Week in BioE (June 7, 2018)

Vision of the Future

corneal transplantation
A human eye that received a cornea transplant one year postoperatively.

Disorders of or damage to the cornea — the clear covering over the lens of the eye — can be threatening to vision, and for the last century, corneal transplantation has been a cornerstone of treatment for these conditions. However, corneal transplants are complicated by two key facts: first, as with virtually all transplant procedures, donor organs are in short supply; and second, rejection is common, and recipients of transplants face repeated procedures or a lifetime of steroid eyedrops to prevent rejection.

One way of obviating these issues is the use of synthetic materials, which can now be manufactured with three-dimensional printing. In a new study from scientists at the Institute of Genetic Medicine at Newcastle University in the UK, to be published this summer in Experimental Eye Research, synthetic corneal tissue was 3D printed using a bioink loaded with encapsulated keratocytes (corneal cells), in combination with computer modeling based on actual corneas. The study is only proof to show that printing a biological replicate of the cornea is possible, but it lays the groundwork for future studies in animals.

Engineering Brain Recovery

One of the reasons why stroke is such a damaging event is the inability of damaged brain tissue to regenerate. Angiogenesis, the growth of new blood vessels, can help to regenerate brain tissue but properly guiding the process of angiogenesis is rather difficult.

However, a new report in Nature Materials indicates success using an injectable biogel for this purpose. In the report, a team led by Tatiana Segura, PhD, Professor of Biomedical Engineering at Duke with colleagues at UCLA, details its engineering of an injectable gel using nanoparticles consisting of heparin (a blood-thinning agent to prevent unwanted blood clotting) and vascular endothelial growth factor (VEGF) to stimulate brain regeneration. After injecting the gel in a mouse model of stroke, the mice showed a significant improvement in recovery compared to animals not receiving the engineered nanomaterial.

Here at Penn, D. Kacy Cullen, PhD, Research Associate Professor of Neurosurgery in the Perelman School of Medicine, has been investigating the use of implantable tissue-engineered brain pathways to treat and perhaps reverse the effects of neurodegnerative diseases like Parkinson’s disease. Penn Today has the story, with video of Dr. Cullen and photos and quotes from several of our own Bioengineering students.

Streamlining Environmental Bioengineering

Outside of the health sciences, bioengineering has applications in diverse fields, including energy development and environmental protection. Biofuels are one application for bioengineering that received a major boost recently. In an article published in NPJ Systems Biology and Applications, engineers from the US Department of Energy’s Lawrence Berkeley National Laboratory describe how they used machine learning to better predict the ability of engineered microbes to produce biofuel. With this information, they can then better adjust fuel-producing microbial pathways to maximize production. The machine learning model is a significant improvement over earlier, traditionally algorithmic approaches requiring complex differential equations. The time saved could, over generations of adjustments, result in a significant increase in output.

More on Pilots

Last week, we discussed how the cognitive load borne by airline pilots differs between simulated and real flight. Other scientists, it turns out, are looking at ways that pilots — in particular, fighter pilots — can overcome fatigue. With more than $1 million in grants from the US Department of Defense, Merhavan Singh, PhD, Dean of the Graduate School of Biomedical Sciences at the University of North Texas Health Science Center, and  Kai Shen, PhD, Associate Professor in the  Department of Chemistry and Forensic Science at Savannah State University in Georgia, are investigating compounds targeting the sigma 1 receptor, which the scientists believe could combat fatigue and also have neuroprotective effects if activated. This is particularly important among fighter pilots serving in conflict, who are often sleep deprived but must remain alert during missions.

People and Places

Having achieved success in its mission, the University of Alabama at Birmingham’s PREP Scholars Program, which supports underrepresented minority students in pursuing graduate study in bioengineering and biomedical engineering, has received an additional $1.8 million in support from the National Institutes of Health. The money will enable the funding of 40 students over the next five years.

Jeffrey Collins Wolchok, PhD, and Kartik Balachandran, PhD, both associate professors in the Department of Biomedical Engineering at the University of Arkansas, have received a $375,000 grant from the National Science Foundation to study the long-term effects of multiple concussions on the brain. With the increased emphasis in the scientific community and media on traumatic brain injury and chronic traumatic encephalopathy, including among former athletes, the two scientists will develop brain on a chip technology to examine the issue.

Finally, this week, the Best College Reviews website published its Top 10 list of online Master’s programs in biomedical engineering. Purdue University’s program finished in first place, with appearances on the list by Colorado State, UC Riverside, Stevens Tech, and Worcester Tech.

Week in BioE (May 29, 2018)

Virtual Biopsy for Melanoma

virtual biopsy
Melanoma cells stained to show cell nuclei (blue), podosomes (yellow), actin (red), and an actin regulator (green).

Melanoma is a common form of skin cancer that is most often successfully treated by removal of the cancerous cells. However,  malignant forms of melanoma can metastasize and become deadly. The significance of malignant melanoma is evident in its incidence – melanoma is the fifth most common cause of deaths from cancer in the US. Treating melanoma relies on using biopsy samples to determine the virulence of the cancer. However, the biopsy process is invasive and painful, and it can even be disfiguring.

Addressing this issue, Jesse Wilson, PhD, Assistant Professor in the Department of Electrical and Computer Engineering and in the School of Biomedical Engineering at Colorado State University (CSU), is developing a virtual biopsy for the disease. Funded by a Young Investigator Award from the Melanoma Research Alliance and a grant from the Colorado Clinical and Translational Sciences Institute, Dr. Wilson’s virtual biopsy uses multiphoton microscopy, which normally requires the use of a costly short-pulse laser for optimal visualization; his research seeks to obviate the need for laser, thus rendering the process more broadly available. 

Dr. Wilson intends to begin testing of his biopsy device on dogs from CSU’s veterinary school. Dogs also develop malignant melanoma, so the device will be used to gather data about each lesion that a dog develops. Once the imaging data are collected, the dogs will undergo normal biopsy and, if needed, treatment. In parallel, Dr. Wilson’s imaging algorithm will process the microscopy data collected prior to the biopsy, score it as malignant or not, and compare the predictions with the actual biopsy results to determine the new technique’s accuracy.

A Clue to Consciousness

Among the great mysteries in neuroscience is the nature of consciousness — that aspect of our psyche that allows us to observe that we are aware. We know that we have consciousness, but we aren’t sure why we do, nor do we fully understand the biological mechanisms that underlie consciousness.

A new study from scientists at Washington University in St. Louis might offer some clues, however. In the study, published in Neuron, the authors used a combination of calcium and hemoglobin imaging in mice to detect infra-slow spatiotemporal trajectories — essentially brain waves that are qualitatively different from other traditional electrical activity waves measured in the brain. These new waveforms were much slower than the activity of other traditional activity waves, and they traveled through different areas of the animals’ brains. The direction of the waves, moreover, changed on the basis of the level of consciousness of the mice.

Closer to home (and to humans), in a new article in Frontiers in Human Neuroscience, Hasan Ayaz, PhD, Associate Research Professor in the
School of Biomedical Engineering, Science and Health Systems at Drexel University, in collaboration with scientists from France, reports that the cognitive load of airline pilots differs significantly between pilots in the actual cockpit, compared to those using flight simulators. Dr. Ayaz and his colleagues used functional near infrared spectroscopy (fNIRS) for their comparisons. A future step for this research will be to integrate flight data recordings with the fNIRS data.

3D Printing Now Sweeter

Three-dimensional printing has become a vital resource in tissue engineering. However, the ability of commercial 3D printing technology to produce water-soluble glass — a key compound used in many tissue engineering processes — has been elusive because of the specific properties of the carbohydrates used to create this glass, which do not work with the technology used in available 3D printers.

However, this issue could be closer to a solution. In a new article in Additive Manufacturing, a team of scientists led by Rohit Bhargava, PhD, Founder Professor of Engineering in the Department of Bioengineering at the University of Illinois in Urbana-Champaign, reports that they have solved some of these problems. Using isomalt, a type of sugar alcohol, for their experiments, the authors were able to determine the characteristics inherent in the material necessary for 3D printing, as well as modeling the type of machinery necessary to use isomalt in a 3D printing process. Work on creating the 3D printing model recently published is still under way, but video of a bridge model has been published online here.

Seeing Like a Bat

Earlier this month, CLEO (the Conference on Lasers and Electro-Optics) held its annual meeting in San Jose, with a bioengineering contingent out in full force. Nader Engheta, PhD, the H. Nedwill Ramsey Professor with appointments in the Departments of Bioengineering, Electrical and Systems Engineering, and Materials Science and Engineering, was there and gave an interview with Optics & Photonics News. In the interview, Dr. Engheta discusses, among other things, bioinspired polarization — a developing field that seeks to enable people to see polarized light, which is visible to some animals, such as bats, but not to the human eye.

People and Places

Elon University in North Carolina will expand its current offerings in engineering in the coming year. In addition to a dual-degree program, Elon will offer for the first time an undergraduate degree program in engineering with an available concentration in biomedical engineering.  Sirena Hargrove-Leak, PhD, has been named director of the new program.

Week in BioE (May 22, 2018)

Ultrasound Helmet Provides Perioperative Images

ultrasound helmet
Normal ultrasound image of an infant’s brain

As we’ve mentioned here before, surgery on the brain is particularly difficult because of the limited visibility afforded to the surgical field and the complexity of the organ. Because the brain’s gray matter can be easily damaged, a false move by a surgeon can have a lifetime of consequences. Better visualization during surgery could go a long way toward preventing accidental damage by the surgeon and minimize the removal of healthy brain tissue during tumor removal. However, ultrasound imaging of the brain has remained difficult because of the tendency of ultrasound waves to bounce off the skull.

To help solve this problem, a biomedical engineer at Vanderbilt University  developed an ultrasound helmet to create perioperative ultrasound images of the brain. It could also provide a new variety of platform for brain-machine interfaces. According to Brett Byram, PhD, Assistant Professor of Biomedical Engineering at Vanderbilt, the helmet will eventually combine ultrasound with electroencephalography (EEG) to simultaneously visualize the brain and record its activity.  Dr. Byram used a machine learning-based technique called aperture domain model image reconstruction (ADMIRE) to overcome the technical obstacle of ultrasound waves transmitting through the skull. 

Although the initial thought of how to apply this technology was surgical, Dr. Bryram believes that the ability to detect blood flow to different parts of the brain in real time using ultrasound could facilitate the creation of technologies that would use this blood flow information, smoothed using ADMIRE, and EEG data to communicate with implants or robotic extensions to perform tasks.

A Roach Motel for Cancer

One key to curing cancer is preventing its spread, called metastasis. The mechanisms underlying metastasis are becoming clearer after years of research. Typically, the spread of cancer is the result of cancerous cells shed by a tumor affecting another organ after traveling via the bloodstream or lymphatic system. Unfortunately, sometimes this shedding is caused by the surgical procedure to remove the tumor. Therefore, preventing metastasis requires preventing these cells from circulating during and after the surgical procedure.

At the University of Texas at Arlington (UTA), Liping Tang, Ph.D., Professor of Biomedical Engineering at the University of Texas at Arlington, has patented what he calls a “roach motel” for cancer cells. Dr. Tang’s device, which is implanted under the skin, circulates cells of its own that attract circulating metastatic cells. The result of the device is the trapping of the cancer cells within the device and preventing them from traveling further. In vitro testing has been quite successful in a variety of cancers. Preclinical testing in animals will be the next step.

Injectable Alcohol Sensor Could Augment Treatment Programs

A few weeks ago, we detailed here how a scientist is developing DNA-based drug and alcohol screening tests. Recently a group of bioengineers at the University of California–San Diego (UCSD), led by Drew A. Hall, PhD, Assistant Professor of Electrical and Computer Engineering and an affiliate professor in the Department of Bioengineering at UCSD, has developed an injectable biosensor that can communicate blood alcohol levels to a wearable device. The sensor is a complementary metal–oxide semiconductor approximately 1 square millimeter in size and is designed for implantation under the skin surface. If in vivo testing proves successful, the system could be used as part of holistic approaches to preventing alcohol abuse among recovering alcoholics.

A Temperature-measuring Microscope

If you’ve used a microscope, then you’ve probably noticed that the samples viewed using microscopes are almost always on glass slides placed beneath the lens of the device. Now, in an article recently published in Nature Communications, an engineering team reports on their invention of a slide that can also measure temperature fluctuations in samples while maintaining microscopic imaging capability. Ruogang Zhao, PhD, assistant professor in the University at Buffalo Department of Biomedical Engineering, along with colleagues from our sister Departments of Electrical and Systems Engineering and Materials Science and Engineering here at Penn, coated a normal slide with 20-nanometer layers of gold activated by an external laser. Applications of the technology are numerous, and will be accelerated through mass production of slides, which the authors estimate would cost less than 10 cents each.

People and Places
Two large donations make our news this week. First, the University of Southern California received a $10 million gift from a retired ophthalmologist and his wife. The Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics is being led by Mark S. Humayun, MD, PhD., Professor of Ophthalmology, Biomedical Engineering, and Cell and Neurobiology at USC. Across the country, the University of Maryland School of Medicine will establish the Robert E. Fischell Center for Biomedical Innovation with a $20 million gift from Robert Fischell, an inventor and holder of 200 patents. Distinguished University Professor and founding chair of the Fischell Department of Bioengineering William E. Bentley, PhD, will head the Fischell Center.

Also, it’s May, which means graduate news. Two special congratulations are in order. First, we congratulate Rowan University in New Jersey for graduating its first cohort of three newly minted PhDs in Biomedical Engineering. Also at the University of California at Davis, Tanishq Abraham will graduate next month with a Bachelor’s degree in Biomedical Engineering. In case that doesn’t sound like big news, bear in mind that Tanishq is only 14 years old. Tanisq will continue at Davis in studying in an MD/PhD program, which he hopes to finish before finishing his second decade of life.

Finally, we congratulate Brian Holland, MD, who has been named the new chief of pediatric cardiology at the University of Louisville. Dr. Holland is an alumnus of Penn Bioengineering, graduating summa cum laude in 1996.

Week in BioE (May 10, 2018)

Advances in Cancer Detection

glioblastoma
Tumor-brain-interface in a glioblastoma biopsy specimen.

Among the deadliest and most difficult to treat types of cancer is glioblastoma, an especially aggressive form of brain cancer. Widely available imaging techniques can diagnose the tumor, but often the diagnosis is too late to treat the cancer effectively. Although blood-based cancer biomarkers can provide for earlier detection of cancer, these markers face the difficult task of crossing the blood-brain barrier (BBB), which prevents all but the tiniest molecules from moving from the brain to the bloodstream.

A study recently published in Scientific Reports, coauthored by Hong Chen, PhD, Assistant Professor of Biomedical Engineering at Washington University in St. Louis (WUSTL), reports of successful deployment of a strategy consisting of focused ultrasound (FUS), enhanced green fluorescent protein (eGFP), and systemically injected microbubbles to see if the BBB could be opened temporarily to allow biomarkers to pass from the brain into the bloodstream. The authors used eGFP-activated mouse models of glioblastoma, injecting the microbubbles into the mice and then exposing the mice to varying acoustic pressures of FUS. They found that circulating blood levels of eGFP were several thousand times higher in the FUS-treated mice compared to non-treated mice, which would significantly facilitate the detection of the marker in blood tests.

The method has some way to go before it can be used in humans. For one thing, the pressures used in the Scientific Reports study would damage blood vessels, so it must be determined whether lower pressures would still provide detectable transmission of proteins across the BBB. In addition, the authors must exclude the possibility of FUS unexpectedly enhancing tumor growth.

In other body areas, with easier access from tissue to the bloodstream, engineers have developed a disease-screening pill that, when ingested and activated by infrared light, can indicate tumor locations on optical tomography. The scientists, led by Greg M. Thurber, PhD, Assistant Professor of Biomedical and Chemical Engineering at the University of Michigan, reported their findings in Molecular Pharmaceutics.

The authors of the study used negatively charged sulfate groups to facilitate absorption by the digestive system of molecular imaging agents. They tested a pill consisting of a combination of these agents and found that their model tumors were visible. The next steps will include optimizing the imaging agent dosage loaded into the pill to optimize visibility. The authors believe their approach could eventually replace uncomfortable procedures like mammograms and invasive diagnostic procedures.

Liquid Assembly Line to Produce Drug Microparticles

Pharmaceuticals owe their effects mostly to their chemical composition, but the packaging of these drugs into must be done precisely. Many drugs are encapsulated in solid microparticles, and engineering consistent size and drug loading in these particles is key. However, common drug manufacturing techniques, such as spray drying and ball milling, produce uneven results. 

University of Pennsylvania engineers developed a microfluidic system in which more than ten thousand of these devices run in parallel, all on a silicon-and-glass chip that can fit into a shirt pocket, to produce a paradigm shift in microparticle manufacturing. The team, led by David Issadore, Assistant Professor in the Department of Bioengineering, outlined the design of their system in the journal Nature Communications.

The Penn team first tested their system by making simple oil-in-water droplets, at a rate of more than 1 trillion droplets per hour. Using materials common to current drug manufacturing processes, they manufactured polycapralactone  microparticles at a rate of ‘only’ 328 billion particles per hour. Further testing backed by pharma company GlaxoSmithKline will follow.

Preventing Fungal Infections of Dental Prostheses

Dental prostheses are medical devices that many people require, particularly as they age. One of the chief complications with prostheses is fungal infections, with an alarming rate of two-thirds among people wearing dentures. These infections can cause a variety of problems, spreading to other parts of the digestive system and affecting nutrition and overall well-being. Fungal infections can be controlled in part by mouthwashes, microwave treatments, and light therapies, but none of them have high efficacy.

To address this issue, Praveen Arany, DDS, PhD, Assistant Professor, Department of Oral Biology and Biomedical Engineering at SUNY Buffalo, combined 3D printing technology and polycaprolactone microspheres containing amphotericin-B, an antifungal agent. Initial fabrication of the prostheses is described in an article in Materials Today Communications, along with successful in vitro testing with fungal biofilm. If further testing proves effective, these prostheses could be used in dental patients in whom the current treatments are either ineffective or contraindicated.

People and Places

West Virginia University has announced that it will launch Master’s and doctoral programs in Biomedical Engineering. The programs will begin enrolling students in the fall. The graduate tracks augment a Bachelor’s degree program begun in 2014.

Week in BioE (May 1, 2018)

To Bee or Not To Bee

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

 

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

 

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

Advances in Visualization

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

 

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

 

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

Turning Red

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

Absorbable Stents for Cardiac Care

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

 

People and Places

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

 

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

Week in BioE (April 24, 2018)

Pushing the Limits of Imaging

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

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

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

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

Smart Shunt for Hydrocephalus

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

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

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

DNA-based Drug Testing

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

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

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

People and Places

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

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

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

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 (April 10, 2018)

‘Kelp’ Is on the Way!

kelp
Chondrus crispus, a common red algae from which carrageenan is extracted.

Medicine has made tremendous strides since the 1960s, as evidenced by the increased survival rates of combat soldiers since Vietnam. Nevertheless, blood loss remains the most common cause of death of soldiers on the battlefield. Finding a way for medics or soldiers to stop bleeding can significantly cut down on these deaths, but current approaches are either very expensive or not easy to use in combat.

According to a new paper published in Acta Biomaterialia, a solution to this problem could come from seaweed — or more precisely, from kappa-carrageenan, a type of polymeric carbohydrate produced by certain types of edible seaweed.  Akhilesh K. Gaharwar, PhD, Assistant Professor of Biomedical Engineering at Texas A&M, led a study team who developed and tested an injectable hydrogel nanoengineered from kappa-carrageenan.

The authors combined kappa-carrageenan with clay-based nanoparticles to yield a hydrogel that can be injected into wounds. When the gel solidifies, it both stanches the flow of blood and helps to generate new tissue. The gel performed well in in vitro experiments. The next step will be to test the gel in animal models of wounds.

A New Understanding of Anatomy

A group of scientists collaborating among Mount Sinai Medical Center, NYU, Weill Cornell Medical Center, and the University of Pennsylvania, including Penn Bioengineering secondary faculty member Rebecca Wells, MD, published a paper in Scientific Reports detailing the heretofore unknown extent of the human interstitium and providing a new understanding of these fluid-filled compartments beneath the skin surface. The study used confocal laser endomicroscopy, which can examine structures at depths of 60-70 µm, to look at human hepatobiliary tissue. They found a reticular pattern of fluid-filled sinuses not detected before, which is connected to the lymph nodes and similar to structures found in other organs and organ systems.

On the basis of their findings, the authors suggest that our current understanding of the anatomy might be revised. Much more research is necessary, but they also believe that the fluid-filled spaces might play important roles in cancer metastasis and a number of other disease processes.

Bringing Bioprinting to the Masses

Three-dimensional printing is one of the great innovations of the last decade, and it has transformed numerous fields inside and outside of science. In the health sciences, the ability to manufacture 3D biomaterials holds enormous promise. Unfortunately, the costs of 3D printing remain prohibitive; the available models range between $10,000 and $200,000 in cost, not including the raw materials, software, etc.  However, engineers at Carnegie Mellon University (CMU) might have devised a solution. In a paper published in HardwareX, Adam Feinberg, PhD, Associate Professor of Biomedical Engineering at CMU, and his coauthors describe their development of a syringe-pump large volume extruder (LVE).

Syringe pump extruders, which inject raw material into 3D printers, are already used to print biomaterials. However, achieving cheap, fast, and precise printing of 3D materials is a major technical challenge. The LVE, which is based on open-source hardware and software, significantly increases the size of the extruder without compromising speed, and it can print at sizes as small as 100 µm. The authors estimate that the materials necessary to build their bioprinter would cost less than $500 — orders of magnitude less than current models that are slower and unable to print using large volumes. Their source materials are online here.

People and Places

Missouri dominates this week’s news, with a new program at one institution and a symposium at another. At the University of Missouri, the College of Engineering has announced that it will begin offering an undergraduate program in biomedical engineering in the fall. Ninety miles away at Missouri University of Science and Technology,  a symposium will be held this week — the first to be convened on the topic of biomedical humanities. The event is a collaboration between Missouri S&T’s Center for Science, Technology, and Society and the Center for Biomedical Research.

Colorado State University’s Department of Biomedical Engineering is celebrating its 10th anniversary. In that time, the department has added more than 20 faculty members to its original cohort of 29.
 
Finally, we offer our congratulations to Jelena Kovačević, PhD, who has been named the new dean at NYU’s Tandon School of Engineering. A graduate of Columbia and the University of Belgrade, Dr. Kovačević, who is an electrical engineer with broad interest in biomedical applications, moves to NYU from CMU and is the first-ever female dean of Tandon. Congratulations Jelena!

Week in BioE (April 2, 2018)

Beer Gets a Hand From Bioengineering

beerBeer is among the oldest beverages known to humankind. While we don’t know what the beer that the ancient Egyptians drank tasted like, there’s little question that the trend toward craft brewing over the past generation has resulted in a proliferation of brews with a range of colors and flavors. Beers with a strong flavor of hops are currently popular, resulting in high demand for the plant that bears them. Like many plants, however, the hop plant requires significant water and energy to produce, adding to the burden of global climate change.

Bioengineers from the University of California, Berkeley, might have found a solution to this problem. In an article recently published in Nature Communications, the Berkeley scientists, led by Jay D. Keasling, Ph.D., from the Department of Bioengineering, described how they engineered brewer’s yeast cells using DNA from mint, basil, and yeast to produce the terpenoid that produces the taste of hops. Taste testers found the beer made from the engineered yeast to be hoppier in flavor than two commercial beers.

The authors of the study acknowledge that a true hop flavor is likely subtler than the register of tastes they used to engineer their brewers yeast. That said, they believe their research could serve as a basis for the genetic engineering of plant products for a range of uses. In addition, the amount of saved money could be enormous — currently, the cost of growing an acre of hop plants is nearly $7,000, which is approximately 10 times that of corn.

Wearables Monitor Digestion

We may be getting a much closer look at certain aspects of digestion thanks to two wearable devices developed by engineers on two sides of the country. On the West Coast, bioengineers at the University of California, San Diego, led by Todd P. Coleman, PhD, professor in UCSD’s Department of Bioengineering,  developed a device to monitor the electrical activity of the stomach over a 24-hour period. Unlike other technologies, this approach doesn’t require the user to drink a barium solution or ingest a tiny camera. The device, which they describe in an article in Scientific Reports, consists of a series of wearable sensors based on EKG technology and an event-logging app for computers or mobile devices. In testing, the new device performed comparably to gastric manometry, a ‘gold standard’ in clinical care that requires insertion of a nasogastric tube. The authors believe their device could have use in gastric motility disorders.

Across the country at Tufts, Fiorenzo Omenetto, PhD, Frank C. Doble Professor in the Department of Biomedical Engineering, led a team of scientists in developing a tooth-mounted sensor that can monitor food intake. The device, which measures 4 square millimeters, is described in an article in Advanced Materials. The sensor could replace the much bulkier mouthguards used for such research in the past.

Painless Lupus Testing

Despite being among the more common autoimmune disorders, lupus is difficult to diagnose. Blood tests often do not provide conclusive results. Ultimately, a kidney biopsy is often necessary to confirm the diagnosis, an invasive procedure that can be problematic with sick patients.

Now, a research team at the University of Houston has developed a saliva test that might eliminate the need for kidney biopsy. Chandra Mohan, MD, PhD, Hugh Roy and Lillie Cranz Cullen Endowed Professor of Biomedical Engineering at UH, received an NIH grant to develop a new technology which identifies proteins in the saliva as biomarkers of lupus. An important aspect of the assay is that it can be used to monitor the disease, as well as diagnose it, so the efficacy of medication to treat the disease can be followed without having to obtain multiple kidney biopsies.

Fluid Shear Stress Affects Ovarian Cells

Like most cancers, survival rates for ovarian cancer have gone up in past decades. As with most cancers, early detection remains a key step to extending survival, but a large proportion of ovarian cancers are not diagnosed until they have metastasized to other organs. Therefore, understanding the process by which normal ovarian cells become cancerous and the mechanism underlying their metastasis could improve our ability to predict these cancers and perhaps detect them earlier.

In response to this issue, researchers at Virginia Tech have uncovered part of the mechanism by which ovarian cancer cells metastasize. Led in part by  Rafael V. Davalos, PhD, L. Preston Wade Professor of Biomedical Engineering and Mechanics, the researchers report in PLOS One that fluid-induced shear stress plays a key role. Ovarian cancer causes the accumulation of fluid in the abdomen, called ascites. Using a mouse model, the study authors found that benign ovarian cells actually became malignant, and malignant cells were more likely to metastasize under this stress. This knowledge could go a long way toward developing more effective treatments for ovarian cancer.

People and Places

Two universities have announced they will begin offering degree programs in biomedical sciences. Among three programs added by Loma Linda University in California is one with an emphasis on neuroscience, systems biology, and bioengineering. Enrollment begins in the fall. In Huntington, W.V., Marshall University has added a bachelor’s degree program in BME, also beginning in the fall.

The University of North Texas, near Dallas, broke ground on a new BME building. The college anticipates the building will open for the Fall 2019 semester.

Finally, we are very proud to report that Elsie Effah Kaufmann, PhD, who earned bachelor’s, master’s, and doctoral degrees from Penn Bioengineering, was honored last week at the 44th annual meeting of the National Society of Black Engineers in Pittsburgh, where she received the 2018 Golden Torch Award for International Academic Leadership. Congratulations!

Week in BioE (March 26, 2018)

A New Theory of Robotics?

robotic catRobots have come a long way in the past few decades, but we’re still a long way off from one that can move like animals and humans. To date, programming movement for robots uses instructions to individual mechanical parts to mimic muscle activity. The main challenge is that the number of small, coordinated muscle movements in walking requires an enormous number of instructions to program. In addition, these instructions are often not very good at accommodating for different surfaces or changing landscapes.

 

One way around this issue might be to focus less on “muscles” and more on neurons for creating the instructions of walking. This is the approach being taken in the lab of Francisco Valero-Cuevas, PhD, Professor of Biomedical Engineering at the University of Southern California. A recent feature at Wired magazine details their construction of a robotic cat based on a network of artificial neurons.

 

The USC model uses reinforcement learning, which is a system whereby neurons of the spinal cord form networks on the basis of trial and error, using random firing of neurons until motion is produced. In this way, the need for an algorithm or complicated programming is eliminated. The cat, called Kleo, is a long way off from being able to land on its feet or use a litter box, but it might give us insight into new technologies that will help people with disabilities from spinal cord injury or motor neuron disease.

Less Neuronal Flexibility With Learning

One of the primary tasks of the brain is learning, but there’s still a lot we don’t know about what happens in the brain as learning occurs. Much of the past research examined changes at the level of individual neurons to explain learning. Newer research, however, has indicated that it is more insightful to examine larger populations of neurons during tasks to get a deeper insight into how the brain learns.

 

Using this principle, a team of engineers and scientists collaborating between Carnegie Mellon and the University of Pittsburgh submitted rhesus monkeys to a learning task and obtained neural recordings to determine how the task affected neuron populations. Their study, led by Steven Chase, PhD, and Byron Yu, PhD, both associate professors of biomedical engineering at CMU, was published in Nature Neuroscience. Drs. Matthew Golub and Penn alumnus Aaron Batista were also coauthors.

 

Contrary to previous thinking, the authors found the brain is less flexible during learning tasks. In part, this lack of flexibility explains why certain tasks take a long time to learn. The authors state that it remains unclear whether the brain changes detected occur at the level of the cortex or subcortex, so additional research will be necessary.

Preventing Bad Science

Academic science remains largely an environment of publish or perish, and this pressure on scientists has unfortunately resulted in an increased incidence of academic fraud. One form of fraud is recycling old images from past publications of successful experiments while presenting the results of newer research.

 

Recognizing that data science could be used to detect such episodes of fraud, Konrad Kording, PhD, a Penn Integrates Knowledge (PIK) Professor with appointments in the Departments of Bioengineering and Neuroscience, and his collaborators developed an algorithm that can compare images across journal articles and detect whether images have been repeated across two articles, even if they have been resized, rotated, or cropped. They describe their technique in a paper recently published on the BioRxiv preprint server. Among the next moves the authors are considering is licensing the algorithm to academic publishers, with the caveat that the possibility of false positive accusations has not been eliminated.

People and Places

Congratulations go to Judy Cezeaux, PhD, who has been named Dean of the Arkansas Tech University College of Engineering and Applied Sciences. A biomedical engineer with degrees from Carnegie-Mellon and Rensselaer Polytechnic Institute, Dr. Cezeaux was most recently chair of the Department of Biomedical Engineering at Western New England University.