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.

Week in BioE (May 1, 2018)

To Bee or Not To Bee

beesYou might have heard reporting over the last few years that honeybees are dying at faster-than-usual rates. Over the last decade, colony collapse rates increased significantly, causing precipitous losses in the overall bee population. The consequences could be grave: in addition to providing honey, bee pollination is an important factor in agriculture, affecting major crops such as melons. squashes, and several kinds of nuts. Loss of this factor could substantially increase prices or even result in shortages.

 

To address this crisis, scientists at Washington State University focused on the role played by pesticides in colony collapse disorder. These poisons are particularly toxic to bees in tiny amounts, with the problem compounded by the ability of these toxins to build up in the bees’ bodies. A group of students led by Waled Suliman, PhD, a postdoctoral research associate in WSU’s Department of Biological Systems Engineering, developed a powder that acts like a magnet to draw pesticide out of the insects’ bodies. The bees then excrete the pesticide-laden particles like any other kind of waste.

 

The initiative, called Gaminus, has already tested its material in bees and found that the design works as planned. In coming months, they intend to continue their research by measuring toxin levels in the excreted particles.

Advances in Visualization

An important field within bioengineering is visualization, or the ability to use technology to enable scientists to see biological processes not normally visible to the naked eye. If you’ve seen a fetal ultrasound, for instance, then you’ve seen how one part of this area has advanced enormously in recent years. However, integrating visualization technologies with surgery remains a major challenge, particularly for minimally invasive surgeries. One key obstacle is that surgeons must rely on video screens during surgery, rather than being able to look down and feel the tissue with their hands.

 

A startup at the Cleveland Clinic is attempting to integrate perioperative visualization with HoloLens, a brand of smart glasses developed by Microsoft, to produce “mixed reality,” i.e., a combination of actual vision and virtual reality. With a grant from the National Heart, Lung, and Blood Institute awarded to Centerline Biomedical, the Cleveland Clinic startup, and to Karl West, Director of Medical Device Solutions at Cleveland Clinic and a staff member in the Lerner Research Institute’s Department of Biomedical Engineering, the integrated visualization device will be tested in a preclinical model of cardiac stent placement.

 

Elsewhere in the Midwest, Nathan Gianneschi, PhD, Professor of Chemistry, Biomedical Engineering and Materials Science and Engineering at Northwestern University, has been leading an effort to augment transmission electron microscopy (TEM). In its common form, TEM provides highly detailed images of submicroscopic organisms and structures and can provide visualization of nanomaterials as they grow. Gianneschi’s new approach, called liquid cell TEM (LCTEM), uses an irradiated region of a liquid cell to facilitate real-time visualization. The work is detailed in a recent article in ACS Central Science. You can see video posted online at the journal website.

Turning Red

Ultraviolet and infrared light appear beyond either end of the visible light spectrum. Past work using either ultraviolet or infrared light to activate fluorescent proteins can help visualize biochemistry in vivo, but it can also damage cells because of the activating light or the chemicals produced by illuminating the proteins. Recently, Young L. Kim, PhD,  Associate Professor of Biomedical Engineering at Purdue, led a team of scientists who produced red fluorescent silk to kill harmful bacteria when the protein is activated by external green light. Dr. Kim and his colleagues report their findings in Advanced Science. The silk requires further testing, but if ultimately proved successful, it could overcome a current limitation of the use light-activated fluorescent biomaterials in controlling pathogens, which is that the light itself, often in the ultraviolet part of the spectrum, comes with its own potentially negative effects on health.

Absorbable Stents for Cardiac Care

Vascular stents to reopen blocked coronary arteries are usually the treatments used for patients with mild coronary artery disease. These simple devices are a small tube, sometimes coated with a drug to prevent clotting, inserted into the artery to restore flow. Stents can fail over time, requiring reimplantation, and the stents may also narrow over time and reduce blood flow to the surrounding tissue. To overcome this problem, Donghui Zhu, PhD, Associate Professor in the Department of Biomedical Engineering at the University of North Texas, developed a stent that is fully biodegradable and disappears over time as the damaged tissue heals. Dr. Zhu recently won a $2 million grant from the National Institutes of Health to test the stent in a series of trials.

 

People and Places

Penn State University has won a research grant from the American Heart Association, which will be used to support its 10-week Penn State Summer Translational Cardiovascular Science Institute (STCSI). Led by Keefe Manning, PhD, Professor of Biomedical Engineering at Penn State, the STCSI will provide $4,000 stipends for undergraduate students to conduct summer research on cardiovascular disease.

 

Finally, here at Penn Bioengineering, we are immensely proud to announce that our PhD student Jina Ko was named one of 14 PhD candidates in the inaugural class of Schmidt Science Fellows. Schmidt Fellows are each awarded a $100,000 stipend to cover the cost of living while conducting postdoctoral research. Congratulations, Jina!

Week in BioE (April 24, 2018)

Pushing the Limits of Imaging

7T-MRI
An image showing 7-tesla MRI of the human brain

Since the late 1970s with the advent of computed tomography (CT), medical imaging has grown exponentially. Magnetic resonance imaging (MRI) offers some of the clearest pictures of human anatomy and pathology, particularly as the strength of the magnetic field used (measured in units called Teslas) increases. However, MRI machines are expensive, and the costs increase as one uses a machine with higher field strength to ‘see’ the human more closely. Therefore, it is often more useful (and certainly less expensive) to modify existing MRI technology on hand, rather than acquire a new machine.

A recent example is the work of Tamer Ibrahim, PhD, Associate Professor of Bioengineering at the University of Pittsburgh. Dr. Ibrahim used a series of multiple NIH grants to develop a coil system for Pitt’s 7T-MRI — one of only approximately 60 worldwide — enabling it to more accurately image the brain’s white matter. Dr. Ibrahim is interested in seeing how hyperintensity in the white matter is related to depression, which is one of the highest-burden but least-discussed diseases in the world. Called a “tic-tac-toe” radiofrequency coil setting, the device that Dr. Ibrahim created is a network of antennas fitted to the head that minimize concerns such as coil heating and radiofrequency intensity losses, as well as safety concerns.

Dr. Ibrahim has more NIH funding on the way to continue optimizing his device and apply it in other psychiatric and neurological disorders. Rather than purchasing a new MRI machine with higher field strengths to achieve this image quality, Dr. Ibrahim’s coil design can be used on existing machines. One possible outcome is more clinicians using this new coil to study how changes in the brain’s white matter structure occur in a broad range of brain diseases, leading to both earlier detection anfor ad more effective treatment.

Smart Shunt for Hydrocephalus

Hydrocephalus, once more commonly known as “water on the brain,” is a condition marked by abnormal accumulation of cerebrospinal fluid (CSF) in the skull. If unchecked, the accumulation of fluid will create dangerous pressures in the brain that can result in brain damage. Hydrocephalus occurs in one in every 1,000 births, and nearly 400,000 adults in the US suffered at least on episode of hydrocephalus. For both infants and adults, hydrocephalus is often treated surgically with the installation of a shunt to channel the excess CSF out of the cranium. These shunts are simple but effective devices that operate mechanically. However, since they’re entirely mechanical, they fail over time. Being able to determine that such a failure was imminent could allow patients to receive a replacement shunt before complications arise.

To meet this clinical need, a group of scientists at the University of Southern California (USC)  updated existing shunt systems with microsensing technology, creating a “smart shunt” that can tell clinicians how an installed shunt is functioning and alert the clinician that a replacement is needed. The group, including Ellis Fan-Chuin Meng, PhD, Gabilan Distinguished Professorship in Science and Engineering, Dwight C. and Hildagarde E. Baum Chair, and Professor of Biomedical Engineering and Electrical Engineering-Electrophysics, has created a start-up called Senseer to produce these smart shunts.

The shunt currently measures pressure, flow, and occlusion using miniature microelectronics sensors. If device approval comes, the company hopes to move on to developing smart sensors for other organ systems.

DNA-based Drug Testing

Drug and alcohol testing is a controversial topic, partly because of the balance between individual rights to use legal drugs and potential for societal harm if these drugs are abused or if patients transition into illegal drug use and dependence. Inventing technology to determine when, and how much, a person has been drinking or using drugs (including tobacco) would probably increase, rather than decrease, the controversy involved in the topic.

New technology reported recently adds a new element to this discussion. According to Robert Philibert, MD, PhD, Professor of Psychiatry at the University of Iowa and an adjunct faculty member in the Department of Biomedical Engineering, his company’s tests, which rely on epigenetic markers of substance use, could be used, for example, to inform a primary care physician about the actual history of substance use, rather than relying solely on patients’ self-reported use.

Dr. Philibert’s tests are currently pending approval by the Food and Drug Administration. Marketing for the products will begin in the coming weeks.

People and Places

Recognizing the changing priorities in engineering and the growing role of data sciences, Boston University has decided to adapt its curriculum by adding data science requirements for all majors. According to John White, PhD, Chair of the Department of Biomedical Engineering, “Advances in data sciences and computing technology will allow us to make sense of all these data.”

The Biomedical Science Program at Howard Payne University in Brownwood, Texas, has received a $200,000 grant from  the James A. “Buddy” Davidson Charitable Foundation to endow a scholarship in Davidson’s name, as well as to refurbish the program’s Winebrenner Memorial Hall of Science.

Finally, we offer our congratulations this week to James C. Gee, PhD, Professor of Radiologic Science in Radiology at the University of Pennsylvania’s Perelman School of Medicine and a Graduate Group faculty member in Penn’s Department of Bioengineering.  Dr. Gee was named a fellow of the American Institute for Medical and Biological Engineering.