Week in BioE (August 9, 2018)

Converting Fat to Fight Obesity

White fat stories calories and provides the body with insulation.

There are two types of fat in the human body: brown and white. Brown fat, the “good” fat, is rich in mitochondria, which gives it its brown appearance. Whereas white fat stores calories and acts as an insulator, mitochondria-rich brown fat burns energy to produce heat throughout the body and maintains body temperature. White fat, conversely, uses its stored energy to insulate the body and keep its temperature level. While all fat serves a purpose in the body, an excess of white fat cells causes obesity, a condition affecting one in three adults in the U.S. and the root cause of many potential health problems. Finding ways to convert white fat to brown opens a possibility of treating this problem naturally.

A new study in Scientific Reports proposes a clever way to convert fat types. Professor of Biomedical Engineering Samuel Sia, PhD, of the Columbia University School of Engineering and Applied Science, led a team which developed a method of converting white fat into brown using a tissue-grafting technique. After extracting and converting the fat, it can then be transplanted back into the patient. White fat is hard-wired to convert to brown under certain conditions, such as exposure to cold temperatures, so the trick for Dr. Sia’s team was finding a way to make the conversion last for long periods. The studies conducted with mice suggested that using these methods, newly-converted fat stayed brown for a period of two months.

Dr. Sia’s team will proceed to conduct further tests, especially on the subjects’ metabolism and overall weight after undergoing the procedure, and they hope that eventual clinical trials will result in new methods to treat or even prevent obesity in humans.

Cremins Lab Student Appointed Blavatnik Fellow

Linda Zhou is currently pursuing her MD/PhD in Genomics and Computational Biology under the supervision of Dr. Jennifer Phillips-Cremins.

The Perelman School of Medicine named Linda Zhou, a student in BE’s Cremins Laboratory, a Blavatnik Fellow for the 2018-2019 academic year. The selection process for this award is highly competitive, and Linda’s selection speaks to the excellent quality of her scholarship and academic performance. The fellows will be honored in a special ceremony at the Museum of Natural History in New York City.

Linda received her B.S. in Biophysics and Biochemistry from Yale University and is currently pursuing her M.D./Ph.D. in the Genomics and Computational Biology Program at Penn. “I am honored to be named a Blavatnik Fellow and am extremely excited to continue my graduate studies investigating neurological disorders and the 3D genome,” she said. “This support will be integral to achieving my long term goal of driving scientific discovery that will help treat human disease.”

Linda’s research is overseen by Penn Bioengineering Assistant Professor Jennifer Phillips-Cremins, PhD. “Linda is an outstanding graduate student,” said Dr. Cremins. “It is a true delight to work with her. She is hard working, intelligent, kind, and has extraordinary leadership ability. Her unrelenting search for ground-state truth makes her a shining star.”

The Blavatnik Family Fellowship in Biomedical Research is a new award announced by the Perelman School of Medicine in May of this year. This generous gift from the Blavatnik Family Foundation awards $2 million to six recipients in the Biomedical Graduate Studies Program at Penn for each of the next four years.

Growing Lungs in a Lab

As the demand for lung transplants continues to rise, so does the need for safe and effective transplanted lungs. Bioengineered lungs grown or created in labs are one way of meeting this demand. The problem – as is ever the case with transplants – is the high rate of rejection. The results of success are always better when cells from the patient herself (or autologous cells) are used in the transplanted organ.

Recently Joan Nichols, PhD, Professor of Internal Medicine, and Microbiology and Immunology, at the University of Texas Medical Branch at Galveston, successfully bioengineered the first human lung. Her latest study published in Science Translational Medicine describes the next milestone for Dr. Nichols’ lab: successfully transplanting a bioengineered lung into a pig.

These advances are possible due to Dr. Nichols’ work with autologous cells, continuing the trend of “on demand” medicine (i.e. medicine tailor for a specific patient) which we track on this blog. Dr. Nichols’ particular method is to build the structure of a lung (using the harvested organs of dead pigs in this case), de-cellularize the tissue, and then repopulate it with autologous cells from the intended recipient. This way, the host body recognizes the cells as friendly and the likelihood of acceptance increases. While further study is needed before clinical trials can begin, Dr. Nichols and her team see the results as extremely promising and believe that we are on the way to bioengineered human lungs.

Nanoparticles Combat Dental Plaque

Combine a diet high in sugar with poor oral hygiene habits and dental cavities likely result. The sugar triggers the formation of an acidic biofilm (plaque) on the teeth, eroding the surface. Early childhood dental cavities affect one in every four children in the United States and hundreds of millions more globally. It’s a particularly severe problem in underprivileged populations.

In a study published in Nature Communications this week, researchers led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Science used FDA-approved nanoparticles to effectively disrupt biofilms and prevent tooth decay in both an experimental human-plaque-like biofilm and in an animal model that mimics early-childhood caries.

Dr. David Cormode is Assistant Professor of Radiology and Secondary Faculty in Bioengineering at Penn. His research includes Bioengineering Therapeutics, Devices and Drug Delivery and Biomaterials.

Read the full story at Penn Today. Media contact Katherine Unger Baillie.

Stopping the Flu from Catching On

The flu virus is notoriously contagious, but there may be a way to stop it before it starts. In order for the influenza virus to successfully transport itself into the cells of a human host, it needs a certain protein called hemagglutinin which mediates its entry. By interfering with this vital ingredient, researchers can effectively kill the virus.

A new study in the Proceedings of the National Academy of Sciences discusses a method of disrupting the process by which this protein causes the virus to infect its host cells. This discovery could lead to more effective flu vaccines that target the flu virus at its root, rather than current ones which have to keep up with the ongoing changes and mutations of the virus itself. Indeed, the need for different vaccines to address various “strains” of the flu is moot if a vaccine can stop the virus from infecting people in the first place.

This breakthrough results from grants provided by the NSF, the Welch Foundation, and the NIH to Rice University and Baylor College of Medicine. Lead researchers José Onuchic, PhD, Harry C. and Olga K. Wiess Chair of Physics and Professor of Chemistry and BioSciences at Rice University; Jianpeng Ma, PhD, Professor of Bioengineering at Rice University and Lodwick T. Bolin Professor of Biochemistry at Baylor College of Medicine; and Qinghua Wang, PhD, Assistant Professor of Biochemistry at Baylor College of Medicine. Their team will continue to study the important role proteins play in how the flu virus operates.

People and Places

This week, we congratulate a few new leadership appointments in bioengineering. First, the Georgia Institute of Technology appointed Penn BE alumnus Andréas García, PhD, the new Executive Director of the Parker H. Petit Institute for Bioengineering and Bioscience. In addition to his new role, Dr. García is also the George W. Woodruff School of Mechanical Engineering Regents Professor. He conducts research in biomolecular, cellular, and tissue engineering and collaborates with a number of research centers across Georgia Tech. Dr. García graduated with both his M.S.E. and Ph.D. from the University of Pennsylvania’s Department of Bioengineering.

Secondly, the University of Minnesota Institute for Engineering in Medicine (IEM) named the Distinguished McKnight University Professor John Bischof, PhD, their new director. This follows Dr. Bischof’s recent position as interim director for the IEM. Dr. Bischof earned his Ph.D. in Mechanical Engineering at the University of California at Berkeley, and is currently a faculty member in both the Mechanical Engineering and Biomedical Engineering Departments at the University of Minnesota. Dr. Bischof holds the Carl and Janet Kuhrmeyer Chair in Mechanical Engineering.

At an earlier, but no less impressive, point in his academic career, Tanishq Abraham became the youngest person to graduate with a degree in biomedical engineering. The fifteen year old recently graduated summa cum laude from the University of California, Davis. As part of his graduating research, Abraham – a first-generation Indian-American – designed a device to measure the heart rates of burn victims. Abraham has already been accepted by U.C. Davis for his Ph.D. and plans to continue on to his M.D.

Finally, the work continues to create affordable and well-fitted prosthetics, especially for remote, rural, and underfunded areas both in the U.S. and abroad. Unfortunately, recent studies published by the Centre for Biomedical Engineering at the India Institute of Technology Delhi (IIT) demonstrate the uphill nature of this battle; stating that India alone contains over half a million upper limb amputees. To address this explosive population, researchers and entrepreneurs are using new bioengineering technologies such as digital manufacturing, 3D scanning and printing, and more. The best innovations are those that save time, resources, and money, without sacrificing quality in the prosthetic or patient comfort. Penn Engineering’s Global Biomedical Service (GBS) program similarly responds to this need, as each year students follow an academically rigorous course with a two-week immersive trip to China, where they learn how to create and fit prosthetic limbs for local children in conjunction with Hong Kong Polytechnic University.

Week in BioE (July 31, 2018)

New Data Analysis Methods

Like many other fields, biomedical research is experiencing a data explosion. Some estimates suggest that the amount of data generated from the health sciences is now doubling every eighteen months, and experts expect it to double every seventy-three days by 2020.  One challenge that researchers face is how to meaningfully analyze this data tsunami.

The challenge of interpreting data occurs at all scales, and a recent collaboration shows how new approaches can allow us to handle the volumes of data emerging at the level of individual cells to infer more about how biology “works” at this level.  Wharton Statistics Department researchers Mo Huang and Jingshu Wang (PhD Student and Postdoctoral Researcher, respectively) collaborated with Arjun Raj’s lab in Bioengineering and published their findings in recent issues of Nature Methods and Proceedings of the National Academy of Sciences.  One study focused on a de-noising technique called SAVER to provide more precise data from single cell experiments and significantly improves the ability to detect trends in a dataset, similar to how increasing sample size helps improve the ability to determine differences between experimental groups.  The second method, termed DESCEND, creates more accurate characterization of gene expression that occur in individual cells. Together these two methods will improve data collection for biologists and medical professionals working  to diagnose, monitor, and treat diseased cells.

Dr. Raj’s team contributed data to the cause and acted as consultants on the biological aspects of this research. Further collaboration involved Mingyao Li, PhD, Professor of Biostatistics at the Perelman School of Medicine, and Nancy Zhang, PD, Professor Statistics at the Wharton School. “We are so happy to have had the chance to work with Nancy and Mingyao on analyzing single cell data,” said Dr. Raj. “The things they were able to do with our data are pretty amazing and important for the field.”

Advancements in Biomaterials

This blog features many new biomaterials techniques and substances, and there are several exciting new developments to report this week. First, the journal of Nature Biomedical Engineering published a study announcing a new therapy to treat or even eliminate lung infections, such as those acquired while in hospital or as the result of cystic fibrosis, which are highly common and dangerous. Researchers identified and designed viruses to target and kill the bacteria which causes these infections, but the difficulty of administering them to patients has proven prohibitive. This new therapy, developed by researchers at the Georgia Institute of Technology, is administered as a dry powder directly to the lungs and bypasses many of the delivery problems appearing in past treatments. Further research on the safety of this method is required before clinical trials can begin.

A team at Harvard University published another recent study in Nature Biomedical Engineering announcing their creation of a tissue-engineered scale model of the left human heart ventricle. This model is made from degradable fibers that simulate the natural fibers of heart tissue. Lead investigator Professor Kevin Kit Parker, PhD, and his team eventually hope to build specific models culled from patient stem cells to replicate the features of that patient’s heart, complete with the patient’s unique DNA and any heart defects or diseases. This replica would allow researchers and clinicians to study and test various treatments before applying them to a specific patient.

Lastly, researchers at the Tufts University School of Engineering published in the Proceedings of the National Academy of Sciences on their creation of flexible magnetic composites that respond to light. This material is capable of macroscale motion and is extremely flexible, allowing its adaptation into a variety of substances such as sponges, film, and hydrogels. Author and graduate student Meg Li explained that this material differs from similar substances in its complexity; for example, in the ability for engineers to dictate specific movements, such as toward or away from the light source. Co-author Fiorenzo Omenetto, PhD, suggests that with further research, these movements could be controlled at even more specific and detailed levels.

CFPS: Getting Closer to “On Demand” Medicine

A recent and growing trend in medicine is the move towards personalized or “on demand” medicine, allowing for treatment customized to specific patients’ needs and situations. One leading method is Cell-Free Protein Synthesis (CFPS), a way of engineering cellular biology without using actual cells. CFPS is used to make substances such as medicine, vaccines, and chemicals in a sustainable and portable way. One instance if the rapid manufacture of insulin to treat diabetic patients. Given that many clinics most in need of such substances are found in remote and under-served locations far away from well-equipped hospitals and urban infrastructure, the ability to safely and quickly create and transport these vital substances to patients is vitally important.

The biggest limiting factor to CFPS is difficulty of replicating Glycosylation, a complex modification that most proteins undergo. Glycosylation is important for proteins to exert their biological function, and is very difficult to synthetically duplicate. Previously, achieving successful Glycosylation was a key barrier in CFPS. Fortunately, Matthew DeLisa, PhD, the Williams L. Lewis Professor of Engineering at Cornell University and Michael Jewett, PD, Associate Professor of Chemical and Biological Engineering at Northwestern University, have created a “single-pot” glycoprotein biosynthesis that allows them to make these critical molecules very quickly. The full study was recently published in Nature Communications. With this new method, medicine is one step closer to being fully “on demand.”

People and Places

The Institute of Electrical and Electronics Engineers (IEEE) interviewed our own Penn faculty member Danielle Bassett, PhD, the Edwardo D. Glandt Faculty Fellow and Associate Professor in Bioengineering, for their website. Dr. Bassett, who shares a joint appointment with Electrical Systems Engineering (ESE) at Penn, has published groundbreaking research in Network Neuroscience, Complex Systems, and more. In the video interview (below), Dr. Bassett discusses current research trends in neuroscience and their applications in medicine.

Finally, a new partnership between Case Western Reserve University and Cleveland Clinic seeks to promote education and research in biomedical engineering in the Cleveland area. Cleveland Clinic Lerner Research Institute‘s Chair of Biomedical Engineering, Geoff Vince, PhD, sees this as an opportunity to capitalize on the renown of both institutions, building on the region’s already stellar reputation in the field of BME. Dozens of researchers from both institutions will have the opportunity to collaborate in a variety of disciplines and projects. In addition to professional academics and medical doctors, the leaders of this new partnership hope to create an atmosphere that can benefit all levels of education, all the way down to high school students.

Week in BioE (July 25, 2018)

Advances in Stem Cell Research

Stem cell therapy has been used to treat a variety of conditions.

A paper published this month in Scientific Reports announced a new a strategy for the treatment of segmental bone defects. The new technique, called Segmental Additive Tissue Engineering (or SATE) comes from a team of researchers with the New York Stem Cell Foundation Research Institute (NYSCF). A press release from the NYSCF and an accompanying short video (below) describe the breakthrough technique, which will “[allow] researchers to combine segments of bone engineered from stem cells to create large scale, personalized grafts that will enhance treatment for those suffering from bone disease or injury through regenerative medicine.”

Segmental Additive Tissue Engineering from NYSCF on Vimeo.

Ralph Lauren Senior Investigator Guiseppe Maria de Peppo, PhD, and first author Martina Sladkova, PhD, express their hope that this new procedure will help address some of the limitations of bone grafts, such as immune system rejection, the need for growing bones in pediatric patients, and the difficulty of creating larger bone grafts made from patient stem cells.

Elsewhere in stem cell research, the Spanish Agency for Medicines and Medical Devices has given the company Viscofan BioEngineering approval to start clinical trials for stem cell therapy to treat heart failure. Already a world leader in the market for medical collagen, Viscofan is now turning its research toward using collagen (a protein found in the connective tissue of mammals) to strengthen the weakened heart muscle of those with ischemic cardiomyopathy, a type of heart failure and the leading cause of death in the world. This new “Cardiomesh” project includes collaborators from industry, academia, and hospitals to create this elastic and biodegradable product. Viscofan expects to start clinical trials after the summer of this year, and the full details can be found in Viscofan’s press release.

Federal Grant Supports International Bioengineering Research

The Canadian government awarded a $1.65 million federal grant to two top Canadian universities to develop a center based on engineering RNA. The University of Lethbridge and the Université de Sherbrooke will team up with international collaborators from the United States, Germany, France, Australia, and more and to found and develop the Ribonucleic Acid Bioengineering and Innovation Network Collaborative Research and Training Experience over the next six years. This comes as part of the Canadian government’s CREATE initiative, which awards grants to research teams across the country to support research, innovation, and jobs-creation in the sciences. These two universities are national leaders in the field of RNA research, a diverse and interdisciplinary field. This new network will focus on training of both young academics transitioning to industry and entrepreneurs looking to develop new technologies. This project is led by Hans-Joachim Wieden, PhD, Chemistry and Biochemistry faculty at the University of Lethbridge and an Alberta Innovates Strategic Chair in RNA Bioengineering.

Lehigh University Awarded Grant in Ebola Research

Close to Philadelphia in Allentown, PA, researchers at Lehigh University received a National Science Foundation (NSF) grant to support their research into one of the deadliest of modern diseases, the Ebola virus, which is highly infectious and currently without vaccine or cure. Entitled “TIM Protein-Mediated Ebola Virus-Host Cell Adhesion: Experiments and Models,” the goal of this research is to create a “predictive and quantitative model of the Ebola Virus (EBOV)-host cell interactions at the molecular through single-virus levels.” Building on past research, the investigators ultimately hope to provide the first quantitative study of this type of cell interaction. By studying how EBOV enters the body through healthy cells, the aim is to understand how it works and ultimately develop a technique to stop its entry. The lead investigator, Anand Jagota, PhD, is the current Professor and Founding Chair of Lehigh University’s Bioengineering program.

New Research in Brain Tumor Removal

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded a grant to Fake (Frank) Lu, PhD, Assistant Professor of Biomedical Engineering at the State University of New York (SUNY) at Binghamton in support of his research to design more accurate techniques for the removal of brain tumors. His technique, called Stimulated Raman Scattering or SRS, is a mode of identifying molecules during surgery which can be used to create a highly detailed and accurate image. Dr. Lu’s SRS techniques will improve both the speed of the surgery and the accuracy of the tissue removal. With this grant support, Dr. Lu’s team will collaborate with local universities and hospitals on collecting more data as their next step before making the technology more widely available.

People and Places

Undergraduate students at our neighbor Drexel University received the Robert Noyce Scholarship, an NSF program that supports students seeking their teacher certification in science and math at the middle school level. The co-investigators and undergraduates are from a variety of disciplines and programs across the university, including co-investigator Donald L. McEachron, PhD, Teaching Professor of Biomedical Engineering, Science and Health Systems. The students’ curriculum in the DragonsTeach Middle Years program will combine rigorous preparation for teaching STEM subjects and the foundational knowledge to work with under-served schools.

Another group of students, this time from California State University, Long Beach, used their victory in the university’s annual Innovation Challenge as an opportunity to launch a startup called Artemus Labs. Their first product, “Python,” uses body heat other physical sensations to regulate a prosthetic liner, useful in making sure prosthetic limbs are comfortable for the wearer. The students explained that their idea was driven by need, as few prosthetic manufacturers prioritize such factors as temperature or sweat regulation in the creation of their products.

Finally, the University of Southern California Viterbi School of Engineering has a new Chair of Biomedical Engineering: Professor K. Kirk Shung, PhD. Dr. Shung obtained his doctorate from the University of Washington and joined USC in 2002. With a background in electrical engineering, Dr. Shung’s research focuses on high frequency ultrasonic imaging and transducer development, and has been supported by a NIH grant as well as won multiple awards from the American Institute of Ultrasound in Medicine and the Institute of Electrical and Electronics Engineers (IEEE), among others.

Week in BioE (July 9, 2018)

A New Treatment for Joint Dysfunction

TMD is a common condition affecting movement of the jaw

Medical researchers have long been baffled by the need to find safe and effective treatment for a common condition called temporomandibular joint dysfunction (TMD). Affecting around twenty-five percent of the adult population worldwide, TMD appears overwhelmingly in adolescent, premenopausal women. Many different factors such as injury, arthritis, or grinding of the teeth can lead to the disintegration of or damage to the temporomandibular joint (TMJ), which leads to TMD, although the root cause is not always clear. A type of temporomandibular disorder,  TMD can result in chronic pain in the jaw and ears, create difficulty eating and talking, and even cause occasional locking of the joint, making it difficult to open or close one’s mouth.  Surgery is often considered a last resort because the results are often short-lasting or even dangerous.

The state of TMD treatment may change with the publication of a study in Science Translational Medicine. With contributions from researchers at the University of California, Irvine (UCI), UC Davis, and the University of Texas School of Dentistry at Houston, this new study has successfully implanted engineered discs made from rib cartilage cells into a TMJ model. The biological properties of the discs are similar enough to native TMJ cells to more fully reduce further degeneration of the joint as well as potentially pave the way for regeneration of joints with TMD.

Senior author Kyriacos Athanasiou, PhD, Distinguished Professor of Biomedical Engineering at UCI, states the next steps for the team of researchers include a long-term study to ensure ongoing effectiveness and safety of the implants followed by eventual clinical trials. In the long run, this technique may also prove useful and relevant to the treatment of other types of arthritis and joint dysfunction.

Advances in Autism Research

Currently, diagnosis of autism spectrum disorders (ASD) has been limited entirely to clinical observation and examination by medical professionals. This makes the early identification and treatment of ASD difficult as most children cannot be accurately diagnosed until around the age of four, delaying the treatment they might receive. A recent study published in the journal of Bioengineering & Translational Medicine, however, suggests that new blood tests may be able to identify ASD with a high level of accuracy, increasing the early identification that is key to helping autistic children and their families. The researchers, led by Juergen Hahn, PhD, Professor and Department Head of Biomedical Engineering at the Rensselaer Polytechnic Institute, hope that after clinical trials this blood test will become commercially available.

In addition to work that shows methods to detect autism earlier, the most recent issue of Nature Biomedical Engineering includes a study to understand the possible causes of autism and, in turn, develop treatments for the disease. The breakthrough technology of Cas9 enzymes allowed researchers to edit the genome, correcting for symptoms that appeared in mice which resembled autism, including exaggerated and repetitive behaviors. This advance comes from a team at the University of California, Berkeley, which developed the gene-editing technique known as CRISPR-Gold to treat symptoms of ASD by injecting the Cas9 enzyme into the brain without the need for viral delivery. The UC Berkeley researchers suggest in the article’s abstract that these safe gene-editing technologies “may revolutionize the treatment of neurological diseases and the understanding of brain function.” These treatments may have practical benefits for the understanding and treatment of such diverse conditions as addiction and epilepsy as well as ASD.

Penn Professor’s Groundbreaking Bioengineering Technology

Our own D. Kacy Cullen, PhD, was recently featured in Penn Today for his groundbreaking research which has led to the first implantable tissue-engineered brain pathways. This technology could lead to the reversal of certain neurodegenerative disorders, such as Parkinson’s disease.

With three patents, at least eight published papers, $3.3 million in funding, and a productive go with the Penn Center for Innovation’s I-Corps program this past fall, Dr. Cullen is ready to take this project’s findings to the next level with the creation of a brand new startup company: Innervace. “It’s really surreal to think that I’ve been working on this project, this approach, for 10 years now,” he says. “It really was doggedness to just keep pushing in the lab, despite the challenges in getting extramural funding, despite the skepticism of peer reviewers. But we’ve shown that we’re able to do it, and that this is a viable technology.” Several Penn bioengineering students are involved in the research conducted in Dr. Cullen’s lab, including doctoral candidate Laura Struzyna and recent graduate Kate Panzer, who worked in the lab all four years of her undergraduate career.

In addition to his appointment as a Research Associate Professor of Neurosurgery at the Perelman School of Medicine at the University of Pennsylvania, Dr. Cullen also serves as a member of Penn’s Department of Bioengineering Graduate Group Faculty, and will teach the graduate course BE 502 (From Lab to Market Place) for the BE Department this fall 2018 semester. He also serves as the director for the Center of Neurotrauma, Neurodegeneration, and Restoration at the VA Medical Center.

New Prosthetics Will Have the Ability to Feel Pain

New research from the Department of Biomedical Engineering at Johns Hopkins University (JHU) has found a way to address one of the difficult aspects of amputation: the inability for prosthetic limbs to feel. This innovative electronic dermis is worn over the prosthetic, and can detect sensations (such as pain or even a light touch), which are conveyed to the user’s nervous system, closing mimicking skin. The findings of this study were recently published in the journal Science Robotics.

While one might wonder at the value of feeling pain, both researchers and amputees verify that physical sensory reception is important both for the desired realism of the prosthetic or bionic limb, and also to alert the wearer of any potential harm or damage, the same way that heat can remind a person to remove her hand from a hot surface, preventing a potential burn. Professor Nitish Thakor, PhD, and his team hope to make this exciting new technology readily available to amputees.

People and Places

Women are still vastly outnumbered in STEM, making up only twenty percent of the field, and given the need for diversification, researchers, educators, and companies are brainstorming ways to proactively solve this problem by promoting STEM subjects to young women. One current initiative has been spearheaded by GE Healthcare and Milwaukee School of Engineering University (MSOE) who are partnering to give middle school girls access to programs in engineering during their summer break at the MSOE Summer STEM Camp, hoping to reduce the stigma of these subjects for young women. GE Girls also hosts STEM programs with a number of institutions across the U.S.

The National Science Policy Network (NSPN) “works to provide a collaborative resource portal for early-career scientists and engineers involved in science policy, diplomacy, and advocacy.” The NSPN offers platforms and support including grant funding, internships, and competitions. Chaired and led by emerging researchers and professors from around the country, including biomedical engineering PhD student Michaela Rikard of the University of Virginia, the NSPN seeks to provide a network for young scientists in the current political climate in which scientific issues and the very importance of the sciences as a whole are hotly contested and debated by politicians and the public. The NSPN looks to provide a way for scientists to have a voice in policy-making. This new initiative was recently featured in the Scientific American.

Upon its original founding in 2000, the Bill and Melinda Gates Foundation has included the eradication of malaria as part of its mission, pledging around $2 billion to the cause in the years since. One of its most recent initiatives is the funding of a bioengineering project which targets the type of mosquitoes which carry the deadly disease. Engineered mosquitoes (so-called “Friendly Mosquitoes”) would mate in the wild, passing on a mosquito-killing gene to their female offspring (only females bite humans) before they reach maturity. While previous versions of “Friendly Mosquitoes” have been met with success, concerns have been raised about the potential long-term ecological effects to the mosquito population. UK-based partner Oxitec expects to have the new group ready for trials in two years.

 

Week in BioE (June 26, 2018)

Holy Grail Found

holy grail
Several types of blood cells under scanning electron microscope.

We cover many highly complex innovations here, and many of these innovations solve vexing problems in the healthcare field.  However, sometimes the problems addressed by these innovations are not particularly complex, even if the impact is economically significant. For instance, venipuncture — commonly referred to as a blood draw — is one of the most basic medical procedures and is mainly performed by medical technicians. There are two problems with venipuncture, however. First, either the health specialist might not be very good at drawing blood or the patient might be non-compliant. Second, the sample must be sent to a lab for analysis by someone else days later, making the costs for blood draws high. A device that could combine these procedures has been considered the “holy grail” of blood testing.

Engineers at Rutgers University might have found this holy grail. Reporting in the journal Technology, the engineers, led by Martin L. Yarmush, PhD, Paul & Mary Monroe Chair and Professor in the Department of Biomedical Engineering at Rutgers, describe how they combined robotics and lab-on-chip technology to create a point-of-care blood testing device. In the article, the authors report the testing of their device with a blood-like fluid loaded with microbeads and with model veins. The automated blood draw technique is the same across all patients, and the analysis of blood can occur immediately after isolating the blood, making it safer, faster, and more cost-effective. Animal testing should follow soon, and a longer-term view envisions expansion of the initial model to accommodate different types of blood testing.

Preventing a Water Crisis

One of the looming crises humankind faces is access to clean water. Nearly one third of the human population either lacks access or has threatened access to potable water. The rapid population growth in the southern hemisphere means that this proportion will increase, even as preventable water-borne diseases like cholera take their toll. Solutions such as desalinization or mass purification could provide solutions, but they are currently prohibitively expensive and create environmental problems of their own. Less expensive and less burdensome solutions continue to be sought.

Now, engineering professors from Carnegie Mellon University (CMU) might have identified a solution. Robert Tilton, PhD, and Todd Przybycien, PhD, both Professors in the Departments of Biomedical Engineering and Chemical Engineering at CMU, are lead authors on a new study in ACS Langmuir describing how proteins produced by the drumstick tree — a very hearty tree native to India that is conducive to a broad range of climate and is already widely cultivated for its fruit and oils — could be used to address water scarcity. The authors exploited the knowledge that cationic protein-modified sand can be used to filter water and showed how to engineer drumstick tree proteins to optimize the filtration process. Testing showed that the authors’ engineered filtration system was more effective and might even lend itself to repeated use.

Innovating for Pediatric Care

Penn Health-Tech is one of the newer initiatives here at the University of Pennsylvania dedicated to catalyzing medical device innovation. However, Penn isn’t the only Philadelphia institution dedicating resources to innovation and invention in medical devices. In the June issue of DOTmed HealthCare Business News magazine, Andrew Rich, who is Senior Director of Biomedical Engineering at the Children’s Hospital of Philadelphia (CHOP), discusses the initiatives being undertaken at CHOP to integrate data from medical devices with electronic health records, as well as other projects.

Improving Limb Prosthetics

Prosthetics have provided a solution for amputees for more than a century, and engineering has been the source of many improvements over that time. A significant goal of scientists studying prosthetics has been the ability of patients to control their artificial limbs with their own neuromuscular signals. While progress has been made in this direction with machine learning, many patients have to spend a lot of time “training” their prostheses to react properly to these signals, which can be deeply discouraging to patients who have already experienced trauma.

A possible solution has been suggested by He (Helen) Huang, PhD, Professor of Biomedical Engineering in the joint department of the University of North Carolina and North Carolina State University, and Stephanie Huang, PhD, Research Assistant Professor in the joint department. In a paper newly published in IEEE Transactions on Neural Systems and Rehabilitation Engineering, the professors used the muscle activation patterns of the residual muscles remaining in patients after amputation. They tested their approach in 10 patients and found highly statistically significant improvement in movement accuracy. Testing in more subjects and allowing users longer training periods during testing could both yield even more impressive outcomes.

People and Places

Synthetic biologists at Colorado State University received a $1.7 million grant from the Defense Advanced Research Projects Agency (DARPA) to genetically engineer sporopollenin — a naturally occurring, chemically inert polymer found in pollen grains — to create what they hope will be the world’s strongest material. Early success could lead to another $2 million in DARPA funding in a couple of years. Matt Kipper, PhD, Associate Professor of Chemical and Biological Engineering, is a co-investigator on the grant.

Rose-Hulman Institute of Technology in Terre Haute, Indiana, has announced that it will be adding a new major in engineering design to its curriculum. Patsy Brackin, PhD, Professor of Mechanical Engineering, will lead the new program as director.

Week in BioE (June 19, 2018)

Dolphin Echolocation Could Improve Ultrasound

dolphin echolocationDolphins are among the most intelligent creatures on earth, showing behaviors such as teaching, learning, cooperation, delayed gratification, and other markers of high intelligence. Dolphins communicate vocally with one another, although we aren’t sure exactly what they communicate. While this communication isn’t “language” as humans define it, it uses echolocation — finding objects and orienteering on the basis of reflected sound — which humans don’t use in their communications.

Now, we have new information about dolphin echolocation thanks to an article recently published in the Journal of the Acoustical Society of America by mathematicians and biomedical engineers in Sweden.  On the basis of earlier research finding that dolphin echolocation signals consist of two tones, rather than one, the new study finds that these two tones are emitted at slightly different times and that the sound waves have a Gaussian shape, similar to a bell curve. Using a mathematical algorithm, the authors successfully simulated echolocation signals in the lab.

The findings explain how dolphins use echolocation effectively but could also contribute to more accurate sound-based diagnostic techniques — particularly ultrasound, which relies heavily on methods similar to echolocation to provide images of moving tissues within the body, e.g., prenatal imaging and heart contraction.

Modeling Diseased Blood Vessels for Drug and Device Testing

Drugs and devices require extensive testing before they are approved by regulatory agencies and used to treat human patients. Tissue engineering has helped bridge the gap between a promising idea and its use in a patient by creating technologies that mimic the complex structure of human tissue. Most of these technologies focus on the engineering of healthy tissues and much less on constructing models of diseased tissue. These models of diseased tissue may be useful for designing treatments for diseases and understanding how diseases are caused.

In this light, Marsha W. Rolle, PhD, Associate Professor of Biomedical Engineering at Worcester Polytechnic Institute (WPI), is working to create engineered blood vessels that are already diseased as a way to test possible treatments. With three years of funding from the National Institutes of Health’s National Heart Lung and Blood Institute amounting to nearly $500,000, Dr. Rolle and her research team create these damaged vessels by engineering smooth muscle cells to form tubes 2 mm in diameter. These synthetic vessels are then modified to resemble features of diseases. For example, growth factors attached to microspheres can encourage the growth of tissue in small parts of the vessel wall, eventually becoming areas of narrowing in the vessel. Similarly, other factors could lead to changes in the vessel that resemble aneurysms. In both cases, the function of the microengineered vessel could be measured as the change happens, providing insight into either vascular stenosis or aneurysms, neither of which is possible in humans.

Dr. Rolle’s first step will be to test the damaged engineered vessels with existing medications. If successful, this new technique could be used for testing of new drugs and devices prior to testing in animals.

New Heart Implant Can Deliver Drug

Speaking of damage to the circulatory system, a new article in Nature Biomedical Engineering details how engineers at MIT, Harvard, and Trinity College, Dublin, created a heart implant that can deliver targeted therapy to damaged heart tissue. The authors, led in part by Conor J. Walsh, PhD, and David J. Mooney, PhD, of Harvard, created a device called Therepi, approximately 4 mm in size, which is deployed with a hypodermic. Once placed, a reservoir of medicine within the Therepi treats the damaged heart muscle. In addition, it can be refilled without needing to remove the implant. The Nature Biomedical Engineering study is limited to testing in rats, but the authors see testing in humans in the near future.

Erdős-Rényi Prize for Penn Professor

Danielle S. Bassett, PhD, Eduardo D. Glandt Faculty Fellow and Associate Professor of Bioengineering at the University of Pennsylvania, has been named the 2018 recipient of the Erdős-Rényi Prize in Network Science by the Network Science Society (NetSci). NetSci has recognized Dr. Bassett for “fundamental contributions to our understanding of the network architecture of the human brain, its evolution over learning and development, and its alteration in neurological disease.” Dr. Bassett will receive the award and deliver a lecture on June 14 at the International Conference on Network Science in Paris. She is the seventh scientist and fourth American to receive the prize.

The Erdős-Rényi Prize is awarded annually to a scientist younger than 40 years old for his/her achievements in the field of network science. It is named for the Hungarian mathematicians Paul Erdős, whose surname provided a measurement for research collaboration by academic mathematicians, and Alfréd Rényi, whose work focused on probability and graph theory. In network science, an Erdős-Rényi model is a model for generating random graphs. Dr. Bassett’s research applies the principles of network science in neuroscience, with the intention of understanding the brain better by modeling the networks and circuits of our most complex organ.

People and Places

Two new centers dedicated to health sciences are opening. Western New England University opened its new Center for Global Health Engineering in April, with Michael J. Rust, PhD, Associate Professor of Biomedical Engineering, as the codirector under director Christian Salmon, PhD. Elsewhere, Northwestern University launched a new center — the Center for Advanced Regenerative Engineering — with Guillermo Ameer, PhD, Daniel Hale Williams Professor of Biomedical Engineering and Surgery at Northwestern, as founding director.

Finally, Joseph J. Pancrazio, Ph.D., Professor of Bioengineering at the University of Texas at Dallas and Associate Provost,  has been named Vice President for Research. Before moving to UT Dallas in 2015, Dr. Pancrazio was the founding chair of Bioengineering at George Mason University in Virginia.

Week in BioE (June 7, 2018)

Vision of the Future

corneal transplantation
A human eye that received a cornea transplant one year postoperatively.

Disorders of or damage to the cornea — the clear covering over the lens of the eye — can be threatening to vision, and for the last century, corneal transplantation has been a cornerstone of treatment for these conditions. However, corneal transplants are complicated by two key facts: first, as with virtually all transplant procedures, donor organs are in short supply; and second, rejection is common, and recipients of transplants face repeated procedures or a lifetime of steroid eyedrops to prevent rejection.

One way of obviating these issues is the use of synthetic materials, which can now be manufactured with three-dimensional printing. In a new study from scientists at the Institute of Genetic Medicine at Newcastle University in the UK, to be published this summer in Experimental Eye Research, synthetic corneal tissue was 3D printed using a bioink loaded with encapsulated keratocytes (corneal cells), in combination with computer modeling based on actual corneas. The study is only proof to show that printing a biological replicate of the cornea is possible, but it lays the groundwork for future studies in animals.

Engineering Brain Recovery

One of the reasons why stroke is such a damaging event is the inability of damaged brain tissue to regenerate. Angiogenesis, the growth of new blood vessels, can help to regenerate brain tissue but properly guiding the process of angiogenesis is rather difficult.

However, a new report in Nature Materials indicates success using an injectable biogel for this purpose. In the report, a team led by Tatiana Segura, PhD, Professor of Biomedical Engineering at Duke with colleagues at UCLA, details its engineering of an injectable gel using nanoparticles consisting of heparin (a blood-thinning agent to prevent unwanted blood clotting) and vascular endothelial growth factor (VEGF) to stimulate brain regeneration. After injecting the gel in a mouse model of stroke, the mice showed a significant improvement in recovery compared to animals not receiving the engineered nanomaterial.

Here at Penn, D. Kacy Cullen, PhD, Research Associate Professor of Neurosurgery in the Perelman School of Medicine, has been investigating the use of implantable tissue-engineered brain pathways to treat and perhaps reverse the effects of neurodegnerative diseases like Parkinson’s disease. Penn Today has the story, with video of Dr. Cullen and photos and quotes from several of our own Bioengineering students.

Streamlining Environmental Bioengineering

Outside of the health sciences, bioengineering has applications in diverse fields, including energy development and environmental protection. Biofuels are one application for bioengineering that received a major boost recently. In an article published in NPJ Systems Biology and Applications, engineers from the US Department of Energy’s Lawrence Berkeley National Laboratory describe how they used machine learning to better predict the ability of engineered microbes to produce biofuel. With this information, they can then better adjust fuel-producing microbial pathways to maximize production. The machine learning model is a significant improvement over earlier, traditionally algorithmic approaches requiring complex differential equations. The time saved could, over generations of adjustments, result in a significant increase in output.

More on Pilots

Last week, we discussed how the cognitive load borne by airline pilots differs between simulated and real flight. Other scientists, it turns out, are looking at ways that pilots — in particular, fighter pilots — can overcome fatigue. With more than $1 million in grants from the US Department of Defense, Merhavan Singh, PhD, Dean of the Graduate School of Biomedical Sciences at the University of North Texas Health Science Center, and  Kai Shen, PhD, Associate Professor in the  Department of Chemistry and Forensic Science at Savannah State University in Georgia, are investigating compounds targeting the sigma 1 receptor, which the scientists believe could combat fatigue and also have neuroprotective effects if activated. This is particularly important among fighter pilots serving in conflict, who are often sleep deprived but must remain alert during missions.

People and Places

Having achieved success in its mission, the University of Alabama at Birmingham’s PREP Scholars Program, which supports underrepresented minority students in pursuing graduate study in bioengineering and biomedical engineering, has received an additional $1.8 million in support from the National Institutes of Health. The money will enable the funding of 40 students over the next five years.

Jeffrey Collins Wolchok, PhD, and Kartik Balachandran, PhD, both associate professors in the Department of Biomedical Engineering at the University of Arkansas, have received a $375,000 grant from the National Science Foundation to study the long-term effects of multiple concussions on the brain. With the increased emphasis in the scientific community and media on traumatic brain injury and chronic traumatic encephalopathy, including among former athletes, the two scientists will develop brain on a chip technology to examine the issue.

Finally, this week, the Best College Reviews website published its Top 10 list of online Master’s programs in biomedical engineering. Purdue University’s program finished in first place, with appearances on the list by Colorado State, UC Riverside, Stevens Tech, and Worcester Tech.

Week in BioE (May 29, 2018)

Virtual Biopsy for Melanoma

virtual biopsy
Melanoma cells stained to show cell nuclei (blue), podosomes (yellow), actin (red), and an actin regulator (green).

Melanoma is a common form of skin cancer that is most often successfully treated by removal of the cancerous cells. However,  malignant forms of melanoma can metastasize and become deadly. The significance of malignant melanoma is evident in its incidence – melanoma is the fifth most common cause of deaths from cancer in the US. Treating melanoma relies on using biopsy samples to determine the virulence of the cancer. However, the biopsy process is invasive and painful, and it can even be disfiguring.

Addressing this issue, Jesse Wilson, PhD, Assistant Professor in the Department of Electrical and Computer Engineering and in the School of Biomedical Engineering at Colorado State University (CSU), is developing a virtual biopsy for the disease. Funded by a Young Investigator Award from the Melanoma Research Alliance and a grant from the Colorado Clinical and Translational Sciences Institute, Dr. Wilson’s virtual biopsy uses multiphoton microscopy, which normally requires the use of a costly short-pulse laser for optimal visualization; his research seeks to obviate the need for laser, thus rendering the process more broadly available. 

Dr. Wilson intends to begin testing of his biopsy device on dogs from CSU’s veterinary school. Dogs also develop malignant melanoma, so the device will be used to gather data about each lesion that a dog develops. Once the imaging data are collected, the dogs will undergo normal biopsy and, if needed, treatment. In parallel, Dr. Wilson’s imaging algorithm will process the microscopy data collected prior to the biopsy, score it as malignant or not, and compare the predictions with the actual biopsy results to determine the new technique’s accuracy.

A Clue to Consciousness

Among the great mysteries in neuroscience is the nature of consciousness — that aspect of our psyche that allows us to observe that we are aware. We know that we have consciousness, but we aren’t sure why we do, nor do we fully understand the biological mechanisms that underlie consciousness.

A new study from scientists at Washington University in St. Louis might offer some clues, however. In the study, published in Neuron, the authors used a combination of calcium and hemoglobin imaging in mice to detect infra-slow spatiotemporal trajectories — essentially brain waves that are qualitatively different from other traditional electrical activity waves measured in the brain. These new waveforms were much slower than the activity of other traditional activity waves, and they traveled through different areas of the animals’ brains. The direction of the waves, moreover, changed on the basis of the level of consciousness of the mice.

Closer to home (and to humans), in a new article in Frontiers in Human Neuroscience, Hasan Ayaz, PhD, Associate Research Professor in the
School of Biomedical Engineering, Science and Health Systems at Drexel University, in collaboration with scientists from France, reports that the cognitive load of airline pilots differs significantly between pilots in the actual cockpit, compared to those using flight simulators. Dr. Ayaz and his colleagues used functional near infrared spectroscopy (fNIRS) for their comparisons. A future step for this research will be to integrate flight data recordings with the fNIRS data.

3D Printing Now Sweeter

Three-dimensional printing has become a vital resource in tissue engineering. However, the ability of commercial 3D printing technology to produce water-soluble glass — a key compound used in many tissue engineering processes — has been elusive because of the specific properties of the carbohydrates used to create this glass, which do not work with the technology used in available 3D printers.

However, this issue could be closer to a solution. In a new article in Additive Manufacturing, a team of scientists led by Rohit Bhargava, PhD, Founder Professor of Engineering in the Department of Bioengineering at the University of Illinois in Urbana-Champaign, reports that they have solved some of these problems. Using isomalt, a type of sugar alcohol, for their experiments, the authors were able to determine the characteristics inherent in the material necessary for 3D printing, as well as modeling the type of machinery necessary to use isomalt in a 3D printing process. Work on creating the 3D printing model recently published is still under way, but video of a bridge model has been published online here.

Seeing Like a Bat

Earlier this month, CLEO (the Conference on Lasers and Electro-Optics) held its annual meeting in San Jose, with a bioengineering contingent out in full force. Nader Engheta, PhD, the H. Nedwill Ramsey Professor with appointments in the Departments of Bioengineering, Electrical and Systems Engineering, and Materials Science and Engineering, was there and gave an interview with Optics & Photonics News. In the interview, Dr. Engheta discusses, among other things, bioinspired polarization — a developing field that seeks to enable people to see polarized light, which is visible to some animals, such as bats, but not to the human eye.

People and Places

Elon University in North Carolina will expand its current offerings in engineering in the coming year. In addition to a dual-degree program, Elon will offer for the first time an undergraduate degree program in engineering with an available concentration in biomedical engineering.  Sirena Hargrove-Leak, PhD, has been named director of the new program.

Week in BioE (May 22, 2018)

Ultrasound Helmet Provides Perioperative Images

ultrasound helmet
Normal ultrasound image of an infant’s brain

As we’ve mentioned here before, surgery on the brain is particularly difficult because of the limited visibility afforded to the surgical field and the complexity of the organ. Because the brain’s gray matter can be easily damaged, a false move by a surgeon can have a lifetime of consequences. Better visualization during surgery could go a long way toward preventing accidental damage by the surgeon and minimize the removal of healthy brain tissue during tumor removal. However, ultrasound imaging of the brain has remained difficult because of the tendency of ultrasound waves to bounce off the skull.

To help solve this problem, a biomedical engineer at Vanderbilt University  developed an ultrasound helmet to create perioperative ultrasound images of the brain. It could also provide a new variety of platform for brain-machine interfaces. According to Brett Byram, PhD, Assistant Professor of Biomedical Engineering at Vanderbilt, the helmet will eventually combine ultrasound with electroencephalography (EEG) to simultaneously visualize the brain and record its activity.  Dr. Byram used a machine learning-based technique called aperture domain model image reconstruction (ADMIRE) to overcome the technical obstacle of ultrasound waves transmitting through the skull. 

Although the initial thought of how to apply this technology was surgical, Dr. Bryram believes that the ability to detect blood flow to different parts of the brain in real time using ultrasound could facilitate the creation of technologies that would use this blood flow information, smoothed using ADMIRE, and EEG data to communicate with implants or robotic extensions to perform tasks.

A Roach Motel for Cancer

One key to curing cancer is preventing its spread, called metastasis. The mechanisms underlying metastasis are becoming clearer after years of research. Typically, the spread of cancer is the result of cancerous cells shed by a tumor affecting another organ after traveling via the bloodstream or lymphatic system. Unfortunately, sometimes this shedding is caused by the surgical procedure to remove the tumor. Therefore, preventing metastasis requires preventing these cells from circulating during and after the surgical procedure.

At the University of Texas at Arlington (UTA), Liping Tang, Ph.D., Professor of Biomedical Engineering at the University of Texas at Arlington, has patented what he calls a “roach motel” for cancer cells. Dr. Tang’s device, which is implanted under the skin, circulates cells of its own that attract circulating metastatic cells. The result of the device is the trapping of the cancer cells within the device and preventing them from traveling further. In vitro testing has been quite successful in a variety of cancers. Preclinical testing in animals will be the next step.

Injectable Alcohol Sensor Could Augment Treatment Programs

A few weeks ago, we detailed here how a scientist is developing DNA-based drug and alcohol screening tests. Recently a group of bioengineers at the University of California–San Diego (UCSD), led by Drew A. Hall, PhD, Assistant Professor of Electrical and Computer Engineering and an affiliate professor in the Department of Bioengineering at UCSD, has developed an injectable biosensor that can communicate blood alcohol levels to a wearable device. The sensor is a complementary metal–oxide semiconductor approximately 1 square millimeter in size and is designed for implantation under the skin surface. If in vivo testing proves successful, the system could be used as part of holistic approaches to preventing alcohol abuse among recovering alcoholics.

A Temperature-measuring Microscope

If you’ve used a microscope, then you’ve probably noticed that the samples viewed using microscopes are almost always on glass slides placed beneath the lens of the device. Now, in an article recently published in Nature Communications, an engineering team reports on their invention of a slide that can also measure temperature fluctuations in samples while maintaining microscopic imaging capability. Ruogang Zhao, PhD, assistant professor in the University at Buffalo Department of Biomedical Engineering, along with colleagues from our sister Departments of Electrical and Systems Engineering and Materials Science and Engineering here at Penn, coated a normal slide with 20-nanometer layers of gold activated by an external laser. Applications of the technology are numerous, and will be accelerated through mass production of slides, which the authors estimate would cost less than 10 cents each.

People and Places
Two large donations make our news this week. First, the University of Southern California received a $10 million gift from a retired ophthalmologist and his wife. The Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics is being led by Mark S. Humayun, MD, PhD., Professor of Ophthalmology, Biomedical Engineering, and Cell and Neurobiology at USC. Across the country, the University of Maryland School of Medicine will establish the Robert E. Fischell Center for Biomedical Innovation with a $20 million gift from Robert Fischell, an inventor and holder of 200 patents. Distinguished University Professor and founding chair of the Fischell Department of Bioengineering William E. Bentley, PhD, will head the Fischell Center.

Also, it’s May, which means graduate news. Two special congratulations are in order. First, we congratulate Rowan University in New Jersey for graduating its first cohort of three newly minted PhDs in Biomedical Engineering. Also at the University of California at Davis, Tanishq Abraham will graduate next month with a Bachelor’s degree in Biomedical Engineering. In case that doesn’t sound like big news, bear in mind that Tanishq is only 14 years old. Tanisq will continue at Davis in studying in an MD/PhD program, which he hopes to finish before finishing his second decade of life.

Finally, we congratulate Brian Holland, MD, who has been named the new chief of pediatric cardiology at the University of Louisville. Dr. Holland is an alumnus of Penn Bioengineering, graduating summa cum laude in 1996.

Week in BioE (May 10, 2018)

Advances in Cancer Detection

glioblastoma
Tumor-brain-interface in a glioblastoma biopsy specimen.

Among the deadliest and most difficult to treat types of cancer is glioblastoma, an especially aggressive form of brain cancer. Widely available imaging techniques can diagnose the tumor, but often the diagnosis is too late to treat the cancer effectively. Although blood-based cancer biomarkers can provide for earlier detection of cancer, these markers face the difficult task of crossing the blood-brain barrier (BBB), which prevents all but the tiniest molecules from moving from the brain to the bloodstream.

A study recently published in Scientific Reports, coauthored by Hong Chen, PhD, Assistant Professor of Biomedical Engineering at Washington University in St. Louis (WUSTL), reports of successful deployment of a strategy consisting of focused ultrasound (FUS), enhanced green fluorescent protein (eGFP), and systemically injected microbubbles to see if the BBB could be opened temporarily to allow biomarkers to pass from the brain into the bloodstream. The authors used eGFP-activated mouse models of glioblastoma, injecting the microbubbles into the mice and then exposing the mice to varying acoustic pressures of FUS. They found that circulating blood levels of eGFP were several thousand times higher in the FUS-treated mice compared to non-treated mice, which would significantly facilitate the detection of the marker in blood tests.

The method has some way to go before it can be used in humans. For one thing, the pressures used in the Scientific Reports study would damage blood vessels, so it must be determined whether lower pressures would still provide detectable transmission of proteins across the BBB. In addition, the authors must exclude the possibility of FUS unexpectedly enhancing tumor growth.

In other body areas, with easier access from tissue to the bloodstream, engineers have developed a disease-screening pill that, when ingested and activated by infrared light, can indicate tumor locations on optical tomography. The scientists, led by Greg M. Thurber, PhD, Assistant Professor of Biomedical and Chemical Engineering at the University of Michigan, reported their findings in Molecular Pharmaceutics.

The authors of the study used negatively charged sulfate groups to facilitate absorption by the digestive system of molecular imaging agents. They tested a pill consisting of a combination of these agents and found that their model tumors were visible. The next steps will include optimizing the imaging agent dosage loaded into the pill to optimize visibility. The authors believe their approach could eventually replace uncomfortable procedures like mammograms and invasive diagnostic procedures.

Liquid Assembly Line to Produce Drug Microparticles

Pharmaceuticals owe their effects mostly to their chemical composition, but the packaging of these drugs into must be done precisely. Many drugs are encapsulated in solid microparticles, and engineering consistent size and drug loading in these particles is key. However, common drug manufacturing techniques, such as spray drying and ball milling, produce uneven results. 

University of Pennsylvania engineers developed a microfluidic system in which more than ten thousand of these devices run in parallel, all on a silicon-and-glass chip that can fit into a shirt pocket, to produce a paradigm shift in microparticle manufacturing. The team, led by David Issadore, Assistant Professor in the Department of Bioengineering, outlined the design of their system in the journal Nature Communications.

The Penn team first tested their system by making simple oil-in-water droplets, at a rate of more than 1 trillion droplets per hour. Using materials common to current drug manufacturing processes, they manufactured polycapralactone  microparticles at a rate of ‘only’ 328 billion particles per hour. Further testing backed by pharma company GlaxoSmithKline will follow.

Preventing Fungal Infections of Dental Prostheses

Dental prostheses are medical devices that many people require, particularly as they age. One of the chief complications with prostheses is fungal infections, with an alarming rate of two-thirds among people wearing dentures. These infections can cause a variety of problems, spreading to other parts of the digestive system and affecting nutrition and overall well-being. Fungal infections can be controlled in part by mouthwashes, microwave treatments, and light therapies, but none of them have high efficacy.

To address this issue, Praveen Arany, DDS, PhD, Assistant Professor, Department of Oral Biology and Biomedical Engineering at SUNY Buffalo, combined 3D printing technology and polycaprolactone microspheres containing amphotericin-B, an antifungal agent. Initial fabrication of the prostheses is described in an article in Materials Today Communications, along with successful in vitro testing with fungal biofilm. If further testing proves effective, these prostheses could be used in dental patients in whom the current treatments are either ineffective or contraindicated.

People and Places

West Virginia University has announced that it will launch Master’s and doctoral programs in Biomedical Engineering. The programs will begin enrolling students in the fall. The graduate tracks augment a Bachelor’s degree program begun in 2014.