University of Pittsburgh Faculty Elected Senior Members of the National Academy of Inventors

Bioengineering

Reposted from the Innovation Institute. Click here to view the original story. The National Academy of Inventors (NAI) has selected three University of Pittsburgh professors among 61 academic inventors for the 2021 class of NAI Senior Members. They are: Bryan Brown, Associate Professor, Department of Bioengineering Michael Lotze, Professor, Department of Surgery Kacey Marra, Professor, Departments of Plastic Surgery NAI Senior Members are active faculty, scientists and administrators from NAI Member Institutions who have demonstrated remarkable innovation producing technologies that have brought, or aspire to bring, real impact on the welfare of society. They also have growing success in patents, licensing and commercialization. “I want to congratulate Drs. Brown, Lotze and Marra on joining an exclusive society of academic inventors,” said Evan Facher, Vice Chancellor for Innovation and Entrepreneurship at the University of Pittsburgh and Director of the Innovation Institute. “They all have demonstrated exceptional commitment to achieving impact for their research through commercial translation. Importantly, they have years of innovating ahead of them. We look forward to helping them bring more of those discoveries to market where they can make a difference in people’s lives.” Two of the new NAI Senior Members are developing solutions for treating large gap nerve injuries. Bryan Brown has been issued eight patents, with several more pending. He launched a startup company in 2017, Renerva, from his lab at the McGowan Institute for Regenerative Medicine. Dr. Brown leveraged more than $300,000 in commercialization gap funding from within the university while working one-on-one with an entrepreneur in residence from Pitt’s Innovation Institute, Lorenzo Soletti, who has become Renerva’s CEO. Since launching, the company has raised more than $1 million in investment capital, while also securing more than $3 million in grants from the Department of Defense, the National Institutes of Health and the National Science Foundation, to advance its preclinical programs. Kacey Marra was inspired to pursue commercial translation after receiving funding from the Department of Defense for her research and meeting soldiers who had received significant nerve damage from wounds suffered in combat. Since arriving at Pitt in 2002, she has submitted 20 invention disclosures to the Pitt Innovation Institute, which ties her for most among female faculty members. She has been issued 3 patents with many more pending. Dr. Marra and her lab have demonstrated in animal studies the ability to restore up to 80 percent of nerve function in large-gap injuries through the application of a biodegradable tube containing a time-released protein growth factor. With her research showing continuing promise, Dr. Marra launched her own company, Nerve Repair Technologies, in 2018. Michael Lotze is a pioneer in the cancer immunotherapy field and is the co-inventor of multiple patents in dendritic cell vaccines, antigen discovery, and tumor infiltrating lymphocyte therapy. He previously held leadership roles in industry as the chief scientific officer of Iovance Biotherapeutics, which is presently conducting four Phase 2 clinical trials for treatment of patients with metastatic melanoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer (NSCLC) and cervical cancer. Earlier he had been vice president of research at GlaxoSmithKline. He was also senior advisor for the Immune Transplant and Therapy Center, a partnership between Pitt and UPMC. This latest class of NAI Senior Members represents 36 research universities, government, and non-profit research institutes. They are named inventors on over 617 issued U.S. patents. “With the NAI Senior Member award distinction, we are recognizing innovators who are rising stars in their fields and the innovative ecosystems that support their work,” said Paul R. Sanberg, NAI President. Following a nomination for NAI Senior Member, individuals undergo a rigorous selection process by the NAI Advisory Committee, which is composed of elected NAI members and other professionals considered pioneers in their respective field. Senior Members are elected biannually, and nominations are accepted on a rolling basis. Nominations are currently being accepted for the next Senior Member class. A full list of NAI Senior Members is available on the NAI website.

Feb

16

2021

Using a Machine Model to Predict Risk of Human Aneurysms

Bioengineering

PITTSBURGH (Feb. 16, 2020) ... An abdominal aortic aneurysm (AAA) can be a ticking time bomb if undiscovered in time. However, researchers at the University of Pittsburgh are developing a new model to better predict at-risk patients. And the tools they are using apply mechanical testing to the human body - which is itself a complex machine. An AAA occurs when the aorta weakens and begins to irreversibly dilate, like a slowly inflating balloon. If left untreated, the risk of rupture increases and has a 90 percent rate of mortality, making AAA the 15th leading cause of death in the United States with more than 15,000 deaths reported annually. Once diagnosed, clinicians must determine whether the aorta requires surgery, using the AAA diameter to decide if an aneurysm is clinically relevant. A diameter 5.5 centimeters or larger typically calls for surgical intervention, barring other contraindications, but this one-size-fits-all approach misses nearly 25 percent of patients who experience a rupture at a smaller size. Pitt bioengineer David A. Vorp received an award from the National Institutes of Health to track the natural evolution of small AAA and develop a predictive model to improve patient prognosis. His Vascular Bioengineering Lab at the university’s Swanson School of Engineering is focused on finding novel diagnoses and treatments for these silent killers. “It’s a ticking time bomb,” explained Timothy Chung, a post-doctoral associate in Vorp’s lab. “Once you diagnose an abdominal aortic aneurysm, you don’t know when or if it’s going to rupture. “Imagine you’re blowing up a balloon, and it pops. This event involves the mechanics and forces that are interacting with the wall of the balloon,” continued Chung, who will help lead the project. “We’re interested in the biomechanics of why elevated pressure or a weakening of the aneurysm wall might lead to rupture or accelerated growth.” The research team hopes that CT scans and other data from a rare, longitudinal clinical trial (“Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial”) will help them identify the risks of elevated growth rate or eventual rupture. Vorp’s lab group will create 3D geometric reconstructions and perform biomechanical simulations on patient datasets at each imaging scan interval (every six months) to learn how small AAA progresses over time. They will then use the scans and unique software tools from their lab to perform shape analyses that will determine which geometries may lead to poor patient outcomes. “Currently, clinicians are simply applying a one-dimensional shape analysis, using diameter as a threshold for clinical intervention,” said Chung. “The tools developed in the Vascular Bioengineering Lab can help us extract more than one-dimensional measurements. They allow us to create two- and three-dimensional shape indices derived from image-based surface reconstructions, allowing for a more robust analysis.” The team will then feed data from the shape analysis and biomechanical simulations to train a machine learning algorithm to classify different types of aneurysm outcomes. This will be used to develop a predictive model that can help guide clinicians and determine the need for surgical intervention. “Early in my career, the advent of finite element analysis – a computational method to predict mechanical wall stress distribution in complex shapes both biological and human-made – provided a game-changing tool to better understand the role of biomechanics in AAA disease,” said Vorp, Associate Dean for Research and John A. Swanson Professor of Bioengineering. “Now, machine learning technologies can not only help us better understand the combination of factors that lead toward rupture or clinical intervention, but also package that knowledge into a true, personalized health tool for those afflicted with this potentially lethal condition.” # # #

Feb

15

2021

UPMC/Pitt Orthopaedic Robotics Laboratory Experts Study ACL Injury Features with Three-Dimensional Statistical Shape Modeling

Bioengineering

Reposted from UPMC Physician Resources. Click here to view the original article. A study to investigate tibiofemoral bony morphology features associated with ACL injury and sex utilizing three-dimensional statistical shape modeling was conducted by: Sene Polamalu, BSThird-year Bioengineering PhD Student Researcher Orthopaedic Robotics Laboratory, University of Pittsburgh Volker Musahl, MDBlue Cross of Western Pennsylvania ProfessorChief UPMC Sports Medicine Medical DirectorProfessor, University of Pittsburgh Departments of Orthopaedic Surgery, Bioengineering, and Clinical Translational Science Institute Richard Debski, PhDWilliam Kepler Whiteford Faculty FellowCo-Director, Orthopaedic Robotics LaboratoryProfessor, University of Pittsburgh Departments of Bioengineering and Orthopaedic Surgery In the study, statistical shape modeling was employed to assess three-dimensional (3D) bony morphology between: Distal femurs and proximal tibiae of anterior cruciate ligament (ACL) injured knees. The contralateral uninjured knees of ACL injured subjects. Knees with no history of injury. Surface models were created by segmenting bone from bilateral computed-tomography scans of: 20 subjects of their ACL injured knees and non-injured contralateral knees. 20 knees of control subjects with no history of a knee injury. Correspondence particles were placed on each surface, and a principal component analysis determined modes of variation in the positions of the correspondence particles describing anatomical variation. ANOVAs assessed the statistical differences of 3D bony morphological features with main effects of injury state and sex. ACL injured knees were determined to have a more lateral femoral mechanical axis and a greater angle between the long axis and condylar axis of the femur. A smaller anterior-posterior dimension of the lateral tibial plateau was also associated with ACL injured knees. Results of this study demonstrate that there are more bony morphological features predisposing individuals for ACL injury than previously established. These bony morphological parameters may cause greater internal and valgus torques increasing stresses in the ACL. No differences were determined between the ACL injured knees and their uninjured contralateral knees demonstrating that knees of ACL injured individuals are at similar risk for injury. Further understanding of the effect of bony morphology on the risk for ACL injury could improve individualized ACL injury treatment and prevention. Read more about this study on PubMed.

Feb

8

2021

Helping Translational Research Meet the Needs of Older Adults

Bioengineering

PITTSBURGH (Feb. 8, 2021) … In this digital age, where the internet accelerates technological development, there has been a surge of scientific innovation designed to improve the quality of life for patients in need. However, there are physical, cognitive, and sensory issues that are often overlooked during the process, resulting in poor design for a particular user group –adults aged 65 and older. According to the U.S. Census Bureau, this group will comprise more than 20 percent of the U.S. population starting in 2030. Highlighting the importance for safety and efficacy, the U.S. Federal Drug Administration has made incorporating human factors a priority for device approval which can significantly impact the road to commercialization, leaving many researchers stuck in the design phase. Unfortunately, many of these technologies and interventions struggle to advance to commercialization. A new program at the University of Pittsburgh hopes to help investigators navigate this common roadblock. Funded by the National Institutes of Health, Professor Mark Redfern will establish a Human Factors of Aging program at Pitt to inform, support, and advance the translation of research focused on improving the lives of older adults. “There are a huge number of factors to take into consideration when designing for older adults, and with this program, we hope to educate our investigators and innovators and create a collaborative community to help translate research across the University,” said Redfern, professor of bioengineering at Pitt’s Swanson School of Engineering. In 2018, Redfern spent part of a sabbatical at the FDA to learn more about how human factors are evaluated. He will use this knowledge along with his 20 years of experience in human factors and aging research to help investigators at Pitt advance their work. “Many changes occur with age that should be considered in design. For example, vision changes can include loss of acuity, contrast sensitivity, depth perception and field of view, making a display more difficult to see. Physical changes such as reduced strength and struggles with balance can also occur, making devices designed for mobility perhaps more difficult to use,” he explained. “On the cognitive side, memory and attention may be an issue so developers must design a product understanding these limitations. “My goal is to help make our investigators aware of these factors that they may not have otherwise considered as they think of translating their research into action.” Redfern will use this K07 award to educate investigators, their post-doctoral researchers and graduate students. He currently teaches a course on Human Factors Engineering of Medical Devices for engineering students, but now wants to develop courses and workshops more broadly for the University community. He will also use the Human Factors Laboratory within the Human Movement and Balance Laboratory to help them develop and test prototypes. As part of the program, Redfern hopes to bring together a network of people with a vested interest in aging research – from engineers and clinicians to companies and University centers. “One of the most exciting things is our partnership with Pitt’s Alzheimer's Disease Research Center,” Redfern said. “Their knowledge about the impact of cognitive decline and Alzheimer’s disease on functional capabilities will be integrated into the program to improve design for older adults with these challenges. This collaboration will give program participants a practical and robust education on the human factors of aging.” Ultimately, he hopes that this program will advance the world-class translational research at Pitt and have a positive impact on the lives of older adults. If successful, he will develop resources to extend the program nationally. # # #

Feb

4

2021

Alpha Chi Continues the Conversation on Racial Equality

Bioengineering, Student Profiles

Race relations and social justice have been in the spotlight in recent years, calling on individuals to devote energy toward creating a more equitable future for everyone. Allies have been encouraged to consider their privilege and educate themselves on the deep-rooted issues that contribute to racism in the United States. This self-reflection and realization, however, has left some overwhelmed or uncertain about how they can personally effect change. Working together and learning from one another may lend to a richer understanding of these issues, and Alpha Chi National College Honor Society will host a forum to help its members and greater community start the process. On Saturday, Feb. 6, in line with the start of Black History Month, they hope to facilitate an engaging conversation about “Personal Perspectives on Race, Privilege, and Responsibility.” “The seminar continues the current dialogue of fighting for social justice,” said Ande Marini, a bioengineering PhD student at the University of Pittsburgh Swanson School of Engineering. “Personally, I love learning about other people’s cultures and learning how people’s experiences have shaped their perspectives. “Learning about the hardships others have faced and how we can help those individuals is crucial to growing as a society. We need to have this dialogue to better understand each other’s perspectives, and having difficult conversations provides new avenues for growth and understanding.” When Alpha Chi called for nominations for the panel, Marini decided to nominate Steven Abramowitch, associate professor of bioengineering at Pitt. Abramowitch has contributed diversity and inclusion in the Swanson School through programs such as PITT STRIVE, the Global Engineering Preparedness Scholarship (GEPS), Engineering Design for Social Change: South Africa, and CampBioE. "I was honored to be nominated by Ande and to be selected for this panel,” Abramowitch said. “Our lives have been especially chaotic over the last year; thus, it is wonderful that Alpha Chi is using this time to help us do some reflection and encourage us to think beyond ourselves again." He will participate as one of three panelists in the seminar: Steven Abramowitch, associate professor of bioengineering at the University of Pittsburgh Swanson School of Engineering, will focus on positive actions students can take to address diversity issues. Dwonna Goldstone, associate history professor and director of the African American Studies program at Texas State University in San Marcos, Texas, will focus on her experience in helping people with difficult conversations about race. Justine Pas, associate professor of English and associate dean in the School of Humanities at Lindenwood University in St. Charles, Missouri, will share personal experiences and discuss the concept of white privilege. The seminar will be hosted and moderated by Lara Noah, executive director of Alpha Chi. “This panel is the second event in the first series of its kind as an educational initiative from Alpha Chi's national headquarters,” she said. “Other than programming during our annual national convention, educational events like these are typically planned and conducted at the local chapter level. I’m very much looking forward to our conversation on Saturday and appreciate Dr. Abramowitch’s participation.” “… and Justice for All” is the theme for the organization’s 2021 national conference, and this event was planned to help raise awareness of these issues among the Alpha Chi community. “Sharing these topics with the collegiate generation, both undergraduate and graduate, is important and can open their eyes to new perspectives,” Marini added. “By impacting this generation, we are laying a foundation built upon understanding, love, and acceptance for our future leaders.” About Alpha Chi Alpha Chi National College Honor Society was founded in 1922 to recognize and promote academic excellence among college and university students of all disciplines, to encourage a spirit of service and leadership, and to nurture the elements of character that make scholarship effective for good. Alpha Chi is a member in good standing with the Association of College Honor Societies. You can learn more about Alpha Chi at AlphaChiHonor.org.

Feb

3

2021

Bioengineering Names Linggang Luo its 2020 Wesley C. Pickard Fellow

Bioengineering

PITTSBURGH (Feb. 3, 2021) … Linggang Luo, a bioengineering graduate student at the University of Pittsburgh, was named the 2020 Wesley C. Pickard Fellow by the Department of Bioengineering. Recipients of this award are selected by the department chair and chosen based on academic merit. Luo received his bachelor’s degree in bioengineering at Harbin Institute of Technology in Weihai, China and his master’s degree in biomedical engineering at Columbia University before joining the graduate program at Pitt’s Swanson School of Engineering. “I chose Pitt’s bioengineering program because it is among the top programs in the United States,” Luo said. “For those who are simultaneously interested in neuroscience and imaging, there are many opportunities, including collaborations between Pitt, UPMC, Carnegie Mellon University and the Center for the Neural Basis of Cognition.” Luo works in the lab of Fang-Cheng (Frank) Yeh, MD, PhD, assistant professor of neurological surgery at Pitt’s School of Medicine, where he studies tractography, a 3D modeling technique that uses magnetic resonance imaging (MRI) data to visualize nerve tracts. Specifically, he looks at how this tool can be used to map structural properties of the brain, such as white matter tracts. “Diffusion MRI has arisen as the only non-invasive way to map white matter bundles and assess their structural integrity in the human brain,” Luo explained. “There is a growing interest in large-scale analysis of diffusion MRI to explore its promising applications in biomedical research as an imaging biomarker of neuropathology. “With fast imaging sequences, diffusion MRI -- particularly its high angular resolution variants -- can be acquired on standard clinical scanners,” he added. “This advancement has gained considerable interest because of its roles in mapping human connectome and potential for accessing neurological disorders.” Improved imaging will allow researchers to gain a better understanding of neural function and may eventually help predict and improve treatment of neurological disorders. “Diffusion MRI is a challenging field with keen competition from top engineers around the world, who are striving to lift technical obstacles for clinical needs,” Dr. Yeh said. “I am thrilled that Linggang has decided to take on this challenge and work side-by-side with me. It is a tough choice, but I believe there is promising potential for him to change health care practice in the future.” After he completes his PhD, Luo plans to pursue a career in academia and lead his own neuroscience research laboratory. “I appreciate this fellowship and the opportunity it has allowed me to advance research in this field,” Luo said. “I hope to make a positive impact that can one day improve the treatment of neurological disorders.” About Wesley C. Pickard: Mr. Pickard is an alumnus of the Swanson School of Engineering and earned his bachelor's degree in mining engineering at Pitt in 1961. He retired from Synergy Inc, a DC based consulting firm as the CFO. Over a period of 33 years, Pickard helped the company grow from five staff members to more than 200 with revenues of approximately $25 million when it was sold in 2005. His support of Pitt includes the establishment of this fellowship, and he was recently inducted into the Cathedral of Learning Society at Pitt—a giving society that honors some of our most generous alumni. In 2010 Mr. Pickard was named the University of Pittsburgh Department of Civil and Environmental Engineering Distinguished Alumnus. He also received the Pitt Volunteer of Excellence Award in 2012 and was named a “Significant Sig” in 2017 by Sigma Chi Fraternity. In 2018 he was selected as the overall honoree representing the entire Swanson School at the 54th annual Distinguished Alumni Banquet.

Jan

27

2021

Hemolung® RAS Used to Treat More than 75 COVID-19 Patients

Covid-19, Bioengineering

Reposted from Business Wire. Click here to view the original press release. PITTSBURGH--(BUSINESS WIRE)--ALung Technologies, Inc., the leading provider of low-flow extracorporeal carbon dioxide removal (ECCO2R) technologies for treating patients with acute respiratory failure, announced that it has now treated more than 75 COVID-19 patients, and that it is experiencing increasing demand for the Hemolung® Respiratory Assist System (RAS) as a result of the current pandemic. The Food and Drug Administration (FDA) granted the Company Emergency Use Authorization (EUA) designation to the Hemolung RAS for the treatment of COVID-19 patients in the second quarter of 2020. The Hemolung is the only ECCO2R device currently granted an EUA for the treatment of COVID-19. “The Hemolung RAS has enabled us to recover patients with COVID pneumonia during the pandemic. In select patients where there is a selective issue with hypercarbic respiratory acidosis while their oxygen requirements have normalized post-Veno-Venous ECMO cannulation, we have utilized Hemolung as a bridge in their recovery. We have noticed that these patients are able to wean off mechanical circulatory support in a gradual manner. Additionally, at a time when there was a shortage of ECMO circuits, our program has relied on utilizing this technology in stabilizing patients with severe hypercarbic respiratory acidosis while providing lung protective ventilation,” stated Dr. Bindu Akkanti, MD, Associate Professor of Medicine, Divisions of Critical Care, Pulmonary and Sleep Medicine, McGovern Medical School, and Director of Heart and Vascular Critical Care, Memorial Hermann - Texas Medical Center. “The Hemolung RAS has given us a new tool during the current pandemic, to safely and easily treat our COVID-19 patients. We were able to rapidly introduce the Hemolung RAS to our staff and start treating patients under Emergency Use Authorization. As a smaller community hospital without an ECMO program, the ease of use of the Hemolung has played a large role in the successful deployment of ECCO2R for the treatment of COVID-19 at Palm Beach Gardens Medical Center,” stated Ribal Darwish, MD, Medical Director Critical Care Medicine, Palm Beach Gardens Medical Center. “We are pleased to be able to assist in this fight against the COVID-19 viral disease by providing the use of the Hemolung RAS as a tool for physicians to be used in conjunction with IMV, by reducing or eliminating the potential of further lung damage caused by high ventilator driving pressures, often referred to as Ventilator Induced Lung Injury (VILI). We are treating COVID-19 patients in greater than 20 hospitals worldwide,” said Mr. Peter M. DeComo, Chairman and CEO of ALung Technologies. In its EUA approval letter to ALung the FDA stated that it believes the Hemolung RAS has the potential to treat lung failure as an adjunct to noninvasive or invasive mechanical ventilation, to reduce hypercapnia and hypercapnic acidosis due to COVID-19, and/or to maintain normalized levels of partial pressure of carbon dioxide(PCO2) and pH in patients suffering from acute, reversible respiratory failure due to COVID-19 for whom ventilation of CO2 cannot be adequately, safely, or tolerably achieved and, in turn, may provide clinical benefit, and that there is no adequate, approved and available alternative to the emergency use of the Hemolung RAS to treat lung failure caused by COVID-19. About ALung Technologies ALung Technologies, Inc. is a privately held Pittsburgh-based developer and manufacturer of innovative lung assist devices. Founded in 1997 as a spin-out of the University of Pittsburgh, ALung has developed the Hemolung RAS as a dialysis-like alternative or supplement to mechanical ventilation. ALung is backed by Philips, UPMC Enterprises, Abiomed, The Accelerator Fund, Allos Ventures, Birchmere Ventures, Blue Tree Ventures, Eagle Ventures, Riverfront Ventures, West Capital Advisors, and other individual investors.For more information about ALung and the Hemolung RAS, visit www.alung.com.For more information on the VENT-AVOID trial, and a list of enrolling sites, please visit clinicaltrials.gov.For more information on the use of the Hemolung RAS for COVID-19 patients, please visit https://www.alung.com/covid-19/covid-19-us/*The Hemolung RAS has not been FDA cleared or approved.*The Hemolung RAS has been authorized for the above emergency use by FDA under an EUA.*This device is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the Hemolung RAS under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb- 3(b)(1), unless the authorization is terminated or revoked sooner.This press release may contain forward-looking statements, which, if not based on historical facts, involve current assumptions and forecasts as well as risks and uncertainties. Our actual results may differ materially from the results or events stated in the forward-looking statements, including, but not limited to, certain events not within the Company’s control. Events that could cause results to differ include failure to meet ongoing developmental and manufacturing timelines, changing GMP requirements, the need for additional capital requirements, risks associated with regulatory approval processes, adverse changes to reimbursement for the Company’s products/services, and delays with respect to market acceptance of new products/services and technologies. Other risks may be detailed from time to time, but the Company does not attempt to revise or update its forward-looking statements even if future experience or changes make it evident that any projected events or results expressed or implied therein will not be realized.

Jan

25

2021

A Microscopic Look at Aneurysm Repair

Bioengineering, MEMS

PITTSBURGH (Jan. 25, 2021) — Hitting a pothole on the road in just the wrong way might create a bulge on the tire, a weakened spot that will almost certainly lead to an eventual flat tire. But what if that tire could immediately begin reknitting its rubber, reinforcing the bulge and preventing it from bursting? That’s exactly what blood vessels can do after an aneurysm forms, according to new research led by the University of Pittsburgh’s Swanson School of Engineering and in partnership with the Mayo Clinic. Aneurysms are abnormal bulges in artery walls that can form in brain arteries. Ruptured brain aneurysms are fatal in almost 50% of cases. The research, recently published in Experimental Mechanics, is the first to show that there are two phases of wall restructuring after an aneurysm forms, the first beginning right away to reinforce the weakened points. “Imagine stretching a rubber tube in a single direction so that it only needs to be reinforced for loads in that direction. However, in an aneurysm, the forces change to be more like those in a spherical balloon, with forces pulling in multiple directions, making it more vulnerable to bursting,” explained Anne Robertson, professor of mechanical engineering and materials science at Pitt, whose lab led the research. “Our study found that blood vessels are capable of adapting after an aneurysm forms. They can restructure their collagen fibers in multiple directions instead of just one, making it better able to handle the new loads without rupturing.” Researchers have known that blood vessels have the ability to change and restructure over time, but this study represents the first observation of a new, primary phase of restructuring that begins immediately. The researchers used a rabbit model developed by David Kallmes of the Mayo Clinic to observe this restructuring in the brain tissue over time. To see this process up close, the researchers partnered with Simon Watkins at Pitt’s Center for Biologic Imaging, taking advantage of the center’s state-of-the-art multiphoton microscopes to image the architecture of the fibers inside the aneurysm wall. “We found that the first phase of restructuring involves laying down an entirely new layer of collagen fibers in two directions to better handle the new load, while the second phase involves remodeling existing layers so their fibers lie in two directions,” explained Chao Sang, who was a primary investigator on this research as part of his doctoral dissertation in Pitt’s Department of Mechanical Engineering and Materials Science “The long-term restructuring is akin to a scar forming after a cut has healed, while this first phase that we observed can be thought of as having a role similar to clotting immediately after the cut—the body’s first response to protect itself,” added Robertson, who has a secondary appointment in the Swanson School’s Department of Bioengineering. “Now that we know about this first phase, we can begin to investigate how to promote it in patients with aneurysms, and how factors like age and preexisting conditions affect this ability and may place a patient at higher risk for aneurysm rupture.” The investigative team includes Robertson and graduate students Chao Sang and Michael Durka from Pitt, Simon Watkins from the Center for Biologic Imaging, and David Kallmes, Ramanathan Kadirvel, Yong Hong Ding, and Daying Dai from the Mayo Clinic’s Department of Radiology. The paper, “Adaptive Remodeling in the Elastase-Induced Rabbit Aneurysms,” (DOI:10.1007/s11340-020-00671-9) was published in the journal Experimental Mechanics and was authored by Chao Sang, Michael Durka and Anne Robertson at the Swanson School; David Kallmes, Ramanathan Kadirvel, Yong Hong Ding and Daying Dai at the Mayo Clinic’s Department of Radiology; Simon Watkins at Pitt’s Center for Biologic Imaging.
Maggie Pavlick

Jan

13

2021

Breathing Easier with a Better Tracheal Stent

Bioengineering, Chemical & Petroleum, MEMS

PITTSBURGH (Jan. 13, 2021) — Pediatric laryngotracheal stenosis (LTS), a narrowing of the airway in children, is a complex medical condition. While it can be something a child is born with or caused by injury, the condition can result in a life-threatening emergency if untreated. Treatment, however, is challenging. Depending on the severity, doctors will use a combination of endoscopic techniques, surgical repair, tracheostomy, or deployment of stents to hold the airway open and enable breathing. While stents are great at holding the airway open and simultaneously allowing the trachea to continue growing, they can move around, or cause damage when they’re eventually removed. New research published in Communications Biology and led by the University of Pittsburgh is poised to drastically improve the use of stents, demonstrating for the first time the successful use of a completely biodegradable magnesium-alloy tracheal stent that avoids some of these risks. “Using commercial non-biodegradable metal or silicone based tracheal stents has a risk of severe complications and doesn't achieve optimal clinical outcomes, even in adults,” said Prashant N. Kumta, Edward R. Weidlein Chair Professor of bioengineering at the Swanson School of Engineering. “Using advanced biomaterials could offer a less invasive, and more successful, treatment option.” In the study, the balloon-expandable ultra-high ductility (UHD) biodegradable magnesium stent was shown to perform better than current metallic non-biodegradable stents in use in both in lab testing and in rabbit models. The stent was shown to keep the airway open over time and have low degradation rates, displaying normal healing and no adverse problems. “Our results are very promising for the use of this novel biodegradable, high ductility metal stent, particularly for pediatric patients,” said Kumta, who also holds appointments in Chemical and Petroleum Engineering, Mechanical Engineering and Materials Science, and the McGowan Institute for Regenerative Medicine. “We hope this new approach leads to new and improved treatments for patients with this complex condition as well as other tracheal obstruction conditions including tracheal cancer.” The paper, “In-vivo efficacy of biodegradable ultrahigh ductility Mg-Li-Zn alloy tracheal stents for pediatric airway obstruction,” (DOI: 10.1038/s42003-020-01400-7), was authored by the Swanson School’s Jingyao Wu, Abhijit Roy, Bouen Lee, Youngjae Chun, William R. Wagner, and Prashant N. Kumta; UPMC’s Leila Mady, Ali Mübin Aral, Toma Catalin, Humberto E. Trejo Bittar, and David Chi; and Feng Zheng and Ke Yang from The Institute of Metal Research at the Chinese Academy of Sciences.
Maggie Pavlick

Jan

12

2021

“Bluetooth Bacteria” Wins a Gold Medal at iGEM 2020

Bioengineering, Chemical & Petroleum, Student Profiles

PITTSBURGH (January 12, 2021) … Wi-Fi and Bluetooth technology have provided an invaluable connection to the workplace and the outside world as we remained sheltered at home in 2020. As part of a virtual research competition, a team of University of Pittsburgh undergraduates explored if a comparable equivalent to this ubiquitous technology could allow scientists to wirelessly manipulate cell behavior and control gene expression. The group pitched this idea for the 2020 International Genetically Engineered Machine (iGEM) competition, an annual synthetic biology research competition in which teams from around the world design and carry out projects to solve an open research or societal problem. More than 250 teams participated in the organization’s first Virtual Giant Jamboree, and the Pitt undergraduate group received a gold medal for their project titled “Bluetooth Bacteria.” This year’s group was also one of three teams that were nominated for “Best Foundational Advance Project.” This is the first time a Pitt iGEM team has been nominated for an award at the iGEM competition. The team included one Swanson School of Engineering student: Lia Franco, a chemical engineering junior. Other members included Sabrina Catalano, a senior molecular biology student; Dara Czernikowski, a senior biological sciences student; Victor So, a senior microbiology and English literature student; and Chenming (Angel) Zheng, a junior molecular biology student. “This sort of non-invasive technology could be used for timed drug release, synthetic organ and neuron stimulation, or even industrial applications,” Czernikowski said. “We first considered optogenetics, which uses light to manipulate cell behavior, but this strategy cannot target deep tissue without risky invasive methods so we needed to change our approach.” The team ultimately decided to attach magnetic nanoparticles to the surface of bacteria and stimulate them with an alternating magnetic field (AMF). The nanoparticles react to the AMF stimulation and dissipate heat, causing the temperature of the bacterium’s cytoplasm to rise. They then used a protein dimer to act as a “bio-switch” to control gene expression. “At lower temperatures, the protein dimers bind to a target DNA sequence and turn off gene expression, but at higher temperatures, heat causes the proteins to un-dimerize,” Catalano explained. “In its un-dimerized state, it can no longer inhibit gene expression, turning the system on. The change in temperature is controlled by the stimulation of magnetic nanoparticles with AMF, allowing wireless control of gene expression in bacteria.” The team hopes that there is therapeutic potential for their design but recognizes that they need to improve spatial control in order to match techniques like optogenetics. They would like to improve their design to use localized heating that could selectively target one bacterium or a specific region of the cytoplasm. They plan to continue development during the upcoming semester. “The iGEM competition is a unique experience where undergraduates take charge and develop and execute their own research idea, with close mentorship from a set of faculty mentors,” said W. Seth Childers, assistant professor of chemistry at Pitt and one of five faculty advisors for the Bluetooth Bacteria team. “This year’s team worked hard under the stress of a pandemic to bring together engineering and biology concepts to consider how one could wirelessly control a bacterium.” Another unique aspect of their project is the “Bluetooth Bacteria Podcast” – a casual and conversational podcast that seeks to educate the general population on topics and current developments in synthetic biology. “One of our main project goals was effective science communication,” said Catalano. “Because COVID-19 limited our ability to teach synthetic biology in person, we thought it would be fun to make a podcast as it is accessible to a wide audience. It gave us the opportunity to hear from iGEM teams all over the world, including France, London, and India.” The team published two episodes every week, and they are available on Apple Podcast or Spotify. The other faculty advisors include Alex Deiters, professor of chemistry; Jason Lohmueller, assistant professor of surgery and immunology; Jason Shoemaker, assistant professor of chemical and petroleum engineering; and Sanjeev Shroff, Distinguished Professor and Gerald E. McGinnis Chair of Bioengineering. # # # The team was sponsored by the University of Pittsburgh, Pitt’s Swanson School of Engineering, Pitt’s Department of Bioengineering, the Richard King Mellon Foundation, Open Philanthropy, Integrated DNA Technologies, TWIST Bioscience, GenScript, Ginkgo Bioworks, Benchling, Revive & Restore, SnapGene, MathWorks, New England BioLabs Inc., and Promega. Photo caption: (from left) Sabrina Catalano, Dara Czernikowski, Lia Franco, Victor So, and Chenming (Angel) Zheng.