Week in BioE (July 9, 2018)

A New Treatment for Joint Dysfunction

TMD is a common condition affecting movement of the jaw

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

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

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

Advances in Autism Research

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

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

Penn Professor’s Groundbreaking Bioengineering Technology

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

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

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

New Prosthetics Will Have the Ability to Feel Pain

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

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

People and Places

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

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

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

 

Week in BioE (April 17, 2018)

Mosquito Bites Inspire Brain Implants

mosquitoesWe’ve talked before at this site about the difficulty involved in implanting devices in the brain. One chief problem is that any implant to record brain signals causes small amounts of damage that causes signal quality to deteriorate over time. One approach to overcoming this problem uses flexible materials that can move with brain tissue movement, rather than resisting the movement to cause damage.

One of the more recent designs was inspired by an NPR report on mosquitoes. Dr. Andrew Shoffstall, a postdoc in the lab of Jeffrey Capadona, PhD, Associate Professor of Biomedical Engineering at Case Western Reserve University (CWRU), saw the report and used the mechanism that mosquitoes use when biting people to design a new device, which the CWRU team describes in an article in Scientific Reports.

The authors studied the buckling force when mosquitoes puncture the skin, using this design to invent new microneedles for brain implant recordings. The group fashioned a 3D-printed plastic device to mimic the process used by the mosquito. They tested the device, first mechanically and then in rat brains, finding that the device could successfully implant a microelectrode in 8 out of 8 trials. Certainly the device will require much more rigorous testing, but if successful, it could change the way implants are inserted into human patients.

Big News About Small Things

Speaking of implants, they continue to decrease in size.  Scientists at Stanford University created a wireless device that is the size of a rice grain. Reporting in IEEE Transactions on Biomedical Circuits and Systems, the scientists, led by Amin Arbabian, PhD, Assistant Professor of Electrical Engineering at Stanford, and including Dr. Felicity Gore, a postdoc in the Department of Bioengineering, describe the design and fabrication of this implant. The implant was designed to stimulate peripheral nerves using either platinum electrodes connected directly to the nerve or light from a blue LED to stimulate optogenetic channels expressed in the neurons. The group conducted an in vivo experiment, using the device to stimulate the sciatic nerve of a frog, and they showed the device’s feasibility. Powered by ultrasound transmitted through the skin, the device has no external wire connections. The size of the implant, combined with its ability to target single nerves, could revolutionize how pain is treated, among other applications. 

Meanwhile, here at Penn, the creation of very small things is getting a very big boost. In a new collaboration among schools and centers, the university’s Center for Targeted Therapeutics and Translational Nanomedicine has established the Chemical and Nanoparticle Synthesis Core (CNSC). The director, Andrew Tsourkas, PhD, is a Professor in the Department of Bioengineering and the Undergraduate Chair. The mission of the CNSC is to provide a concierge level service for Penn faculty interested in synthesizing new molecules for therapy development, as well as new nanoparticles for advanced diagnostics.

A Leap Forward With Stem Cells

Over the last decade, stem cell research has resulted in significant contributions to medical science. One application is the modeling of organs and organ systems for studies before in vivo investigations. However, stem cell projects involving the heart have been limited by the inability to get these cells to a mature state.

However, in a letter published in Nature, researchers at Columbia University and the University of Minho in Portugal describe how they used electrical and mechanical stimulation of human induced pluripotent stem cells to create more mature cells. The authors, led by Gordana Vunjak-Novakovic, PhD, University Professor and Mikati Foundation Professor of Biomedical Engineering and Medical Sciences at Columbia, describe how, after four weeks of culturing under the described conditions, the cells displayed multiple characteristics of maturity, although some electromechanical properties of mature cells remained lacking. These findings show that engineering the physical environment that surrounds cells during development is a key factor for the engineering design of replacement tissue.

Individualizing First Aid

Personalized medicine has begun to affect the way that doctors treat several diseases with genetic bases, notably cancer. However, first aid has lagged a bit behind in personalization, in part because the urgency of first aid care emphasizes fast, practical solutions that work for everyone. However, in a presentation at Philadelphia’s Franklin Institute last month, Jonathan Gerstenhaber, PhD, Assistant Professor of Instruction in the Department of Bioengineering at Temple University, demonstrated a prototype device that uses 3D printing technology to produce personalized bandages when they are needed.

Dr. Gersternhaber created a 3D printer that will print bandages directly onto the skin of the patient. Customizing the fit of the bandage with the printing technology would make them last longer, and the ‘on demand’ production of the bandage provides a chance to individualize the bandage design even in the urgent care setting. The device uses electrospinning technology to create bandages from soy protein, which, as a natural substance, can actually speed healing. Having completed the prototype, Dr. Gerstenhaber has moved onto portable models, as well as a larger device that can make bandages across a larger surface area.

Solving Two Problems in Glaucoma Care 

Glaucoma is one of the earliest medical uses for cannabis, commonly known as marijuana. The cannabinoids in the cannabis plan have the effect of lowering intraocular pressure, which is the primary mechanism underlying glaucoma. However, the intoxicating effects of cannabis pose a problem for many patients. Thus, most patients still rely on eyedrops containing other drugs. Getting the dosage correct with eyedrops is tricky, however, because of the continual blinking and tearing of the eye.

Now, in a new article published in Drug Delivery and Translational Research, a team of researchers led by Vikramaditya G. Yadav, PhD, Assistant Professor of Chemical and Biological Engineering at the University of British Columbia, describes how they developed a nanoparticle hydrogel medication to deliver a cannabinoid. The authors tested the gel in situ, with good results. The authors imagine that such a gel could be used by patients at bedtime, and during the night, the drug would be dispensed by the gel and be gone by morning.

Week in BioE (November 10, 2017)

Building Muscle at the Cellular Level

mitochondria
Cells with the mitochondria in green.

We’ve known for many years that exercise is good for you, but it was less clear how muscle strength and stamina were assembled at the molecular level. Based the principle that the health of mitochondria – a key organelle within the muscle cell – regulates muscle health, recent work identifies some of the key signaling pathways in vivo that can switch a cell between degrading damaged mitochondria or creating new mitochondria. Zhen Yan, M.D., Ph.D., of the University of Virginia, used a fluorescent reporter gene (MitoTimer) to “report back” the information for individual mitochondria in muscle cells prior to and following exercise. The results reported in a recent issue of Nature Communications show very clearly that mitochondria can switch a muscle cell’s fate. Dr. Yan’s research team identified a new signaling pathway within skeletal muscle that is essential to mitophagy. Knowledge of this pathway could help to develop a variety of therapies for diseases of the muscles or damage to the muscles due to injury.

Understanding How the Brain Processes Visual Data

As a model for how the brain “computes” the information surrounding all of us, researchers have studied how visual information is processed by the brain. One method for investigating this question is the use of artificial neural networks to recognize visual information that they have previously “seen.” A recent article in Cerebral Cortex details how a team at Purdue University, led by Zhongming Liu, Ph.D., Assistant Professor of Electrical and Computer Engineering and Biomedical Engineering, used an artificial neural network to predict and decode information obtained with functional magnetic resonance imaging (fMRI). By collecting fMRI brain activation data when people watch movies, the artificial neural network could generate feature maps that strongly resembled the objects depicted by the initial stimuli. Available now in open access format, the team at Purdue intends to repeat these experiments with more complex networks and more detailed imaging modalities

Preventing Prosthesis-related Infection

Prostheses have improved by leaps and bounds over the years, with the development of osseointegrated prostheses — which are fused directly to the existing bones — a major step in this evolution. However, these prostheses can lead to severe infections that would require the removal of the prosthesis. These problems have been seen more commonly over the last decade or so in the military, where wounded soldiers have received prostheses but suffered subsequent infections.

In a major step forward to address this issue, Mark Ehrensberger, PhD, assistant professor of biomedical engineering at SUNY Buffalo, is the principal investigator on a two-year $1.1 million grant from the Office of Naval Research in the U.S. Department of Defense, awarded for the purpose of investigating implant-related infections. Initial research by Dr. Ehrensberger, who shares the grant award with scientists from the departments of orthopaedics and microbiology and immunology, showed that delivering electrical stimulation to the site of the prosthesis could be effective. One method the team will investigate is using titanium from within the implants themselves to conduct the current to the site.

Success with this grant could mean that patients receiving prostheses show better recovery rates and much lower rates of rejection. It could also reduce the antibiotics used by such patients, which would be a welcome outcome given the increasing rates of antibiotic resistance in health care.

Bioengineering Treatments for Depression

Depression is a largely invisible illness, but it brings with it a massive burden on both the patient and society, with health care costs exceeding $200 billion per year in the U.S. alone. Different drugs are used to treat depression, but all have significant side effects. Psychotherapy also has some effectiveness, but not all patients are helped with therapy.

One promising alternative to treat depression uses transcranial magnetic stimulation, but the devices used in this treatment are often cumbersome. In response to calls to develop more accessible forms of therapy for depression, a startup company in Sweden called Flow Neuroscience has developed a wearable device that uses transcranial direct-current stimulation targeted at the left frontal lobe. The device is noninvasive and is smaller than a sun visor, and the company claims it will be relatively inexpensive (estimated at $750). Flow Neuroscience is in the process of applying for regulatory approval in the European Union.

People and Places

United Kingdom Chancellor of the Exchequer Philip Hammond  has announced that the British government will provide £7 million (approximately $9.2 million) in funding to create the UK Centre for Engineering Biology, Metrology and Standards. The government is collaborating with the the Francis Crick Institute in London, with the goal of supporting startup companies in Great Britain dedicated to using engineering and the biological sciences to develop new products.

Closer to home, the Universities of Shady Grove — a partnership of nine Maryland public universities where each university provides its most heavily demanded program — have begun construction on a $162 million biomedical sciences building. The building is slated for completion in 2019 and is expected to nearly double the enrollment at Shady Grove.

Here at Penn, Adam Pardes, a current Ph.D. candidate in our own Department of Engineering, is one of the cofounders of NeuroFlow, a company developing a mobile platform to track and record biometric information obtained from wearables.  NeuroFlow recently received $1.25 million in investments to continue developing its technology and ultimately bring it to market. Congratulations, Adam!

Finally, California State University, Long Beach, is our newest national BME program this fall. Burkhard Englert, Ph.D., professor and chair of the Department of Computer Engineering and Computer Science at CSULB, heads the new program as interim chair until a permanent chair is hired.

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.

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 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.