Week in BioE (October 6, 2017)

We Bleed Green

field goalBiomechanics is a subdiscipline within bioengineering with many applications that include studying how tissue forms and grows during development (see our profile of incoming faculty member Alex Hughes to learn more) and determining how the ‘imprint’ of spine-based pain can be treated with anti-inflammatory medication (see story here on work from the lab of Dr. Beth Winkelstein). Understanding and analyzing human performance are other areas of biomechanics application. On September 24, Eagles kicker Jake Elliott set a team record when he kicked a 61 yard field goal at the end of regulation time to beat the Giants. Marking the achievement, the Philadelphia Inquirer featured an interview with Dr. Chase Pfeifer, a biomedical engineer from the University of Nebraska-Lincoln (UNL), to find out what factors contribute to a successful field goal from this distance. Pfeifer has both knowledge and experience with this question; he was a backup kicker for the Florida State Seminoles as an undergraduate. In the Inquirer, Dr. Pfeifer explained to readers the biophysics behind Elliott’s record kick.

Dr. Pfeifer assures readers that there’s more to kicking a 61-yard field goal than strong muscles. He explains, “The timing of muscle activation was actually more important than muscle strength in achieving that higher foot velocity.” Four muscle groups were activated by Elliott to set his record. In addition, Pfeifer’s colleague at UNL, Professor Tim Gay of the physics department, explained to the Inquirer how the climatic conditions favored Elliott’s success. Specifically, since it was a hot day, the air was less dense, allowing for longer kick distances.

Speaking of football, a new article in Annals of Biomedical Engineering offers some hope for NFL players and the league itself in the wake of growing awareness and concern about chronic traumatic encephalopathy (CTE). The increased focus on CTE has resulted in increased research on the condition and its prevention. Real-time measurement of impact energy in head injuries has, until now, relied on measurements of the motion of the head or helmet, rather than measuring the impact energy directly.

In the Annals article, scientists from Brigham Young University, including David T. Fullwood, Ph.D., professor of mechanical engineering, report on the testing of a new sensor used to measure the impact event. The authors implanted nano-composite foam (NCF) sensors into football helmets and then submitted the helmets to two dozen drop tests. The data collected from the foam sensors were compared to two of the most widely used indices to measure head injury risk, achieving excellent correlation (>90%) with injury risk indicators. The authors intend to test newer models of the sensors in the future, as well as in vivo testing.

Breast Cancer News

Despite significant advances in diagnosis and treatment, breast cancer remains the most common cancer in women. More than 300,000 women are newly diagnosed in the United States each year. Maximizing the effectiveness of treatment involves early detection of the tumor and its metastasis. Imaging plays a key role in this process. However, early tumors are very small, making their detection quite difficult.

In response to this challenge, Zheng-Rong Lu, Ph.D., the M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve University, has coauthored a paper recently published in Nature Communications showing that a newly developed type of molecule could be used for highly sensitive magnetic resonance imaging (MRI) to detect and stratify early breast tumors.

Dr. Lu and his colleagues engineered molecules called fullerenes, which are hollow, spherical molecules of carbon. The team embedded gadolinium, a rare earth metal that is easily detected with MR imaging, into the fullerene to create metallofullerenes. They tested these metallofullerenes both in vitro and in a mouse model to determine how well they enhanced the ability of MRI to detect tumors. Metallofullerene particles could not only distinguish cancers more effectively on MRI, but they could also distinguish more aggressive tumor types from less aggressive ones. In addition, they found that metallofullerenes rapidly cleared from the body via the kidneys, ensuring that these agents would pose minimal toxicity risk. If this technology proves effective in humans, it could significantly improve the early detection of breast cancer and, in turn, survival rates.

One possible risk for breast cancer patients is the metastasis of the cancer to other body regions.  Scientists at Cornell identified a mineral process underlying breast cancer metastasis to bones, reporting their findings in PNAS. Led by Claudia Fischbach-Teschl, Ph.D., associate professor of biomedical engineering at Cornell, the authors investigated how hydroxylapatite — a naturally occurring mineral — participates in metastasis.

Dr. Fischbach-Teschl and her colleagues used X-ray scattering and Raman spectroscopy to examine the nanostructures of hydroxylapatite in the bones of mice with and without breast cancer. They found that bones were more likely to be metastasized by primary breast tumors if the hydroxylapatite crystals in them were less mature. Before the cancer spreads to the bone, the authors found that the cancer “communicates” with these immature crystals, preparing sites in the bone to which the cancer can spread.

With 80% of metastatic breast cancer cases spreading to the bones, the discovery of the Cornell team could contribute enormously to preventing metastasis — not only of breast cancer but also of any cancer with a greater likelihood of spreading to the bones.

A Review of Glucose Monitoring Technology

Our ability to treat diabetes has consistently improved over the years, but the need for patients with the disease to monitor their blood glucose requires either multiple needle pricks or invasive insulin pumps.  However, several technologies are in development around the world to make blood glucose monitoring less cumbersome. In a new article published in Bioengineering, engineers in the United Arab Emirates offer a review of the latest technologies, including analytic methods that could streamline decisions on doses of insulin to offset high glucose levels.

People and Places

The University of California, Davis, opened its Molecular Prototyping and BioInnovation Laboratory (MPBIL) in 2014. Since then, the “biomaker lab” has stood as an example of the future of biotechnology education. In collaboration with UCD’s First-Year Seminar Program, the MPBIL has launched a student-designed pilot course that has thus far yielded three seminars. You can read more about UCD’s innovative program at their Web site.

To promote diversity in engineering, the cosmetics company L’Oréal started the L’Oréal USA For Women in Science Program, which awards Changing the Face of STEM mentoring grants. Among this year’s recipients is John Hopkins University’s Sridevi Sarma, Ph.D. Dr. Sarma, who is an associate professor of biomedical engineering, will use her grant in collaboration with the Girls Scouts of Central Maryland to promote physics education for young women. Congratulations to her!

Week in BioE (September 29, 2017)

An Immune Cell Atlas

atlas
A human B cell

The human immune system deploys a variety of cells to counteract pathogens when they enter the body. B cells are a type of white blood cell specific to particular pathogens, and they form part of the adaptive immune system. As these cells develop, the cells with the strongest reactions to antigens are favored over others. This process is called clonal selection. Given the sheer number of pathogens out there, the number of different clonal lineages for B cells is estimated to be around 100 billion. A landscape like that can be difficult to navigate without a map.

Luckily, an atlas was recently published in Nature Biotechnology.  It is the work of scientists collaborating between Penn’s own Perelman School of Medicine and faculty from the School of Biomedical Engineering, Science and Health Systems at our next-door neighbor, Drexel University. Using tissue samples from an organ donor network, the authors, led by Nina Luning Prak, MD, PhD, of Penn and Uri Heshberg, Ph.D., of Drexel, submitted the samples to a process called deep immune repertoire profiling to identify unique clones and clonal lineages. In total, they identified nearly a million lineages and mapped them to two networks: one in the gastointestinal tract and one that connects the blood, bone marrow, spleen, and lungs. This discovery suggests that the networks might be less complicated than initially thought. Also, it confirms a key role for the immune system in the gut.

Not only does this B cell atlas provide valuable information to the scientific community, but it also could serve as the basis for immune-based therapies for diseases. If we can identify these lineages and how clonal selection occurs, we could identify the most effective immunological cells and perhaps engineer them in the lab. At the very least, the extent to which scientists understand how B cells are formed and develop has received an enormous push with this research.

Understanding Muscle Movement

Natural movements of limbs require the coordinated activation of several muscle groups. Although the molecular composition of muscle is known, there remains a poor understanding of how these molecules coordinate their actions to confer power, strength, and endurance to muscle tissue. New fields of synthetic biology require this new knowledge to efficiently produce naturally inspired muscle substitutes.

Responding to this challenge, scientists at Carnegie Mellon University, including Philip R. LeDuc, Ph.D.,  William J. Brown Professor of Mechanical Engineering and Professor of Biomedical Engineering, have developed a computational system to better understand how mixtures of specific myosins affect muscle properties. Their method, published in PNAS, uses a computer model to show that mixtures of myosins will unexpectedly produce properties that are not the average of myosin molecular properties. Instead, the myosin mixtures coordinate and complement each other at the molecular level to create emergent behaviors, which lead to a robustness in how the muscle functions across a broad range. Dr. LeDuc and his colleagues then confirmed their model in lab experiments using muscle tissue from chickens. In the future, this new computational method could be used for other types of tissue, and it could prove useful in developing treatments for a variety of disorders.

Determining Brain Connectivity

How the brain forms and keeps memories is one of the greatest challenges in neuroscience. The hippocampus is a brain region considered critical for remembering sequences and events. The connections made by the hippocampus to other brain regions is considered critical for the hippocampus to integrate and remember experiences. However, this broad connectivity of the hippocampus to other brain areas raises a critical question: What connections are essential for rewiring the brain for new memories?

To offer an explanation for this question, a team of scientists in Hong Kong published a paper in PNAS in which they report on a study conducted in rats using resting-state function MRI. The study team, led by Ed X. Wu, Ph.D., of the University of Hong Kong, found that stimulation of a region deep in the hippocampus would propagate more broadly out into many areas of the cortex. The stimulation frequency affected how far this signal propagated from the hippocampus and pointed out the ability for frequency-based information signals to selectively connect the hippocampus to the rest of the brain. Altering the frequency of stimulation could affect visual function, indicating that targeted stimulation of the brain could have widespread functional effects throughout the brain.

Although human and rodent brains are obviously different, these findings from rats offer insights into how brain connectivity emerges in general. Similar studies in humans will be needed to corroborate these findings.

Seeing Inside a Tumor

Years of research have yielded the knowledge that the most effective treatments for cancer are often individualized. Knowing the genetic mutation involved in oncogenesis, for instance, can provide important information about the right drug to treat the tumor. Another important factor to know is the tumor’s chemical makeup, but far less is known about this factor due to the limitations of imaging.

However, a new study published in Nature Communications is offering some hope in this regard. In the study, scientists led by Xueding Wang, Ph.D., associate professor of biomedical engineering and radiology at the University of Michigan, used pH-sensing nanoprobes and multiwavelength photoacoustic imaging to determine tumor types in phantoms and animals. This new technology is based on the principle that cancerous cells frequently lower the pH levels in tissue, and designing probes with properties that are pH sensitive provides a method to find tumors with imaging methods and also treat these tumors.

With this technology, Dr. Wang and his colleagues were able to obtain three-dimensional images of pH levels inside of tumors. Importantly, it allowed them to noninvasively view the changes in a dye injected inside the tumor. Although a clinical application is years away, the information obtained using the Michigan team’s techniques could add significantly to our knowledge about tumorigenesis and tumor growth.

The Role of Bacteria in MS

The growing awareness of how bacteria interact with humans to affect health has led to the emergence of new scientific areas (e.g., human microbiome). Research findings from scientists collaborating between Caltech and UCSF suggest bacteria can play a role in the onset of multiple sclerosis. These investigators include Sarkis K. Mazmanian, Ph.D., Luis B. and Nelly Soux Professor of Microbiology and a faculty member in the Division of Biology and Biological Engineering at Caltech. Reporting their research results in PNAS, the researchers found several bacteria elevated in the MS microbiome. Study results showed that these bacteria regulated adaptive immune responses and helped to create a proinflammatory milieu. The identification of the bacteria interacting with immunity in MS patients could result in better diagnosis and treatment of this disabling disease.

People and Places

Faculty members at the University of California, Irvine, including biomedical engineer Zoran Nenadic, Ph.D., have received an $8 million grant to develop a brain-computer interface. The research using this grant aims to restore function in people with spinal cord injuries. Also, at the University of Texas, Austin, the lab of Amy Brock, Ph.D., an assistant professor in the Department of Biomedical Engineering, has received a three-year $180,000 R21 grant from the National Cancer Institute to develop a barcoding platform to isolate cancer cell lineages and to identify genetic targets for treatment.

Week in BioE (September 22, 2017)

Live Bone Cells Grown in Lab

osteogenesis
An osteoclast, one type of bone cell.

Bone injuries and bone loss can constitute major challenges for patients and the people who treat them. Beyond the need for bone grafts or artificial implants in cases such as severe fractures, cancers metastasizing to the bones can be disabling and disfiguring. Doctors are able to use autologous bone grafts, in which patients are their own bone donors and provides grafts from other bones in their bodies. However, the grafting process compromises the bone from the donor site. In addition, there are specific problems in cases of long bones, such as those in the arms and legs. With these bones, no site of the body can provide sufficient material without becoming severely compromised itself due to bone loss.

Stem cells have been intensively investigated as a source of bone grafts. With their ability to produce a variety of cell lines from the same source, these cells have the potential to be used in a variety of clinical situations. The mechanisms underlying the determination of the type of cell that an individual stem cell will become are known. However, the ability to produce living bone cells in the laboratory had remained elusive – until now.  In an article published online last week by Nature Biomedical Engineering, a group of scientists led in part by Professor Matthew Dalby, a cellular engineer with the Institute of Molecular, Cell and Systems Biology at the University of Glasgow, United Kingdom, reported its success.

Professor Dalby’s tissue engineering team used a nanoscale bioreactor to stimulate mesenchymal stem cells into osteogenesis (bone creation). The bioreactor applied vibrations on a microscopic scale of 1,000 hertz with 15 nanometers of vertical displacement. In their previous work, Professor Dalby and his colleagues could generate only one bone cell sample at a time. In the current paper, they showed the ability to generate multiple cells for three-dimensional tissue. In addition, they showed that the cells could be generated in environments with less rigidity than that in which osteogenesis normally occurs. This is an important advance because the body provides optimal conditions of stiffness for this process, but the lab does not. Should the techniques in the paper prove viable on a greater scale, they could revolutionize the field of bone grafting.

Microfluidics in the News

Since their introduction, organs on a chip (OOCs) have proliferated in the field of bioengineering. These chips use microfluidics technology to create a model of an organ system in the body. However, until now, OOCs have not been used to model the human placenta – the tissue that connects the embryonic sac to the uterine wall during pregnancy.

Responding to the lack of a OOC model of the placenta, two professors at Florida International University (FAU) have developed a placenta OOC. Sarah E. Du, Ph.D., assistant professor of ocean and mechanical engineering, and Andrew Oleinkov, Ph.D., associate professor of biomedical science, have collaborated to create this chip, which they to intend to use to determine the effects of malaria on the placental microenvironment. A $400,000 grant from the NIH will certainly help.

With malaria causing more than 200,000 perinatal deaths annually, beyond the burden we cited last week, there is an urgent need to determine the exact effects of this parasitic infection on the placenta. Without this knowledge, the development of technologies to mitigate or even prevent these effects will be much more difficult. In addition, because of the obvious ethical constraints on prospective testing in natural history studies, the placenta OOC offers an ideal model.

Elsewhere in the field of microfluidics, an NIH grant to scientists at the University of Illinois, Urbana-Champaign, has gone toward the development of a new test chip to detect sepsis, a condition in which the body’s reaction to infection results in inflammation of the blood vessels and which can cause lethal shock unless detected and treated promptly. The UIUC team developing this more rapid diagnostic technology is led by Rashid Bashir, Ph.D., professor of bioengineering and associate dean of UIUC’s Carle Illinois College of Medicine. Dr. Bashir was lead author on a paper published over the summer in Nature Communications.

Among the more remarkable aspects of the chip developed by Professor Bashir and his colleagues is that it can diagnose sepsis with a single drop of blood. Therefore, in addition to the device’s portability and size, which allows it to be used at the point of care, it is only necessary to use 10 microliters of blood to complete the test. Other available lab tests for sepsis can require as much as 300 times as much blood. Testing its device against the gold standard of flow cytometry, the UIUC team found that the findings obtained with its biochip were strongly correlated with those from flow cytometry. Unlike the new chip, flow cytometry cannot be performed outside the lab.

Since a large proportion of sepsis patients are treated in intensive care units, the ICU is a likely setting in which the biochip could be used, particularly because some ICUs might be in hospitals where the staff does not have 24-hour lab access. The ability to use this chip at the bedside immediately, rather than waiting until the next morning or longer, could make a key difference in detecting and treating sepsis.

Brains on the Internet

For years, Ray Kurzweil, the computer scientist turned author and inventor, has been discussing a future in which, he claims, the distinction between human and artificial intelligence will disappear. For example, Kurweil imagines brains being uploaded to computers. While what Kurzeil imagines has yet to materialize, scientists in South Africa have created the “Brainternet,” which streams brain waves onto the Internet in real time.

As a student project at the School of Electrical and Information Engineering of the University of Witerstand in Johannesburg led by Adam Pantanowitz, a lecturer in the school, the Brainternet was developed from pre-existing technology. The project starts with portable electroencephalography (EEG), which is worn by the subject and which transmits its signal by telemetry to a Raspberry Pi computer. Then, using open source software, the computer live streams the data to an application programming interface, which in turn allows the data to be published at a website accessible to others.

Beyond being an innovative use of these technologies, the Brainternet could be used in telemedicine applications. For instance, it could be helpful in situations where a specialist neurologist is not in the immediate geographic vicinity. Moreover, for research projects involving EEG measurement during tasks or under certain types of external stimulation, the Brainternet could allow for a much larger sample size to be enrolled, owing to its portability and use of the Internet.

People and Places

Dawn Elliott, Ph.D., chair of the Department of Biomedical Engineering at the University of Delaware, has been elected president of the Biomedical Engineering Society (BMES), for which she had served as treasurer. Dr. Elliott’s term as president will begin in October 2018 and last for two years. As president, she plans to take a closer look at education in the field to determine how bioengineering and biomedical engineering departments can graduate the most successful students. We wish her the best of luck and hearty congratulations.

Week in BioE (September 15, 2017)

A Closer Look

7T-MRI
Seven-tesla MRI of the porcine mitral valve showing the papillary muscle (PM) and chordae tendinae (CT).

Since its invention in the early 1970s, magnetic resonance imaging (MRI) has played an increasingly important role in the diagnosis of illness. In addition, over time, the technology of MRI has evolved enormously, with the ability to render more detailed three-dimensional images using stronger magnetic fields . However, imaging tissues under mechanical loads (e.g., beating heart, lung breathing) are still difficult to image precisely with MRI.

A new study in PLOS One, led by Morten Jensen, Ph.D., of the University of Arkansas, breaks an important technical barrier in high resolution imaging for tissues under mechanical load. Using 3D-printed mounting hardware and 7-tesla MRI, this group produced some of the highest quality images yet produced of the mitral valve exposed to physiological pressures (see above). In the longer term, this method could point to new corrective surgical procedures that would greatly improve the repair procedures for mitral valves.

Oncology Breakthroughs

Among the most significant challenges faced by surgical oncologists is developing a ‘clear margin,’ meaning that the tissue remaining after tumor excision is free of any tumor cells. If the margins are not free of tumor cells, the cancer is more likely to recur. However, until now, it has been impossible to determine if cancer cells were still present in tissue margins before finishing surgery because of the time required to test specimens.

At the University of Texas, Austin, however, scientists are getting closer to overcoming this obstacle. In a recent study published in Science Translational Medicine, this team of scientists presents the MasSpecPen — short for mass spectrometry pen. This device is capable of injecting a tiny drop of water into tissue, extracting the water after it mixes with the tissue, and quickly analyzing the sample’s molecular components. The authors, who included biomedical engineering faculty member Thomas E. Milner, Ph.D., tested the device using ex vivo samples from 253 patients with different varieties of cancer, including breast, lung, and thyroid cancers. The MasSpecPen provided sensitivity, specificity, and accuracy exceeding 96% in all cases. Although it has yet to be tested intraoperatively, if effective under those conditions, the device could become an essential part of the surgeon’s arsenal.

If the MasSpecPen could render surgical treatment of cancer more effective, a device developed at SUNY Buffalo could help doctors diagnose lung cancer earlier. Lung cancer is a particularly deadly variety of cancer because patients don’t feel any discomfort until the cancer has spread to other areas of the body. In collaboration with Buffalo’s Roswell Park Center Institute, microchip manufacturer Intel, and local startup Garwood Medical Devices, a team of scientists, including Professor Edward P. Furlani, Ph.D., from Buffalo’s Department of Chemical and Biomedical Engineering, was awarded a grant from the National Science Foundation to develop a subcutaneous implant incorporating a nanoplasmonic biochip to detect biomarkers of lung cancer. A wearable smart band would receive data from the biochip and would act as an early warning system for lung cancer. The biomarkers selected for the biochip would optimally predict lung cancer risk much earlier than the metastasis stage. If the system that the team develops is successful in diagnosing lung cancer before it spreads, it could greatly improve survival and cure rates.

Feverish Growth

Worldwide but particularly in the Global South, malaria remains a major public health concern. According to a Global Burden of Disease study in 2015, there were nearly 300 million cases of the disease in a single year, with 731,000 fatalities. One of the earliest treatments to combat malaria was invented by British colonialists, who added quinine to the tonic used in the gin and tonic cocktail. More recently the drug artemisinin was developed for fighting malaria. However, this drug and its derivatives are very expensive. The primary reason for this cost is that the drug is extracted from the sweet wormwood plant, which is in short supply. In hopes of producing a greater supply of artemisinin, scientists collaborating among Denmark, Malaysia, and the Netherlands report in Frontiers in Bioengineering and Biotechnology that transplanting the genes responsible for producing atremisinin into Physcomitrella patens, a common moss, led to a much faster production rate of the drug than what is possible with the wormwood plant. The process proved simpler and less expensive than earlier attempts to transplant genes into tobacco plants. If this potential is harnessed correctly, it could make an enormous difference in lessening the global burden of malaria. 

Understanding Fear

We’ve known for years about the flight-or-fight response — the adrenergic response of our bodies to danger, which we share in common with a number of other animals. Once the decision to flee is made, however, we know far less about what determines the escape strategy used. According to Malcolm A. MacIver, professor of biomedical engineering and mechanical engineering in Northwestern University’s McCormick School of Engineering, part of the escape strategy depends on how far away the attacker is. In a paper he coauthored that was published in Current Biology, Dr. MacIver studied threat responses in larval zebrafish and found that a fast-looming stimulus produced either freezing or escape at a shorter interval following the threat perception; when the perceived threat was slow looming, longer latency following the perception of the threat was seen, resulting in a greater variety of types of escape behaviors. While it might seem a giant leap between observing behaviors in fish and higher life forms, the basic mechanism in the “oldest” parts of the brain, from an evolutionary standpoint, are less different than we might think.

People and Places

The University of Maryland has announced that construction on a new building to serve as the home of its Department of Bioengineering will be finished by the end of September. The building is to be named A. James Clark Hall, after a builder, philanthropist, and alumnus of Maryland’s School of Engineering. Further south, George Mason  University in Fairfax, Va., has announced that the new chair of its Department of Engineering there will be Michael Buschmann, Ph.D., an alumnus of MIT and faculty member since the 1990s at École Polytechnique in Montreal. Congratulations, Dr. Buschmann!

 

Week in BioE (September 8, 2017)

A Breath of Fresh Air

lung grafts
A macrophage in the alveolus of a lung.

At Columbia, a new way of treating lung disease is under development. As reported recently in Science Advances, a Columbia research group, headed by Gordana Vunjak-Novakovic, Ph.D., from the Department of Biomedical Engineering, developed a way to prepare grafted lung tissue for transplantation that could make the process easier. The challenge has been removing the epithelial cells, which ultimately make up the surface of the organ, from potential grafts without damaging the blood vessels. Applying a detergent solution to lung tissue from rats, Dr. Vunjak-Novakovic’s team was able to obtain grafts that could subsequently be used as scaffolds for human pulmonary cells and stem cell-derived lung epithelial cells.  Although this approach remains in a very early state, the results here indicate promise for this technology for end-stage lung diseases such as emphysema.

Eliminating Obesity and Diabetes With Injections

You’ve probably heard that there’s an epidemic of obesity in the United States. Obesity carries an enormous health cost because it is linked to a variety of major health complications, including diabetes and heart disease. At a cell level, white fat cells require more energy to work off than brown fat cells. Approaches to fight obesity now include efforts to increase the number of brown fat cells. Scientists at Purdue University might have found a significant shortcut to creating more brown fat cells. By inhibiting the Notch signaling pathway, Meng Deng, Ph.D., of the Weldon School of Biomedical Engineering and his colleagues were able to cause white fat cells to convert into brown cells. Reporting their results in Molecular Therapy, the team used nanoparticles loaded with dibenazapine, a chemical used widely in pharmacology, to treat obese mice with targeted injections of the drug-laden nanoparticles. Results showed that the reduction of white fat in the mice was correlated with improved glucose metabolism and reduced body weight. While it’s not yet time to cancel the gym membership, an easier way to combat obesity could be on the horizon.

Diabetes is a chronic health condition with treatments that include diet management and/or insulin injections. In a new twist on diabetes treatments, scientists at the University of Toronto have shown, in a recent PNAS study, that pancreatic islets cells, which produce insulin, could be injected subcutaneously to reverse diabetes in mice. While the idea of transplanting islets into the pancreas has been investigated for some time, this is the first time that transplants were placed under the skin, far away from the pancreas. Impressively, the modules could be retrieved and reused. If future investigations are successful, these modules could form the basis of a treatment for type 1 (so-called juvenile) diabetes, which is caused by autoimmune destruction of the pancreatic islets.

News from New England

Feng Zhang, Ph.D., associate professor in the Departments of Brain and Cognitive Sciences and of Biological Engineering at MIT, is one of five scientists to receive the Albany Medical Prize in Medicine and Biomedical Research for his work on CRISPR-Cas9 gene editing technology. We offer Dr. Zhang our heartfelt congratulations.

Across the river from Cambridge in Medford, Tufts University has announced that its newly completed Science and Engineering Complex (SEC) will open this semester and will combine classrooms and laboratories — specifically what the developers are calling “lab neighborhoods,” or spaces for collaboration among laboratories working on related research questions. Bruce Panilaitis, Ph.D., a research assistant professor in the Department of Biomedical Engineering, is the director of the SEC, and his department will also have offices there.

Week in BioE (September 1, 2017)

Overcoming CP With Robotics

robotic exoskeletonCerebral palsy (CP) remains one of the most common congenital birth defects, affecting 500,000 American newborns per year. Gait disorders from CP are common, and crouch gait — characterized by misdirection and improper bending of the feet, causing excessive knee bending and the appearance of crouching — is among the most difficult to correct.

Researchers at Northern Arizona University recently developed a new exoskeleton to treat crouch gait. In an article published in Science Translational Medicine, Zach Lerner, Ph.D., assistant professor of mechanical engineering and a faculty member with NAU’s Center for Bioengineering Innovation, tested a robotic, motorized exoskeleton in seven patients with crouch gait. Six of the seven participants using the exoskeleton show improvements on par with surgical procedures to correct crouch gait. Although commercial availability of the exoskeleton will require testing in much larger patient groups, the device is an encouraging development in the treatment of a difficult disorder.

Brain Science News

A couple of weeks ago, we discussed here how the Department of Defense supports research using electrical stimulation of the scalp to direct brain activity. At the University of Texas at Arlington (UTA), bioengineering professor Hanli Liu, Ph.D., received a NIH grant to test how infrared light, rather than electrical stimulation, can achieve similar effects on the brain. In collaboration with two other UTA professors, Professor Liu uses Transcranial Infrafred Brain Stimulation (TIBS) to project infrared light onto the forehead to enhance blood flow and oxygen supply to the underlying area of the brain. With the grant, she and her colleagues intend to develop imaging tools that will provide greater insight into how both TIBS and the brain itself work.

Even as we learn more about the brain, the devastating effects of neurodegenerative diseases show us how much we still don’t know. Certain drugs can slow the inevitable advance of the disease, but beginning treatment early is important to maintaining a sense of normalcy. At Case Western Reserve University, Anant Madabhushi, Ph.D., professor of biomedical engineering, is developing computer technology to distinguish Alzheimer’s from other disorders and to predict onset earlier and more accurately.  Reporting their outcomes in Scientific Reports from testing in nearly 150 patients, Dr. Madabhushi and his colleagues used a variety of clinical measures (blood biomarkers, imaging data, neuropsychological testing) instead of a single test and developed a much more accurate test for detecting Alzheimer’s disease. Their approach, called cascaded multiview canonical correlation (CaMCCo), used the ordered analysis of different tests to stratify different patient groups at each stage, rather than developing a single combined measure all at once. More work will be needed to determine how this approach can lead to earlier detection of Alzheimer’s, but its accuracy is very encouraging for future studies.

Causes for Congratulations

Rose-Hulman Institute of Technology has announced that Kay C. Dee, Ph.D., is among the recipients of this year’s Inspiring Leaders in STEM Award from Insight Into Diversity magazine.  Professor Dee, Associate Dean of Learning and Technology and Professor of Biology and Biomedical Engineering at Rose-Hulman, is the former head of her department. As a dean, she has focused on several issues, including easier access for students with disabilities. Congratulations to Dr. Dee!

Also, several bioengineering and biomedical engineering departments across the country are celebrating birthdays. The departments at both the University of Virginia (biomedical engineering) and the University of Michigan (bioengineering) are 50 years old, with Michigan also celebrating the 20th birthday of their biomedical engineering department. The comparative baby of the group, the Department of Biomedical Engineering at Tulane University, turns 40. Happy birthday all! 

Week in BioE (August 25, 2017)

Beyond Sunscreen

skin cancer
The sun

Excessive exposure to the sun remains a leading cause of skin cancers. The common methods of protection, including sunscreens and clothing, are the main ways in which people practice prevention. Amazingly, new research shows that what we eat could affect our cancer risk from sun exposure as well.  Joseph S. Takahashi, Ph.D., who is chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, was one of a team of scientists who recently published a paper in Cell Reports that found that by restricting the times when animals ate, their relative risk from exposure to ultraviolet light could change dramatically.

We tend to think of circadian rhythms as being among the reasons why we get sleepy at night, but the skin has a circadian clock as well, and this clock regulates the expression of certain genes by the epidermis, the visible outermost layer of the skin. The Cell Reports study found that food intake also affected these changes in gene expression. Restricting the eating to time windows throughout a 24h cycle, rather than providing food all the time, led to reduced levels of a skin enzyme that repairs damaged DNA — the underlying cause of sun-induced skin cancer. The study was conducted in mice, so no firm conclusions about the effects in humans can be drawn yet, but avoiding midnight snacks could be beneficial to more than your weight.

Let’s Get Small

Nanotechnology is one of the most common buzzwords nowadays in engineering, and the possible applications in health are enormous. For example, using tiny particles to interfere with the cancer signaling could give us a tool to stop cancer progression far earlier than what is possible today. One of the most recent approaches is the use of star-shaped gold particles — gold nanostars — in combination with an antibody-based therapy to treat cancer.

The study authors, led by Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering at Duke, combined the gold nanostars with anti-PD-L1 antibodies. The antibodies target a protein that is expressed in a variety of cancer types. Focusing a laser on the gold nanostars heats up the particles, destroying the cancer cells bound to the nanoparticles. Unlike past nanoparticle designs, the star shape concentrate the energy from the laser at their tips, thus requiring less exposure to the laser. Studies using the nanostar technology in mice showed a significant improvement in the cure rate from primary and metastatic tumors, and a resistance to cancer when it was reintroduced months later.

Nanotechnology is not the only new frontier for cancer therapies. One very interesting area is using plant viruses as a platform to attack cancers. Plant viruses stimulate a natural response to fight tumor progression, and these are viewed by some as ‘nature’s nanoparticles’. The viruses are complex structures, and offer the possibility of genetic manipulation to make them even more effective in the future. At Case Western Reserve University, scientists led by Nicole Steinmetz, Ph.D., associate professor of biomedical engineering, used a virus that normally affects potatoes to deliver cancer drugs in mice. Reporting their findings in Nano Letters, the authors used potato virus X (PVX) to form nanoparticles that they injected into the tumors of mice with melanoma, alongside a widely used chemotherapy drug, doxorubicin. Tumor progression was halted. Most importantly, the co-administration of drug and virus was more effective than packing the drug in the virus before injection.  This co-administration approach is different than past studies that focus on packaging the drug into the nanoparticle first, and represents an important shift in the field.

Educating Engineers “Humanely”

Engineering curricula are nothing if not rigorous, and that level of rigor doesn’t leave much room for education in the humanities and social sciences. However, at Wake Forest University, an initiative led by founding dean of engineering Olga Pierrakos, Ph.D., will have 50 undergraduate engineering students enrolled in a new program at the college’s Downtown campus in Winston-Salem, N.C. The new curriculum plans for an equal distribution of general education/free electives relative to engineering coursework, with the expectation that the expansion of the liberal arts into and engineering degree will develop students with a broader perspective on how engineering can shape society.

People in the News

At the University of Illinois, Urbana-Champaign, Rashid Bashir, Ph.D., Grainger Distinguished Chair in Engineering and professor in the Department of Bioengineering, has been elevated to the position of executive associate dean and chief diversity officer at UIUC’s new Carle Illinois College of Medicine. The position began last week. Professor Michael Insana, Ph.D., replaces Dr. Bashir as department chair.

At the University of Virginia, Jeffrey W. Holmes, Ph.D., professor of biomedical engineering and medicine, will serve as the director of a new Center for Engineering in Medicine (CEM). The center is to be built using $10 million in funding over the next five years. The goal of the center is to increase the collaborations among engineers, physicians, nursing professionals, and biomedical scientists.

Week in BioE (August 18, 2017)

SynBio
An embryonic stem cell

SynBio News

Synthetic biology (SynBio) is an important field within bioengineering. Now, SynBio and its relationships with nanotechnology and microbiology will get a big boost with a $6 million grant from the National Science Foundation awarded to the lab of Jason Gleghorn, Ph.D., assistant professor of biomedical engineering at the University of Delaware. The grant, which comes from the NSF’s Established Program to Stimulate Competitive Research, will fund research to determine the interactions between a single virus and single microbe, using microfluidics technology so that the lab staff can examine the interactions in tiny droplets of fluid, rather than using pipettes and test tubes. They believe their research could impact healthcare broadly, as well as perhaps help agriculture by increasing crop yields.

While must SynBio research is medical, the technology is now also being used in making commercial products that will compete with other natural or chemically synthesized products. Antony Evans’s company Taxa Biotechnologies has developed a fragrant moss that he hopes can compete against the sprays and other chemicals you see on the store shelves. Using SynBio principles, Taxa isolates the gene in plants causing odor and transplants these genes to a simple moss in a glass terrarium that, with sufficient sunlight, water, carbon dioxide, will provide one of three scents completely naturally. Technically, the mosses are genetically modified organisms (GMOs), but since people aren’t eating them, they aren’t likely to generate the controversy raised by GMO foods. Taxa has also been working on transplanting bioluminescence genes to plants to provide light without requiring electricity, all as a part of a larger green campaign.

A Few Good Brains

A division of the U.S. Department of Defense, the Targeted Neuroplasticity Training (TNT) program of the Defense Advanced Research Projects Agency (DARPA) will fund the research of Stephen Helms Tillery, Ph.D., of the School of Biological & Health Systems Engineering at Arizona State University, who is investigating methods of enhancing cognitive performance using external stimulation. The ASU project is using transdermal electrical neuromodulation to apply electrical stimulation via electrodes placed on the scalp to determine the effects on awareness and concentration. DARPA hopes to obtain insight into how to improve decision making among troops who are actively deployed. The high-stress environment of a military deployment, combined with the fact that soldiers tend to get suboptimal amounts of sleep, leaves them with fatigue that can cloud judgment in moments of life or death. If the DARPA can find a way to alleviate that fatigue and clarify decision-making processes, it would likely save lives.

Circulatory Science

End-stage organ failure can be treated by transplantation, but waiting lists are long and the number of donors still insufficient, so alternatives are continually sought. In the field of regenerative medicine, which is partly dedicated to finding alternatives, scientists at Ohio State have developed a technology called tissue nanotransfection, which can generate any cell type within a patient’s own body. In a paper published in Nature Nanotechnology, professors Chandan Sen and James Lee and their research team describe how they used nanochip technology to reprogram skin cells into vascular cells. After injecting these cells into the injured legs and brains of mice and pigs, they found the cells could help to restore blood flow. The applications to organ systems is potentially limitless.

For cardiac patients whose conditions can be treated without need for a transplant, who make up the vast majority of this cohort,  stents and valve prostheses are crucial tools. However, these devices and the procedures to implant them have high complication rates. Currently, patients receiving prosthetic valves made in part of metal must take blood thinners to prevent clots, and these drugs can greatly diminish quality of life and limit activity, particularly in younger patients. At Cornell, Jonathan Butcher, Ph.D., associate professor of biomedical engineering, is developing a prosthetic heart valve with small niches in the material loaded with biomaterials to maintain normal heart function and prevent clotting. While it has been possible for some time to coat the surface of an implant with a drug or chemical to facilitate its integration and function, these niches allow for a larger depot of such a material to be distributed over a longer period of time, increasing the durability of the positive effects of these procedures.

Smartphone Spectrometry

A number of medical diagnoses are accomplished by testing of bodily fluids, and spectrometry is a key technology in this process. However, spectrometers are expensive and usually not very portable, posing a challenge for health professionals working outside of traditional care settings. Now, a team led by Brian Cunningham, Ph.D., from the University of Illinois, Urbana-Champaign, has published in Lab on a Chip a paper detailing their creation of a smartphone-integrated spectroscope. Called the spectral Transmission-Reflectance-Intensity (TRI)-Analyzer, it uses microfluidics technology to provide point-of-care analysis to facilitate treatment decisions. The authors liken it to a Swiss army knife in terms of versatility and stress that the TRI Analyzer is less a specialized device than a mobile laboratory. The device costs $550, which is several times less than common lab-based instruments.

New Chair at Stanford

Stanford’s Department of Bioengineering has announced that Jennifer Cochran, Ph.D., will begin a five-year term as department chair beginning on September 1. Dr. Cochran arrived at Stanford in 2005 after earning degrees at the University of Delaware and MIT. Cochran has two connections to Penn – she is currently serving as a member of our department advisory board and completed her postdoctoral training in Penn Medicine. Our heartiest congratulations to her!

Week in BioE (August 10, 2017)

Preventing Transplant Rejection

rejection
A healthy human T cell, one of the key immune system cells.

Organ transplantation is a lifesaving measure for people with diseases of the heart, lungs, liver, and kidneys that can no longer be treated medically or surgically. The United Network for Organ Sharing, a major advocacy group for transplant recipients, reports that a new person is added to a transplant list somewhere in America every 10 minutes. However, rejection of the donor organ by the recipient’s immune system remains a major hurdle for making every transplant procedure successful. Unfortunately, the drugs required to prevent rejection have serious side effects.

To address this problem, a research team at Cornell combined DNA sequencing and informatics algorithms to identify rejection earlier in the process, making earlier intervention more likely. The team, led by Iwijn De Vlaminck of the Department of Biomedical Engineering, report in PLOS Computational Biology that a computer algorithm they developed to detect donor-derived cell-free DNA, a type of DNA shed by dead cells, in the blood of the recipient could predict heart and lung allograft rejection with a 99% correlation with the current gold standard. The earlier that signs of rejection are detected, the more likely it is that an intervention can be performed to save the organ and, more importantly, the patient.

Meanwhile, at Yale, scientists have used nanoparticles to fight transplant rejection. Publishing their findings in Nature Communications, the study authors, led by Jordan S. Pober, Bayer Professor of Translational Medicine at Yale, and Mark Saltzman, Goizueta Foundation Professor of Chemical and Biomedical Engineering, used small-interfering RNA (siRNA) to “hide” donated tissue from the immune system of the recipient. Although the ability of siRNA to hide tissue in this manner has been known for some time, the effect did not last long in the body. The Yale team used poly(amine-co-ester) nanoparticles to deliver the siRNA that extended and extended its duration of effect, in addition to developing methods to deliver to siRNA to the tissue before transplantation. The technology has yet to be tested in humans, but provides an exciting new approach to help solve the transplant rejection challenge in medicine.

Africa in Focus

A group of engineering students at Wright State University, led by Thomas N. Hangartner, professor emeritus of biomedical engineering, medicine and physics, traveled to Malawi, a small nation in southern Africa, to build a digital X-ray system at Ludzi Community Hospital. Once on site, Hangartner and his student team trained the staff to use system on patients. The group hopes they have made a significant contribution to improving the standard of care in the country, which currently allocates only 9% of its annual budget to healthcare. While the project admitted has limited impact, it’s important to bear in mind that expanding public health on a global level is a game of inches. The developing world will rise to the standards of the developed world one village at a time, one hospital at a time.

Speaking of Africa, the recent Ebola outbreak in West Africa had global implications and prompted many international organizations to identify better methods to identify early signs of outbreak. Since diseases like Ebola can spread rapidly and aggressively, detecting the outbreak early can save thousands of lives. To this end, Tony Hu of Arizona State University’s School of Biological and Health Systems Engineering has partnered with the U.S. Army to develop a platform using porous silicone nanodisks that, coupled with a mass spectrometer, could be used to detect Ebola more quickly and less expensively. In particular, by determining the strain of the Ebola virus detected, treatment could be more specifically individualized for the patient. Dr. Hu presents the technology in a video available here.

Neurotech News

Karen Moxon, professor of biomedical and mechanical engineering at the University of California, Davis, recently showed that rats with spinal injuries recovered to a more significant extent when treated with a combination of serotonergic drugs and physical therapy. Dr. Moxon found that the treatment resulted in cortical reorganization to bypass the injury. Many consider combining two different drugs to treat a disease or injury; Moxon’s clever approach used a drug in combination with the activation of cortical circuits (electroceuticals), and approach that was not considered possible with some types of spinal cord injuries.

At Stanford,  Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, led a study team that recently reported in Science Translational Medicine that mice bred to have a type of autism could receive a genetic therapy that caused their brain cells to activate differently. Although the brains of the autistic mice were technically normal, the mice were unsocial and lacked curiosity. Treatment modulated expression of the CNTNAP2 gene, resulting in increased sociability and curiosity. Their findings could have tremendous implications for treating autism in humans.

Elsewhere in neurotech, Cornell announced its intention to create a neurotech research hub, using a $9 million grant from the National Science Foundation. Specializing in types of neurological imaging, the new NeuroNex Hub and Laboratory for Innovative Neurotechnology will augment the neurotech program founded at Cornell in 2015.

Academic Developments

Two important B(M)E department have developed new programs. In Montreal, McGill University has introduced a graduate certificate program in translational biomedical engineering (video here). Also at the annual meeting of the American Society for Engineering Education in Columbus, Ohio, an interdisciplinary group of scholars from Worcester Polytechnic Institute, including three professors of engineering, presented a paper entitled “The Theatre of Humanitarian Engineering.” The authors developed an experimental role-playing course in which the students developed a waste management solution for a city. According to the paper’s abstract, a core misunderstanding about engineering is the belief that it exists separately from social and political contexts. With the approach they detail, the authors believe they could address the largely unmet call for greater integration of engineering with the humanities and social sciences on the academic level.

Week in BioE (August 3, 2017)

There’s news in bioengineering every week, to be sure, but the big story this past week is one that’s sure to continue appearing in headlines for days, weeks, and months — if not years — to come. This story is CRISPR-Cas9, or CRISPR for short, the gene-editing technology that many geneticists are viewing as the wave of the future in terms of the diagnosis and treatment of genetic disorders.

Standing for clustered regularly interspaced short palindromic repeats, CRISPR offers the ability to cut a cell’s genome at a predetermined location and remove and replace genes at this location. As a result, if the location is one at which the genes code for a particular disease, these genes can be edited out and replaced with healthy ones. Obviously, the implCRISPRications for this technology are enormous.

This week, it was reported that, for the first time, CRISPR was successfully used by scientists to edit the genomes of human embryos. As detailed in a paper published in Nature, these scientists edited the genomes of 50 single-cell embryos, which were subsequently allowed to undergo division until the three-day mark, at which point the multiple cells in the embryos were assessed to see whether the edits had been replicated in the new cells.  In 72% of them, they had been.

In this particular case, the gene edited out was one for a type of congenital heart defect, and the embryos were created from the eggs of healthy women and the sperm of men carrying the gene for the defect. However, the experiments prove that the technology could now be applied in other disorders.

Needless to say, the coverage of this science story has been enormous, so here is a collection of links to coverage on the topic. Enjoy!