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 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 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 (July 27, 2017)

The Brain in Focus

BrainAt Caltech, scientists are exploiting the information generated by body movements, determining how the brain codes these movements in the anterior intraparietal cortex — a part of the brain beneath the top of the skull. In a paper published in Neuron, Richard A. Andersen, James G. Boswell Professor of Neuroscience at Caltech, and his team tested how this region coded body side, body part, and cognitive strategy, i.e., intention to move vs. actual movement. They were able determine specific neuron groups activated by different movements. With this knowledge, more effective prosthetics for people experiencing limb paralysis or other kinds of neurodegenerative conditions could benefit enormously.

Elsewhere in brain science, findings of chronic traumatic encephalopathy in football players have raised significant controversy. Seeking to better understand head impact exposure in young football players, scientists from Wake Forest University led by biomedical engineer Joel D. Stitzel, fitted athletes with telemetric devices and collected four years of data and more than 40,000 impacts. They report in the Journal of Neurotrauma that, while all players experienced more high magnitude impacts during games compared to practices, younger football players experienced a greater number of such impacts during practices than the other groups, and older players experienced a greater number during actual games. The authors believe their data could contribute to better decision-making in the prevention of football-related head injuries.

Up in Canada, a pair of McGill University researchers in the Department of Neurology and Neurosurgery — Professor Christopher Pack and Dave Liu, a grad student in Dr. Pack’s lab — found that neuroplasticity might apply to more parts of the brain than previously thought. They report in Neuron that the middle temporal area of the brain, which contributes to motion discrimination and can be inactivated by certain drugs, could become relatively impervious to such inactivation if pretrained. Their findings could have impacts on both prevention of and cures for certain types of brain injury. 

The Virtues of Shellfish

If you’ve ever had a diagnostic test performed at the doctor’s office, you’ve had your specimen submitted to bioassay, a test in which living cells or tissue is used to test the sampled material. University of Washington bioengineer Xiaohu Gao and his colleagues used polydopamine, an enzyme occurring in shellfish, to increase the sensitivity of bioassays by orders of magnitude. As reported in Nature Biomedical Engineering, they tested the technology, called enzyme-accelerated signal enhancement (EASE), in HIV detection, finding that it was able to help bioassays identify the virus in tiny amounts. This advance could lead to earlier diagnosis of HIV, as well as other conditions.

Mussels are also contributing to the development of new bioadhesives. Julie Liu, associate professor of chemical engineering at Purdue, modeled an elastin-like polypeptide after a substance produced naturally by mussels, reporting her findings in Biomaterials. With slight materials, Dr. Liu and her colleagues produced a biomaterial with moderate adhesive strength that demonstrated the greatest strength yet among these materials when tested under water. The authors hope to develop a “smart” underwater adhesive for medical and other applications.

Science in Motion

Discussions of alternative forms of energy have focused on the big picture, such as alleviating our dependence on fossil fuels with renewable forms of energy, like the sun and wind. On a much smaller level, however, engineers are finding smaller energy sources — specifically people.

Reporting in ACS Energy Letters, a research team led by Vanderbilt’s Cary Pint, assistant professor in the Department of Mechanical Engineering and head of Vanderbilt’s Nanomaterials and Energy Devices Laboratory Nanomaterials and Energy Devices Laboratory, designed a battery in the form of an ultrathin black phosphorous device that can generate electricity as it is bent. Dr. Pint describes the device in a video here. Although it can’t yet power an iPhone, the possibility isn’t far away.

Moving Up

Two BE/BME departments have named new chairs. At the University of Utah, David Grainger, who previously chaired the Department of Pharmaceutics and Pharmaceutical Chemistry, will become chair of the Department of Bioengineering. Closer to home, Michael I. Miller became the new chair of the Department of Biomedical Engineering on July 1. Congratulations to them both!

This Week in BioE (June 22, 2017)

Diversifying the Field

One of the ongoing issues in STEM (science, technology, engineering, and medicine) fields is a lack of diversity among students and faculty. Bioengineering stands out among other engineering fields because it enjoys terrific gender diversity. For example, about half of Penn Bioengineers are women, a feature of our class that goes back decades.

diversifyingHowever, diversity extends well beyond gender. For example, the National Research Mentoring Network (NRMN) has been working to increase diversity, including among students with disabilities. A consortium of people and groups providing mentors for science students, the MRMN recently highlighted the American Association for the Advancement of Science’s (AAAS) Entry Point! program, which focuses on helping students with physical disabilities. Mentoring, it turns out is a big part of helping these students succeed.

Another recent development that should help to increase diversity in the field is the awarding of a $1 million grant from the National Science Foundation’s Directorate of Engineering to the University of Wisconsin, Madison, and the College of Menominee Nation (CMN), a native American college in Wisconsin, to collaborate in engineering research and education. The new grant builds on a program begun in 2010 between the colleges to build labs and facilitate the transfer of pre-engineering students from CMN to UWM.

Brain Science Developments

Speaking of education, three recent news stories discuss how we might be able to expedite the learning process, increase intelligence, and reward ourselves when we create art. In one of the stories, a company called Kernel is investing $100 million in research at the University of Southern California to determine whether using brain implants, which have been helpful in some patients with epilepsy, can be used to increase or recover memory. If successful, this may bridge one critical treatment gap in neurology. About one out of every three people with epilepsy don’t respond to drug treatment.

In the second story, scientists at the University of Texas at Dallas were awarded a $5.8 million contract from DARPA to investigate the role of vagus nerve stimulation in accelerated learning of foreign languages. Stimulating the peripheral nervous system to activate and train areas of the brain is one more example that our nervous system is connected in ways that we do not yet understand completely. The Department of Defense hopes to use the technology to more quickly train intelligence operatives and code breakers.

Finally, in a third story involving the brain, a professor at Drexel University used functional near-infrared spectroscopy to determine which parts of the brain were activated while participants were making art. Dr. Girija Kaimal’s team found that creative endeavors activate the brain’s rewards pathway, as well as elevating the participants’ self-opinion. So making art always made people feel good about themselves; now we know more of the reasons why.