with local hospitals like the Carilion Clinic and the Children’s National Hospital in Washington, D.C. Through these new connections, people from all different areas of science and engineering and come together to share ideas.
Associate Professor of Penn Bioengineering Dani Bassett, Ph.D., recently sat down with the Penn Integrates Knowledge University Professor Duncan Watts, Ph.D., for an interview published in Penn Engineering. Bassett discusses the origins of network science, her research in small-world brain networks, academic teamwork, and the pedagogy of science and engineering. You can read the full interview here.
An all-female group of researchers from Northern Illinois University developed a device for use by occupational therapists that can capture three-dimensional images of a patient’s hand, helping to more accurately measure the hand or wrist’s range of motion. The group presented the abstract for their design at this year’s meeting of the Biomedical Engineering Society here in Philadelphia, where Penn students and researchers presented as well.
New 3D Tumor Models Could Improve Cancer Treatment
New ways of testing cancer treatments may now be possible thanks to researchers at the University of Akron who developed three-dimensional tumor models of triple-negative breast cancer. Led by Dr. Hossein Tavana, Ph. D., an associate professor of biomedical engineering at the university, the Tissue Engineering Microtechnologies Lab recently received a $1.13 million grant from the prestigious National Cancer Institute (NCI) of the National Institute of Health (NIH) to continue improving these tumor models. Tumors are difficult to fully replicate in vitro, as they are comprised of cancerous cells, connective tissue, and matrix proteins, among several other components. With this new grant, Tavana sees creating a high-throughput system that uses many identical copies of the tumor model for drug testing and better understanding of the way tumors operate. This high-throughput method would allow Tavana and his lab to isolate and test several different approaches at once, which they hope will help change the way tumors are studied and treated everywhere.
Noise-Induced Hearing Loss Poses Greater Threat to Neural Processing
Even though we all know we probably shouldn’t listen to music at high volumes, most of us typically do it anyway. But researchers at Purdue University recently found that noise-induced hearing loss could cause significant changes in neural processing of more complex sound inputs. Led by Kenneth Henry, Ph.D., an assistant professor of otolaryngology at the University of Rochester Medical Center, and Michael Heinz, Ph.D., a professor of biomedical engineering at Purdue University, the study shows that when compared with age-related hearing loss, noise-induced hearing loss will result in a greater decrease in hearing perception even when the two kinds of hearing loss appear to be of the same degree on an audiogram. This is because noise-induced hearing loss occurs because of physical trauma to the ear, rather than the long-term electrochemical degradation of some components that come happen with age. The evidence of this research is yet another reason why we should be more careful about exposing our ears to louder volumes, as they pose a greater risk of serious damage.
Increasing the Patient Populations for Research in Cartilage Therapy and Regenration
Despite the great progress in research of knee cartilage therapy and regeneration, there are still issues with the patient populations that most studies consider. Researchers often want to test new methods on patients that have the greatest chance of injury recovery without complications – often referred to as “green knees” – but this leaves out those patient populations who suffer from conditions or defects that have the potential to cause complications – often referred to as “red knees.” In a new paper published in Regenerative Medicine, the Mary Black Ralston Professor for Education and Research in Orthopaedic Surgery and secondary faculty in the Department of Bioengineering at Penn, Robert Mauck, Ph.D., discusses some cartilage therapies that may be suitable for red knee populations.
Working with James Carey, M.D., the Director of the Penn Center for Cartilage Repair and Osteochondritis, Mauck and his research team realized that even those with common knee cartilage conditions such as the presence of lesions or osteoarthritis were liable to be excluded from most regeneration studies. In discussing alternatives methods and structures of studying cartilage repair and regeneration, Mauck and Carey hope that future therapies will be applicable to a wider range of patient populations, and that there will soon be more options beyond full joint replacement for those with red knee conditions.
Plant-Like Superhydrophobicity Has Applications in Biomedical Engineering
Researchers in the Department of Biomedical Engineering at Texas A&M University recently found ways of incorporating the superhydrophobic properties of some plant leaves into biomedical applications through what they’re calling a “lotus effect.” The Gaharwar Lab, led by principal investigator and assistant professor of biomedical engineering Akhilesh Gaharwar, Ph.D., developed an assembly of two-dimensional atomic layers that they describe as a “nanoflower” to help control surface wetting in a biomedical setting. A recent paper published in Chemical Communications describes Gaharwar and his team’s work as expanding the use of superhydrophobic surface properties in biomedical devices by demonstrating the important role that atomic vacancies play in the wetting characteristic. While Gaharwar hopes to research the impact that controlling superhydrophobicity could have in stem cell applications, his work already allows for innovations in self-cleaning and surface properties of devices involving labs-on-a-chip and biosensing.
People and Places
Nader Engheta, H. Nedwill Ramsey Professor in Electrical and Systems Engineering, Bioengineering and Materials Science and Engineering, has been inducted into the Canadian Academy of Engineering (CAE) as an International Fellow. The CAE comprises many of Canada’s most accomplished engineers and Engheta was among the five international fellows that were inducted this year.
The Academy’s President Eddy Isaacs remarked: “Over our past 32 years, Fellows of Academy have provided insights in the fields of education, infrastructure, and innovation, and we are expecting the new Fellows to expand upon these contributions to public policy considerably.”
We would like to congratulate Anthony Lowman, Ph.D., on his appointment as the Provost and Senior Vice President for Academic Affairs at Rowan University. Formerly the Dean of Rowan’s College of Engineering, Lowman helped the college double in size, and helped foster a stronger research community. Lowman also helped to launch a Ph.D. program for the school, and added two new departments of Biomedical Engineering and Experiential Engineering Education in his tenure as the dean. Widely recognized for his research on hydrogels and drug delivery, Lowman was also formerly a professor of bioengineering at Temple University and Drexel University.
Lastly, we would like to congratulate Daniel Lemons, Ph.D., on his appointment as the Interim President of Lehman College of the City University of New York. Lemons, a professor in the Department of Biology at City College, specializes in cardiovascular and comparative physiology, and was also one of the original faculty members of the New York Center for Biomedical Engineering. With prior research funded by both the National Institute of Health (NIH) and the National Science Foundation (NSF), Lemons also holds patents in biomechanics teaching models and mechanical heart simulators.
David Issadore (center) was announced as the awardee of the JPOD @ Philadelphia QuickFire Challenge by Katherine Merton (right), head of JLABS New York City, Boston, and Philadelphia, at last week’s BIO 2019 International convention. (Photo: Johnson & Johnson Innovation)
Chip Diagnostics is a Philadelphia-based device company founded in 2016 based on research from the lab of David Issadore, Assistant Professor of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science. The startup combines microelectronics, microfluidics, and nanomaterials with the aim to better diagnose cancer. The company is developing technologies and digital assays for minimally-invasive early cancer detection and screening that can be done using mobile devices.
There has been a long interest in diagnosing cancer using blood tests by looking for proteins, cells, or DNA molecules shed by tumors, but these tests have not worked well for many cancers since the molecules shed tend to be either nonspecific or very rare.
Issadore’s group aims to target different particles called exosomes: Tiny particles shed by cells that contain similar proteins and RNA as the parent cancer cell. The problem, explains Issadore, is that because of the small size of the exosomes, conventional methods such as microscopy and flow cytometry wouldn’t work. “As an engineering lab, we saw an opportunity to build devices on a nanoscale that could specifically sort the cancer exosomes versus the background exosomes of other cells,” he explains.
After Issadore was approached by the IP group at PCI Ventures in the early stages of their research, Chip Diagnostics has since made huge strides as a company. Now, as the awardee of the JPOD @ Philadelphia QuickFire Challenge, Chip Diagnostics will receive $30,000 in grant funding to further develop the first-in-class, ultra-high-definition exosomal-based cancer diagnostic. The award also includes one year of residency at Pennovation Works as well as access to educational programs and mentoring provided by Johnson & Johnson Family of Companies global network of experts.
Vector Flow Imaging Helps Visualize Blood Flow in Pediatric Hearts
A group of biomedical engineers at the University of Arkansas used a new ultrasound-based imaging technique called vector flow imaging to help improve the diagnosis of congenital heart disease in pediatric patients. The study, led by associate professor of biomedical engineering Morten Jensen, Ph.D., collaborated with cardiologists at the local Children’s Hospital in Little Rock to produce images of the heart in infants to help potentially diagnose congenital heart defects. Though the use of vector flow imaging has yet to be developed for adult patients, this type of imaging could possibly provide more detail about the direction of blood flow through the heart than traditional techniques like echocardiography do. In the future, the use of both techniques could provide information about both the causes and larger effects of heart defects in patients.
Using Stem Cells to Improve Fertility in Leukemia Survivors
One of the more common side effects of leukemia treatment in female patients is infertility, but researchers at the University of Michigan want to change that. Led by associate professor of biomedical engineering Ariella Shikanov, Ph.D., researchers in her lab found ways of increasing ovarian follicle productivity in mice, which directly relates to the development of mature eggs. The project involves the use of adipose-derived stem cells, that can be found in human fat tissue, to surround the follicles in an ovary-like, three-dimensional scaffold. Because the radiation treatments for leukemia and some other cancers are harmful to follicles, increasing their survival rate with this stem cell method could reduce the rate of infertility in patients undergoing these treatments. Furthermore, this new approach is innovative in its use of a three-dimensional scaffold as opposed to a two-dimensional one, as it stimulates follicle growth in all directions and thus helps to increase the follicle survival rate.
Penn Engineers Look at How Stretching & Alignment of Collagen Fibers Help Cancer Cells Spread
Cancer has such a massive impact on people’s lives that it might be easy to forget that the disease originates at the cellular level. To spread and cause significant damage, individual cancer cells must navigate the fibrous extracellular environment that cells live in, an environment that Penn Engineer Vivek Shenoy has been investigating for years.
Shenoy’s most recent study on cancer’s mechanical environment was led by a postdoctoral researcher in his lab, Ehsan Ban. Paul Janmey, professor in Physiology and Bioengineering, and colleagues at Stanford University also contributed to the study. Shenoy also received the Heilmeier Award this March and delivered the Heilmeier Award Lecture in April.
Controlled Electrical Stimulation Can Prevent Joint Replacement Infections
Joint replacements are one of the most common kinds of surgery today, but they still require intense post-operative therapy and have a risk of infection from the replacement implant. These infections are usually due to the inflammatory response that the body has to any foreign object, and can become serious and life-threatening if left untreated. Researchers at the University of Buffalo Jacobs School of Medicine and Biomedical Sciences hope to offer a solution to preventing infections through the use of controlled electrical stimulation. Led by Mark Ehrensberger, Ph.D., Kenneth A. Krackow, M.D., and Anthony A. Campagnari, Ph.D., the treatment system uses the electrical signal to create an antibacterial environment at the interface of the body and the implant. While the signal does not prevent infections completely, these antibacterial properties will prevent infections from worsening to a more serious level. Patented as the Biofilm Disruption Device TM, the final product uses two electrode skin patches and a minimally invasive probe that delivers the electrical signal directly to the joint-body interface. The researchers behind the design hope that it can help create a more standard way of effectively treating joint replacement infections.
People and Places
TBx: Gabriel Koo, Ethan Zhao, Daphne Cheung, and Shelly Teng
For their senior design project, four bioengineering seniors — Gabriel Koo, Ethan Zhao, Daphne Cheung, and Shelly Teng — created a low-cost tuberculosis diagnostic that they called TBx. Using their knowledge of the photoacoustic effect of certain dyes, the platform the group created can detect the presence of lipoarabinomannan in patient urine. The four seniors presented TBx at the Rice360 Design Competition in Houston, Texas this spring, which annually features student-designed low-cost global health technologies.
We hope you will join us for the 2019 Bioengineering Grace Hopper lecture by Dr. Cynthia Reinhart-King.
Date: Thursday, April 4, 2019
Time: 3:30-4:30 PM
Location: Glandt Forum, Singh Center, 3205 Walnut Street
Dr. Cynthia Reinhart-King, Engineering, BME, Photo by Joe Howell
Speaker: Cynthia Reinhart-King, Ph.D.
Cornelius Vanderbilt Professor of Engineering, Director of Graduate Studies, Biomedical Engienering
Vanderbilt University
Title: “Powering Tumor Cell Migration Through Heterogeneous Microenvironments”
Abstract:
To move through tissues, cancer cells must navigate a complex, heterogeneous network of fibers in the extracellular matrix. This network of fibers also provides chemical, structural and mechanical cues to the resident cells. In this talk, I will describe my lab’s efforts to understand the forces driving cell movements in the tumor microenvironment. Combining tissue engineering approaches, mouse models, and patient samples, we create and validate in vitro systems to understand how cells navigate the tumor stroma environment. Microfabrication and native biomaterials are used to build mimics of the paths created and taken by cells during metastasis. Using these platforms, we have described a role for a balance between cellular energetics, cell and matrix stiffness, and confinement in determining migration behavior. Moreover, we have extended this work into investigating the role of the mechanical microenvironment in tumor angiogenesis to show that mechanics guides vessel growth and integrity. I will discuss the mechanical influences at play during tumor progression and the underlying biological mechanisms driving angiogenesis and metastatic cell migration as a function of the ECM with an eye towards potential therapeutic avenues.
Bio:
Cynthia Reinhart-King is the Cornelius Vanderbilt Professor of Engineering and the Director of Graduate Studies in Biomedical Engineering at Vanderbilt University. Prior to joining the Vanderbilt faculty in 2017, she was on the faculty of Cornell University where she received tenure in the Department of Biomedical Engineering. She obtained undergraduate degrees in chemical engineering and biology at MIT and her PhD at the University of Pennsylvania in the Department of Bioengineering as a Whitaker Fellow working with Daniel Hammer. She then completed postdoctoral training as an Individual NIH NRSA postdoctoral fellow at the University of Rochester. Her lab’s research interests are in the areas of cell mechanics and cell migration specifically in the context of cancer and atherosclerosis. Her lab has received funding from the American Heart Association, the National Institutes of Health, the National Science Foundation and the American Federation of Aging Research. She has been awarded the Rita Schaffer Young Investigator Award in 2010 and the Mid-Career Award in 2018 from the Biomedical Engineering Society, an NSF CAREER Award, the 2010 Sonny Yau ‘72 Excellence in Teaching Award, a Cook Award for “contributions towards improving the climate for women at Cornell,” and the Zellman Warhaft Commitment to Diversity Award from the Cornell College of Engineering. She is a fellow of the Biomedical Engineering Society and the American Institute for Medical and Biological Engineering, and she is a New Voices Fellow of the National Academies of Science, Engineering and Medicine. She is currently a standing member of the NIH CMT study section panel and Secretary of the Biomedical Engineering Society.
Information on the GraceHopper 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 GraceHopper 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 GraceHopper 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. GraceHopper 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. GraceHopper 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 to campus 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. The lecture is open to everyone!
Synthetic Spinal Discs from a Penn Research Team Might Be the Solution to Chronic Back Pain
Spinal discs, the concentric circles of collagen fiber found between each vertebra of the spine, can be the source of immense back pain when ruptured. Especially for truck and bus drivers, veterans, and cigarette smokers, there is an increased risk in spinal disc rupture due to overuse or deterioration over time. But these patients aren’t alone. In fact, spinal discs erode over time for almost everyone, and are one of the sources of back pain in older patients, especially when the discs erode so much that they allow direct bone-to-bone contact between two or more vertebrae.
Robert Mauck, Ph.D.
Robert Mauck, Ph.D., who is the director of the McKay Orthopaedic Research Laboratory here at Penn and a member of the Bioengineering Graduate Group Faculty, led a research team in creating artificial spinal discs, with an outer layer made from biodegradable polymer and an inner layer made with a sugar-like gel. Their findings appear in Science Translational Medicine. These synthetic discs are also seeded with stem cells that produce collagen over time, meant to replace the polymer as it degrades in vivo over time. Though Mauck and his time are still far from human clinical trials for the discs, they’ve shown some success in goat models so far. If successful, these biodegradable discs could lead to a solution for back pain that integrates itself into the human body over time, potentially eliminating the need of multiple invasive procedures that current solutions require. Mauck’s work was recently featured in Philly.com.
An Untethered, Light-Activated Electrode for Innovations in Neurostimulation
Neurostimulation, a process by which nervous system activity can be purposefully modulated, is a common treatment for patients with some form of paralysis or neurological disorders like Parkinson’s disease. This procedure is typically invasive, and because of the brain’s extreme sensitivity, even the slightest involuntary movement of the cables, electrodes, and other components involved can lead to further brain damage through inflammation and scarring. In an effort to solve this common problem, researchers from the B.I.O.N.I.C. Lab run by Takashi D.Y. Kozai, Ph. D., at the University of Pittsburgh replaced long cables with long wavelength light and a formerly tethered electrode with a smaller, untethered one.
The research team, which includes Pitt senior bioengineering and computer engineering student Kaylene Stocking, centered the device on the principle of the photoelectric effect – a concept first described in a publication by Einstein as the local change in electric potential for an object when hit with a photon. Their design, which includes a 7-8 micron diameter carbon fiber implant, is now patent pending, and Kozai hopes that it will lead to safer and more precise advancements in neurostimulation for patients in the future.
A New Microfluidic Chip Can Detect Cancer in a Drop of Blood
Many forms of cancer cannot be detected until the disease has progressed past the point of optimum treatment time, increasing the risk for patients who receive late diagnoses of these kinds of cancer. But what if the diagnostic process could be simplified and made more efficient so that even a single drop of blood could be enough input to detect the presence of cancer in a patient? Yong Zeng, Ph.D., and his team of researchers at the University of Kansas in Lawrence sought to answer that question.
They designed a self-assembled 3D-nanopatterned microfluidic chip to increase typical microfluidic chip sensitivity so that it can now detect lower levels of tumor-associated exosomes in patient blood plasma. This is in large part due to the nanopatterns in the structure of the chip, which promote mass transfer and increase surface area, which in turn promotes surface-particle interactions in the device. The team applied the device to their studies of ovarian cancer, one of the notoriously more difficult kinds of cancer to detect early on in patients.
A Wearable Respiration Monitor Made from Shrinky Dinks
Michelle Khine, Ph. D., a professor of biomedical engineering at the University of California, Irvine incorporates Shrinky Dinks into her research. After using them once before in a medical device involving microfluidics, her lab recently worked to incorporate them into a wearable respiration monitor – a device that would be useful for patients with asthma, cystic fibrosis, and other chronic pulmonary diseases. The device has the capability to track the rate and volume of its user’s respiration based on measurements of the strain at the locations where the device makes contact with the user’s abdomen.
Paired with Bluetooth technology, this sensor can feed live readings to a smartphone app, giving constant updates to users and doctors, as opposed to the typical pulmonary function test, which only provides information from the time at which the test takes a reading. Though Khine and her team have only tested the device on healthy patients so far, they look forward to testing with patients who have pulmonary disorders, in hopes that the device will provide more comprehensive and accessible data on their respiration.
People and Places
Ashley Kimbel, a high school senior from Grissom High School in Huntsville, Alabama, designed a lightweight prosthetic leg for local Marine, Kendall Bane, after an attack in Afghanistan led him to amputate one of his legs below the knee. Bane, who likes to keep as active as possible, said the new lighter design is more ideal for activities like hiking and mountain biking, especially as any added weight makes balance during these activities more difficult. Kimbel used a CAD-modeling software produced by Siemens called Solid Edge, which the company hopes to continue improving in accessibility so that more students can start projects like Kimbel’s.
This week, we would like to congratulate Angela Belcher, Ph.D., on being named the new head of the Department of Biological Engineering at the Massachusetts Institute of Technology (MIT). With her appointment to this role, now half of the MIT engineering department heads are women. Belcher’s research is in the overlap of materials science and biological engineering, with a particular focus on creating nanostructures based on the evolution of ancient organisms for applications in medical diagnostics, batteries, solar cells, and more.
We would also like to congratulate Eva Dyer, Ph.D., and Chethan Pandarinath, Ph.D., both of whom are faculty members at the Walter H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, on receiving research fellowships from the Alfred P. Sloan Foundation. Dr. Dyer, who formerly worked with Penn bioengineering faculty member Dr. Konrad Kording while he was at Northwestern University, leads research in the field of using data analysis methods to quantify neuroanatomy. Dr. Pandarinth leads the Emory and Georgia Tech Systems Neural Engineering Lab, where he works with a team of researchers to use properties of artificial intelligence and machine learning to better understand large neural networks in the brain.
Capillaries are one of the most important forms of vasculature in our body, as they allow our blood to transfer nutrients to other parts of our body. But for how much effect capillary functionality can have on our health, their small size makes them extremely difficult to engineer into models for a variety of diseases. Now, researchers at the University of Washington led by 
New ways of testing cancer treatments may now be possible thanks to researchers at the University of Akron who developed three-dimensional tumor models of triple-negative breast cancer. Led by 
A group of biomedical engineers at the University of Arkansas used a 
