Week in BioE (October 20, 2017)

spina bifida
Computed tomography showing spina bifida occulta (arrow).

Fetal Repair Without Surgery?

Spina bifida is a fairly common type of birth defect caused by incomplete closure of the backbone and tissue surrounding the spinal cord. Fetal surgery can repair the defect before delivery, but this invasive surgery can lead to high risk preterm delivery.

A new material may dramatically reduce the invasiveness of surgery needed to correct spina bifida. In a new article in Macromolecular Bioscience, surgeons and bioengineers from the University of Colorado report on one of these alternatives. One of the lead authors was Daewon Park, Ph.D., assistant professor of bioengineering. Dr. Park and his colleagues developed a reverse thermal gel, which is an injectable liquid that forms a gel at higher temperatures when injected into the body. Ultimately a gel like this one could be injected at or near the spine, where it would cover the defect in a spina bifida patient, harden into a gel, and ultimately repair the defect by deploying stem cells or engineered tissue.

The research team’s most recent study indicates that their gel retained its stability in amniotic fluid and was compatible with neural tube cells. They also tested the gel in two animal models, with successful results. The gel is still far from being used in actual fetal surgery cases, but the authors will continue to test the gel under conditions increasingly similar to the human amniotic sac.

Building Better Brains

UCLA scientists have developed an improved system for generating brain structures from stem cells. The team of scientists, led by Bennett G. Novitch, Ph.D., professor of neurobiology at UCLA, report their findings in Cell Reports.  Importantly, the methods used by Dr. Novitch and his colleagues fine-tuned and simplified earlier efforts in this area, developing a method that did not require any specific reactors to generate the tissue. They were also able to generate tissue resembling the basal ganglia for the first time, indicating promise for using these tissues to model diseases affecting that part of the brain, including Parkinson’s disease.

Next, the authors demonstrated the usefulness of these “organoids” in modeling damage due to Zika virus. After exposing the generated organoids to Zika, the authors measured the cellular responses of the tissue, demonstrating the ability to use these tissues to model the disease.  Given the recent epidemic of Zika virus in the Western Hemisphere, which focused attention on the virus’s effects on the human brain, in addition to microcephaly and other birth defects when the disease is transmitted from pregnant mothers to their children, understanding how Zika affects the developing brain is key to determining how to prevent the damage it causes and possibly repairing it. Reliable models of brain development are necessary, and the UCLA team’s findings seem to indicate that they’ve found one.

Rebuilding Brain Circuits After Injury

Among the issues in the prevention and treatment of head injury is that we still lack complete information about the mechanism underlying these injuries.  However, a key piece of basic research recently published by a team at the University of North Carolina, Chapel Hill, demonstrates that a key aspect of this mechanism occurs in the axons, which are the stalks that grow from neurons to signal to each other. In an article published in Nature Communications, the team, led by Anne Marion Taylor, Ph.D., assistant professor of biomedical engineering at UNC, reports on using microfluidics technology to determine how neurons react when axons are severed. The authors found that damage to axons causes a compensatory loss of collateral connections to neighboring neurons. This loss in connectivity could be reversed by adding a protein, netrin-1, into the solution surrounding the neurons. Although netrin-1 was already known for its importance in rebuilding damaged axons, this work showed that netrin-1 has more widespread effects in rebuilding neural circuits after trauma.

Seeing Inside the Body

One of the key problems with minimally invasive surgical procedures is difficulty in shining sufficient light in the target region to see and manipulate tissue during surgery. Glass filaments are currently used, but they pose a health risk because they can break off in the body. A new citrate polymer fiber invented by scientists at Penn State University represents a much safer alternative to glass filaments. Reporting in Biomaterials, the scientists, led by Jian Yiang, Ph.D., associate professor of biomedical engineering at Penn State, describe how they developed the fiber and show how much less likely this polymer filament is to break when manipulated. If biocompatibility tests show that this polymer does not affect tissue health, it could eventually appear in surgical microscopes and make glass filaments a thing of the past.
Creating better illumination tools is one way of seeing inside the body. An elegant device developed by a team including MIT biomedical engineer Giovanni Traverso, Ph.D., consists of a proof-of-concept ingestable sensor that attaches to the stomach lining and can provide upper gastrointestinal system information for two days. The team reports on the device in a recent issue of Nature Biomedical Engineering. Unlike earlier ingestable diagnostic devices, the sensor developed by Dr. Traverso and his colleagues uses the contraction of the gut to power the device. It also surpassed pill-sized ingestable cameras by providing data from a longer time period.

Implants That Grow With Chilren

Using implants to treat medical problems in children is difficult for one simple reason: children can quickly outgrow their devices. The problem has been particularly acute among pediatric cardiac surgeons, for whom implants are commonly used devices. Now, thanks to collaboration between surgeons and a team including Jeffrey Karp, Ph.D., a Harvard biomedical engineer, valve implants that grow with patients could be here soon. Inspired by the clever design of a Chinese finger trap, the collaborators developed an implant that grows longer but thinner over time. They report on their device in Nature Biomedical Engineering, including its proof-of-principle testing in growing piglets. Based on these data, the study authors will continue to adapt and develop the device.

Say What?

Humans are especially good at listening to many voices at once or focusing on one voice in a crowded room. However, we really don’t know how we do this so well. Scientists at Imperial College London (ICL) solved part of this mystery. Reporting in eLife, the ICL authors developed a mathematical method to measure how the response to speech in a person’s brainstem changed when that person’s attention moved from one person to another. Perceptible changes in brainstem activity occurred when a person was intently listening to someone, and it disappeared when the person ignored speech. In addition to supplementing what we already know about how the brain stem participates in sensory tasks, the ICL team’s findings mean that damage to the brainstem – common to several neurological disorders – can easily affect how we process speech and interact with each other.

Chairs for BMES ’19 to Include Burdick

chairsJason Burdick, Ph.D., who is a professor in the University of Pennsylvania’s Department of Bioengineering, has been named one of the three chairs of the 2019 annual meeting of the Biomedical Engineering Society (BMES), which be held here in Philadelphia on October 16-19. Dr. Burdick will share this position with two other Philadelphians: Alisa Morss Clyne, Ph.D., an associate professor of mechanical engineering and mechanics at Drexel University; and Ruth Ochia, Ph.D., an associate professor of instruction in bioengineering at Temple University. Drs. Burdick, Clyne, and Ochia will share the responsibility for planning the meeting and chairing it once it is in session.

“I am very happy to be appointed as a program chair for the 2019 BMES meeting in Philadelphia, along with Alisa Morss Clyne of Drexel University and Ruth Ochia of Temple University,” Dr. Burdick said when asked about the honor. “The three of us felt that it was important to represent the various biomedical engineering research and education programs within the city of Philadelphia, since the meeting will be held here.  There is such a wealth of biomedical engineering efforts in Philly that provides great opportunities to engage in outreach and interaction with both the community and local industry during the meeting.”

Week in BioE (October 13, 2017)

Seeing and Repairing Damaged Heart Vessels

angiography
Immunofluorescent staining for F-actin filaments (green) and nuclei (blue) in neonatal cardiomyocyte

Two common diagnostic procedures in cardiology are intravascular ultrasound and cardiac angiography. These procedures are performed to quantify the amount of plaque affecting a patient’s blood vessels. This information is vital because it helps to determine how advanced heart degree is, as well as guiding treatment planning and even the course of bypass surgery. However, the current technologies used for these procedures have significant limitations. Although conventional angiography can help to quantify the plaque burden, it does not offer any information about how much of the diameter of a vessel is blocked. Intravascular ultrasound is very good at quantifying plaque burden, but it is poor at identifying smaller features of compromised blood vessels.

One solution suggested to these issues is the combination of these imaging technologies into a single multimodal technique. Scientists led by Laura Marcu, Ph.D., professor of biomedical engineering at the University of California, Davis, invented a method combining intravascular ultrasound with multispectral fluorescence lifetime imaging (FLIM). As published in Scientific Reports, the device resembles a typical cardiac catheter but contains an optical fiber within the catheter that emits fluorescent light to characterize the plaque components before treatment.

Dr. Marcu and her colleagues tested their new device in live pigs and in human coronary arteries obtained from cadavers. The fluorescence data acquired with the device were comparable to those acquired with traditional fluorescence angiography. Moreover, the device could acquire data without having to administer a contrast agent, which can be dangerous in some patients due to allergies or weakened kidneys. The authors are currently seeking FDA approval to test their combined catheter in humans.

In addition to treating vessels before a heart attack can occur, there is new work showing how to efficiently repair heart tissue after a heart attack. A team of scientists collaborating among Clemson University, the Medical University of South Carolina,  the University of South Carolina, and the University of Chicago has received a $1.5 million grant from the National Institutes of Health to examine a treatment that combines stem cells with nanowires. The principal investigator on the grant is Ying Mei, Ph.D., who is assistant professor of bioengineering at Clemson. Dr. Mei’s team mixes stem cells with nanowires so that they form spheroids that are larger than single cells and thus less likely to wash away. In addition, the investigators hope that the spheroids will mitigate the issue of the transplanted cells and the recipient’s heart beating at different rhythms.  If successful, the group’s treatment paradigm could be a major step forward in stem cell therapies and cardiology.

Look, Up in the Sky!

Drones became famous when deployed on battlefields for the first time a decade ago. Since then, they’ve been adopted as a technology for a variety of purposes. For example, Amazon introduced delivery drones almost a year ago, and it has plans to expand its drone fleet enormously in coming years. It was only a matter of time before engineers began to imagine medical applications for drones.

Engineers in Australia and Iraq recently investigated whether a drone could be used to monitor cardiorespiratory signals remotely. They reported their findings in BioMedical Engineering OnLine. The authors used imaging photoplethysmography (PPG), which employs a video camera to detect visual indications on the skin of heart activity. They also applied advanced digital processing technology due to the tendency of PPG to be affected by sound and movement in the area of detection. By testing the combined technologies in 15 healthy volunteers, the authors found that their data compared well with several traditional techniques for monitoring vital signs. Among the possible applications that the authors imagine for this technology is battlefield triage performed remotely using drones. In the meantime, they will seek to fine-tune the technology’s abilities.

Concussion Distressingly Common

A research letter published in a recent issue of JAMA reports that a study conducted in Canada found that one in five adolescents sustained a concussion on at least one occasion. Of the approximately 20% of the study respondents who had experienced concussions, one quarter had suffered more than one. The letter is particularly relevant to the United States because of the similar popularity in Canada of contact and semicontact sports such as ice hockey and football. In addition, the study included more than 13,000 teenagers, lending significantly reliability to the conclusions.

Ending the Time of Cholera

Although largely eradicated in the developed world, cholera remains a major public health issue in the Global South and other parts of the developing world. The disease is a bacterial infection that causes severe gastrointestinal distress. Because the disease is transmitted via water, effective public sanitation is a core requirement of an effective prevention campaign.

One technology being deployed in this fight is a smartphone microfluidics platform that can determine the presence of the pathogen that causes cholera in a sample and report the data almost immediately to public health authorities. This technology was produced by a company called PathVis, which was spun off at Purdue University based on science produced the laboratories of Tamara Kinzer-Ursem, Ph.D., and Jacqueline Linnes, Ph.D., both of whom are assistant professors in Purdue’s Weldon School of Biomedical Engineering. There are plans to test PathVis in Haiti and to expand it to detect other diseases in the future.

The Latest on CRISPR

CRISPR/Cas9 is the biggest bioengineering story to come along in some time — certainly the biggest in genetic engineering. But the mere fact that it’s here and already being used in animals and in human cell lines doesn’t mean that the story is over.  For instance, the Cas9 protein, which CRISPR deploys as part of its gene editing process, is currently developed most often using a viral vector. However, this system of delivery has certain drawbacks, not the least of which is a host immune system response when levels of the deployed viral vector reach the levels necessary for CRISPR to work.

A recent study published in Nature Biomedical Engineering reports on the successful use of gold nanoparticles to deliver Cas9. The new delivery system, called CRISPR-Gold, could obviate the need to use a viral vector as part of the CRISPR induction process. So far, the authors, led by University of California, Berkeley, bioengineers Irina Conboy, Ph.D., and Niren Murthy, Ph.D., have only used CRISPR-Gold in mice, but their successful results indicate that nonviral delivery with CRISPR is possible, so CRISPR could be used for more than previously thought.

 

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.