Pitt | Swanson Engineering

The Department of Bioengineering combines hands-on experience with the solid fundamentals that students need to advance themselves in research, medicine, and industry. The Department has a long-standing and unique relationship with the University of Pittsburgh Medical Center and other academic departments at the University of Pittsburgh as well as neighboring Carnegie Mellon University. Our faculty are shared with these organizations, offering our graduate and undergraduate students access to state-of-the-art facilities and a wide array of research opportunities. We currently have 187 graduate students who are advised by some 100 different faculty advisers, pursuing graduate research across 17 Departments and five Schools. Our undergraduate class-size of approximately 50 students per year ensures close student-faculty interactions in the classroom and the laboratory.

The main engineering building is located next to the Medical Center in Oakland, an elegant university neighborhood with museums, parks, and great restaurants. Beautiful new facilities have also been built, a short shuttle ride from the main campus, along the Monongahela River, replacing the steel mills that once were there. Our department is growing rapidly, both in numbers of students and faculty, and in the funding and diversity of our research. The Pittsburgh bioengineering community is a vibrant and stimulating alliance of diverse components for which our department forms an essential and central connection.

Jan
22
2020

Researchers Regrow Damaged Nerves with Polymer and Protein

Bioengineering

Reposted with permission from UPMC. Click here to view the original press release. PITTSBURGH, Jan. 22, 2020 –University of Pittsburgh School of Medicine researchers have created a biodegradable nerve guide — a polymer tube — filled with growth-promoting protein that can regenerate long sections of damaged nerves, without the need for transplanting stem cells or a donor nerve. So far, the technology has been tested in monkeys, and the results of those experiments appeared today in Science Translational Medicine. “We’re the first to show a nerve guide without any cells was able to bridge a large, 2-inch gap between the nerve stump and its target muscle,” said senior author Kacey Marra, Ph.D., professor of plastic surgery at Pitt and core faculty at the McGowan Institute for Regenerative Medicine. “Our guide was comparable to, and in some ways better than, a nerve graft.” Half of wounded American soldiers return home with injuries to their arms and legs, which aren’t well protected by body armor, often resulting in damaged nerves and disability. Among civilians, car crashes, machinery accidents, cancer treatment, diabetes and even birth trauma can cause significant nerve damage, affecting more than 20 million Americans. Peripheral nerves can regrow up to a third of an inch on their own, but if the damaged section is longer than that, the nerve can’t find its target. Often, the disoriented nerve gets knotted into a painful ball called a neuroma. The most common treatment for longer segments of nerve damage is to remove a skinny sensory nerve at the back of the leg — which causes numbness in the leg and other complications, but has the least chance of being missed — chop it into thirds, bundle the pieces together and then sew them to the end of the damaged motor nerve, usually in the arm. But only about 40 to 60% of the motor function typically returns. “It’s like you’re replacing a piece of linguini with a bundle of angel hair pasta,” Marra said. “It just doesn’t work as well.” Marra’s nerve guide returned about 80% of fine motor control in the thumbs of four monkeys, each with a 2-inch nerve gap in the forearm. The guide is made of the same material as dissolvable sutures and peppered with a growth-promoting protein — the same one delivered to the brain in a recent Parkinson’s trial — which releases slowly over the course of months. The experiment had two controls: an empty polymer tube and a nerve graft. Since monkeys’ legs are relatively short, the usual clinical procedure of removing and dicing a leg nerve wouldn’t work. So, the scientists removed a 2-inch segment of nerve from the forearm, flipped it around and sewed it into place, replacing linguini with linguini, and setting a high bar for the nerve guide to match. Functional recovery was just as good with Marra’s guide as it was with this best-case-scenario graft, and the guide outperformed the graft when it came to restoring nerve conduction and replenishing Schwann cells — the insulating layer around nerves that boosts electrical signals and supports regeneration. In both scenarios, it took a year for the nerve to regrow. The empty guide performed significantly worse all around. With these promising results in monkeys, Marra wants to bring her nerve guide to human patients. She’s working with the Food and Drug Administration (FDA) on a first-in-human clinical trial and spinning out a startup company, AxoMax Technologies Inc. “There are no hollow tubes on the market that are approved by the FDA for nerve gaps greater than an inch. Once you get past that, no off-the-shelf tube has been shown to work,” Marra said. “That’s what’s amazing here.” Additional authors on the study include Neil Fadia, Jacqueline Bliley, Gabriella DiBernardo, Donald Crammond, Ph.D., Benjamin Schilling, Wesley Sivak, M.D., Ph.D., Alexander Spiess, M.D., Kia Washington, M.D., Matthias Waldner, M.D., Liao Han Tsung, Ph.D., Isaac James, M.D., Danielle Minteer, Ph.D., Casey Tompkins-Rhoades, Deok-Yeol Kim, Riccardo Schweizer, M.D., Debra Bourne, M.D., Adam Cottrill, George Panagis, Asher Schusterman, M.D., Francesco Egro, M.D., Insiyah Campwala, Tyler Simpson, M.S., Douglas Weber, Ph.D., Trent Gause, M.D., Jack Brooker, Tvisha Josyula, Astrid Guevara, Alexander Repko and Christopher Mahoney, all of Pitt. This study was funded by the Armed Forces Institute of Regenerative Medicine (award number W81XWH-14-2-0003). MedGenesis Therapeutix Inc. supplied the growth-promoting protein. Axomax Technologies was formed after the experiments were completed. For additional multimedia, contact Erin Hare at HareE@upmc.edu or 412-738-1097. #  #  # Video credit: UPMC.

Jan
22
2020

Impacting human life now

Bioengineering, Student Profiles

Reposted with permission from the University of Pittsburgh Center for Research Computing. Click here to read the original story. Two images of MRI brain scans are displayed side-by-side on a poster in the Radiofrequency Research Facility in the basement of BST 3, one image marked 3T and one 7T. On the 7T image the hippocampus region of the brain displays a tracing of vessels not visible on the 3T image. “You can clearly see a microstructure in the 7T scan that doesn’t appear in the 3T scan,”  post-doc Tales Santini points out. “That kind of detail is what our scanner system offers.” That scanner is one of the most powerful MRI devices in the world – designated 7T  for 7 Tesla, a measure of the strength of an electromagnetic field (by comparison, Earth’s magnetic field is about 0.00065 T and a refrigerator magnet 0.01 T). MRI scanners in use are primarily 1.5 and 3 Tesla. The increased power of the 7 Tesla scanner reveals details not visible in typical MRI machines. With a resolution up to 180 microns – a micron is a millionth of a meter – the 7 Tesla can identify problems much earlier than existing scanners. 7 Tesla is particularly effective in early detection of brain issues implicated in diseases associated with aging, such as Alzheimer’s and late life depression, diseases which are a focus of the Radiofrequency Research Facility and the 7 Tesla Bioengineering Research program, directed by Tamer Ibrahim, professor of bioengineering, radiology, and psychiatry. The increased frequency of the 7 Tesla represents challenges. If the electromagnetic waves do not enter the skull evenly in a uniform pattern, heat concentrates in individual areas of the brain, considerably raising their temperatures. The maximum possible heating allowed by the U.S.. Food and Drug Administration is one degree centigrade. The lab is currently developing technology to smooth those electromagnetic waves using an array of 70 intricate radiofrequency antennas surrounding the head and neck, dubbed the Tic-Tac-Toe antenna owing to a nine-square grid marked with X’s and O’s displayed on the array’s housing. The team uses the Center for Research Computing to simulate hundreds of thousands of possible configurations of the antennas to create the most uniform possible waves. “The wavelength of tissue is short, about 12 centimeters at 7 Tesla, while the human head is electrically large, about 20 cm front to back,” explains Ibrahim. “We must create a relatively homogenous magnetic field to image a head that is about twice the wavelength of the 7 Tesla in tissue. This is extremely challenging. Without a uniform field, the image quality and usefulness will significantly degrade, and the electrical field can localize and heat the tissue.” Engineer Anthony Defranco, Tamer Ibrahim, and post-doc Tales Santini. Santini is holding the housing of the Tic-Tac-Toe antenna. Now the computational problem. Hundreds of thousands of configurations of the Tic-Tac-Toe antennas must be modeled to optimize that balance of uniform imaging while minimizing the danger of heating before any testing. Each of the 70 antennas is simulated in the presence of the other 69 antennas, the electromagnetic fields from these simulations are combined – potentially in hundreds of millions of different ways - to form the most even, yet safe, magnetic field distribution.  “We use CRC to do the simulation and optimization of the coils, but also in processing human imaging data,” Santini explained. The 7 Tesla scanner and Tic-Tac-Toe antennas are being heavily used in clinical studies. Ibrahim estimates that his team of 12 PhD students, several MS and BS students, two engineering staff, and two post-docs has performed 4,000 human head and neck scans between 2017 and 2024 looking at blood flow, cerebral spinal fluid, small vessels and microstructures in the hippocampus and other brain regions, all of which correlate with diseases like Alzheimer’s. The research is not limited to conditions associated with aging but includes major depressive disorder, schizophrenia, sickle cell, mild cognitive impairment, normal aging, late-life depression, dementia, psychosis, neurocognitive disparities, and linking personality to health, among others. The Tic-Tac-Toe radiofrequency coil system has achieved breakthrough results in terms of image quality and consistency at 7 Tesla. The new capabilities are stimulating significant translational and collaborative research.  Through extensive collaborations with the Alzheimer Disease Research Center and the  Pitt departments of Psychiatry, Medicine, Epidemiology, Neurology, Psychology, and Anesthesiology, Ibrahim’s lab has attracted close to $40 million in grant funding over the last four years, including 17 National Institutes of Health grants. A recent NIH award of over $3.75 million funds research by Ibrahim and collaborators in the Department of Psychiatry into developing new 7 Tesla technology to investigate relationships between preclinical Alzheimer’s disease and small vessel and cerebrospinal fluid conditions. Ibrahim is also central to an initiative of the departments of Bioengineering and Psychiatry to create a multidisciplinary training program for pre-doc bioengineering students to participate in mental health research, an initiative that recently received $1.1 million from the NIH. “This is an exciting time,” says Ibrahim. “Our engineering innovations are being used on real patient studies. We’re not making something that just could be used some time in the future. We are impacting human life now.”

Jan
9
2020

Advancing Neural Stimulation: Kozai Designs a Wireless, Light-Activated Electrode

Bioengineering

PITTSBURGH (Jan. 9, 2020) … Neural stimulation is a pioneering technology that can be used to recover function and improve the quality of life for individuals who suffer from brain injury or disease. It serves an integral role in modern neuroscience research and human neuroprosthetics, including advancements in prosthetic limbs and brain-computer interfaces. A challenge that remains with this technology is achieving long-term and precise stimulation of a specific group of neurons. Takashi D-Y Kozai, assistant professor of bioengineering at the University of Pittsburgh, recently received a $1,652,844 award from the National Institutes of Health (1R01NS105691-01A1) to develop an innovative solution to address these limitations. “Implantation of these devices causes a reactive tissue response which degrades the functional performance over time, thus limiting device capabilities,” Kozai explained. “Current electrical stimulation implants are tethered to the skull, which leads to mechanical strain in the tissue, and in turn, causes chronic inflammation and increases the possibility of an infection.” Kozai, who leads the Bio-Integrating Optoelectric Neural Interface Cybernetics Lab in the Swanson School of Engineering, will use the NIH award to develop a wireless in vivo stimulation technology that will enable precise neural circuit probing while minimizing tissue damage. In this design, the electrode will be implanted in the brain and activated by light - via the photoelectric effect - with a far-red or infrared laser source, which can sit outside of the brain. “This use of photostimulation removes the mechanical requirements necessary in traditional microstimulation technology and improves spatial selectivity of activated neurons for stable, long-term electrical stimulation,” Kozai said. His group found that photostimulation drives a more localized population of neurons when compared to electrical stimulation under similar conditions. When used, the activated cells were closer to the electrode, which indicates increased spatial precision. The proposed technology will be smaller than traditional photovoltaic devices but larger than nanoparticles to improve device longevity. “With this project, we hope to develop advanced neural probes that are capable of activating specific neurons for long periods of time and with great precision,” Kozai said. “This technology could significantly impact neuroscience research and ultimately the treatment of neurological injury and disease in humans.” ###

Jan
6
2020

Take heart: Pitt study reveals how relaxin targets cardiovascular disease

Bioengineering, Student Profiles

PITTSBURGH (Jan. 6, 2020) … As a healthy heart ages, it becomes more susceptible to cardiovascular diseases. Though researchers have discovered that relaxin, an insulin-like hormone, suppresses atrial fibrillation (AF), inflammation, and fibrosis in aged rats, the underlying mechanisms of these benefits are still unknown. In a recent Scientific Reports paper, University of Pittsburgh graduate student Brian Martin discusses how relaxin interacts with the body’s signaling processes to produce a fundamental mechanism that may have great therapeutic potential. The study, “Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling” (DOI: 10.1038/s41598-019-53867-y) was led by Guy Salama, professor of medicine at Pitt, and Brian Martin, a graduate student researcher from the Swanson School of Engineering’s Department of Bioengineering. “Relaxin is a reproductive hormone discovered in the early 20th century that has been shown to suppress cardiovascular disease symptoms,” said Martin. “In this paper, we show that relaxin treatment reverses electrical remodeling in animal models by activating canonical Wnt signaling - a discovery that reveals a fundamental underlying mechanism behind relaxin’s benefits.” A better understanding of how relaxin interacts with the body may improve its efficacy as a therapy to treat cardiovascular disease in humans. As the U.S. population ages, the rates of these age-associated diseases are expected to rise, requiring better treatment for this leading cause of death. According to a report from the American Heart Association, the total direct medical costs of cardiovascular disease are projected to increase to $749 billion in 2035. “A common problem in age-associated cardiovascular disease is altered electrical signaling required for proper heart contraction,” Martin explained. “When ions in the heart and their associated channels to enter or exit the heart are disrupted, complications occur.” “Natural, healthy aging has been shown to be accompanied by changes in structure and function,” Salama added. “For example, aged cardiomyocytes start to express embryonic contractile proteins and fewer voltage-gated Na+ channels by unknown mechanisms. The reversal of some aspects of the aging process by relaxin is mediated by the reactivation of Wnt canonical signaling which may partly explain mechanisms of the aging process.” The group’s study found that relaxin upregulated the prominent sodium channel, Nav1.5, in cells of heart tissue via a mechanism inhibited by the Wnt pathway inhibitor Dickkopf-1. “Wnt signaling is thought to be active primarily in the developing heart and inactive later in life,” Martin said. “However, we show that relaxin can reactivate Wnt signaling in a beneficial way to increase Nav1.5.” Increased Nav1.5 is associated with better electrical signaling in the heart may reduce susceptibility to cardiac rhythm disorders. “Further, we show that relaxin can also reverse the age-associated reduction in cell adhesion molecules and cell-cell communication proteins,” he continued. “In summary, relaxin appears to reverse problematic reductions or pathological reorganization of vital cardiac signaling proteins.” While these data provide new insight into relaxin’s mechanisms of action, further work is needed to understand the precise steps required for relaxin to alter Wnt signaling and if steps can be taken to directly alter Wnt signaling to provide its beneficial effects. ### Image caption: “Left ventricular tissue sections (7-µm thick) from aged rat hearts (24 months old) were labeled with the nuclear stain (DAPI-blue) and an antibody against β-catenin (green). Rats were treated with Relaxin (0.4 mg/kg/day for 2-weeks) (left panel) or with the control vehicle (sodium acetate) (right panel) and the tissue sections were imaged by confocal microscopy (600X magnification). Relaxin treatment (left) produced a marked positive remodeling of aged ventricles with a reduction of cell hypertrophy, improved organization of myofibrils and cell membrane compared to untreated, control aged hearts (right).” Credit: Dr. Guillermo Romero.

Dec
17
2019

Three Bioengineering Graduate Students Receive American Heart Association Fellowships

Bioengineering, Student Profiles

PITTSBURGH (Dec. 17, 2019) … Three students from the University of Pittsburgh Department of Bioengineering received 2020 American Heart Association Predoctoral Fellowships, which provides up to two years of project support for aspiring academic and health professionals. “The Swanson School of Engineering has placed an emphasis on encouraging and helping  PhD students to compete for the prestigious national predoctoral fellowships because this effort is highly relevant from both educational and professional development perspectives,” said Sanjeev G. Shroff, Distinguished Professor and Gerald E. McGinnis Chair of Bioengineering. “This is the largest number of AHA fellowships the Department of Bioengineering PhD students have received in a single year, and I am proud of the research accomplishments of each of these students. I look forward to seeing the continued growth of these students as independent investigators.” Ali Behrangzade (PI: Jonathan Vande Geest) Behrangzade works in the Soft Tissue Biomechanics Laboratory (STBL) where they have extensive experience in design, optimization, manufacturing and in vivo evaluation of tissue-engineered vascular grafts (TEVGs). These grafts are used in a coronary artery bypass procedure which is required for most patients with coronary artery disease (CAD). The surgery requires autologous vessels, which are blood vessels harvested from the patient’s own body, however, these vessels are not always suitable because of prior harvesting or pre-existing vascular disease. One of the major causes of graft failure in reconstructive CABG surgery is intimal hyperplasia (IH). This pathological condition is characterized by the thickening of the inner layer of a blood vessel due to an undesired mechanical and biological environment. As part of Behrangzade’s TEVG project, he will create an optimized TEVG-patch system and surgically connect it to an artery (anastomose) to evaluate the performance in an animal model. “Our approach will be to use a combined experimental and computational strategy to design, fabricate and assess the ability of a mechanically and geometrically optimized biopolymer TEVG-patch to maintain the homeostatic biomechanical environment (solid and fluid) in an end-to-side anastomosis,” said Behrangzade “We hypothesize that this will reduce the incidence of IH and therefore improve the patency rate of bypass procedures. The optimized graft-patch will then be fabricated and implanted into a rabbit carotid artery end-to-side anastomosis model to assess the function of the graft-patch system in vivo. The results of this study will potentially make significant improvements in the outcome of CABG surgery.” Soroosh Sanatkhani (PI: Sanjeev Shroff and Prahlad Menon) Sanatkhani is involved in multiple cardiovascular research projects under the supervision of Sanjeev Shroff, Distinguished Professor and Gerald E. McGinnis Chair of Bioengineering, and Prahlad Menon, adjunct assistant professor of bioengineering. His primary research is focused on hemodynamics indices and shape-based models of the left atrial appendage (LAA) of the heart to enhance stroke prediction in atrial fibrillation (AF). “In this study I plan to create two novel, patient-specific indices to improve the prediction of stroke in AF patients,” said Sanatkhani. “The first index is a hemodynamics-based calculation of residence time in LAA, which represents the probability of clot formation in the LAA and consequently a metric for stroke risk. The second index will quantify the LAA appearance (shape), which will help us correlate the probability of stroke with geometrical features of LAA” According to Sanatkhani, this project should result in a new and significantly improved method to predict stroke risk in patients with atrial fibrillation, which will enhance the clinical management in these patients Danial Sharifi Kia (PI: Marc Simon and Kang Kim) Sharifi Kia’s research is focused on right ventricular biomechanics in pulmonary hypertension, under the supervision of Marc Simon and Kang Kim, associate professors of medicine and bioengineering. The heart-lung system in the human body handles carrying blood from the heart to the lungs. Pulmonary hypertension (PH) is a disease that results from the arteries in the heart-lung system getting restricted, which leads to high blood pressure in these arteries and the heart. As a result, the heart needs to work harder to pump blood, eventually leading to heart failure - the main cause of death for nearly 70 percent of PH patients. Despite many developments, to date, lung transplantation remains the only cure for PH and current imaging techniques are often not able to effectively track the structural alterations in the heart of PH patients. “We are currently working on a newly developed drug called Sacubitril/Valsartan (Sac/Val) that has shown great potential for heart failure treatment,” said Sharifi Kia. “We test the effectiveness of treatment with this drug in PH by using an animal model of PH in rats. Furthermore, we will also be developing a novel high-frequency ultrasound imaging technology to visualize the fiber architecture of the heart of PH patients with enough resolution. "Since Sac/Val is already FDA-approved, results of this study can be quickly translated into the clinic and provide a treatment option for PH patients,” he continued. “Additionally, the proposed imaging technology may improve monitoring of structural changes in the heart of PH patients.” ###

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