Dr. Stephen Badylak Named Inaugural Winner of the Jensen Tissue Engineering Award
McGowan Institute for Regenerative Medicine Deputy Director Stephen Badylak, DVM, PhD, MD, is the inaugural winner of the Jensen Tissue Engineering Award. This award—a gift from Ole Jensen, DDS, MS, a world-renowned oral surgeon and innovative businessman—was established “to recognize an individual (anywhere in the world) for sustained scientific contributions, translational impact towards clinical realization, and professional distinction in the field of tissue engineering and regenerative medicine.” Dr. Badylak will receive his award during the upcoming TERMIS-AM Meeting in Toronto between July 10-13, 2022.
Dr. Badylak’s greatest contributions to the science of bioengineering and medicine, as well as the practice of medicine, are his pioneering efforts in the late 1980’s and early 1990’s in the development, commercialization, and clinical application of biologically derived materials to form surgical meshes, powders, and hydrogels that promote constructive and functional tissue repair. His core technology has resulted in more than 70 issued US patents and is the basis of more than 100 FDA-approved medical devices that are used in every major body system. More than 13 million patients have been treated with, and benefited from, his work to date.
Dr. Badylak has been referred to as the “father of biologic scaffolds—particularly those composed of extracellular matrix (ECM). Since his early discoveries in the late 1980’s to the present day, he has challenged existing concepts of tissue repair and identified key physical and molecular signals that influence the host-wound healing response. He was the first in the field of regenerative medicine to emphasize the importance and relevance of the immune system in both tissue/organ development and in the successful and functional outcomes that result from biomaterial approaches to tissue repair. He is internationally recognized for his contributions and has successfully translated the use of such materials for treating unmet medical problems such as volumetric muscle loss and esophageal cancer. He has also edited two textbooks based upon the mammalian response to such translational biomaterials: “The Host Response to Biomaterials” and “Immunomodulatory Biomaterials”.
In addition to holding over 70 issued US patents, Dr. Badylak holds 400 patents worldwide and has authored more than 400 scientific publications and 60 book chapters. Dr. Badylak has a Scopus H-index of 114, a testament to the impact of his work upon both the medical field and basic science. He is passionately committed to seeing his emerging technologies become clinically available. He has served as the Chair of the Study Section for the Small Business Innovative Research (SBIR) at the National Institutes of Health (NIH), and as chair of the Bioengineering, Technology, and Surgical Sciences (BTSS) Study Section at NIH and is now a member of the College of Scientific Reviewers. Dr. Badylak has either chaired or been a member of the Scientific Advisory Board to several major medical device companies and has been the founder of two medical device companies: ACell, Inc., (now part of Integra) and ECM Therapeutics, Inc., the latter which is actively developing products in several different clinical markets including gastrointestinal, musculoskeletal, cardiovascular, and the central nervous system.
Dr. Badylak is currently a Professor in the Department of Surgery, University of Pittsburgh, with a secondary Professorship in the Department of Bioengineering. Dr. Badylak also serves as the Director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute.
Congratulations, Dr. Badylak!
RESOURCES AT THE MCGOWAN INSTITUTE
July Histology Special – TUNEL Assay
Apoptosis, or “programmed cell death”, is a form of cell death designed to eliminate compromised or senescent cells. Apoptosis is controlled by multiple signaling and effector pathways that in turn, are activated in response to external growth, survival, or death factors.
A method for examining apoptosis via DNA fragmentation is the TUNEL assay. This technique can detect early-stage apoptosis in systems where chromatin condensation has begun and strand breaks are fewer, even before the nucleus undergoes recognizable morphologic changes.
You’ll receive 30% off TUNEL staining in July when you mention this ad.
Contact Julia at the McGowan Core Histology Lab by email: Hartj5@upmc.edu or call 412-624-5265.
Sample Submission Procedures: In response to COVID-19, we ask that you contact us to schedule a drop off time. When you arrive at the building you can call our laboratory at (412) 624-5365. Someone will meet you in the lobby to collect your samples. When your samples are completed, you will receive an email to schedule a pickup time.
McGowan Institute for Regenerative Medicine Spotlight: Antonio D’Amore, PhD
Since 2011, Antonio D’Amore, PhD, has been with the McGowan Institute for Regenerative Medicine initially serving as a post-doc in tissue engineering and biomechanics in the laboratory of McGowan Institute Director William Wagner, PhD. He continued from 2013-2016 as a Research Associate, and in early 2017 he moved into his current position of Research Assistant Professor.
Since 2008, Dr. D’Amore has been a bioengineering industry consultant in both the U.S. and Italy. He is a group leader and head of the cardiac tissue engineering program at Fondazione RiMED. RiMED is an international partnership between the Italian Government, the University of Pittsburgh, and the University of Pittsburgh Medical Center aiming to establish a world-class biomedical research and biotechnology center in Europe. His middle term mission as a RiMED investigator was to establish a successful cardiovascular tissue engineering program in Italy at the Biomedical Research and Biotechnology Center. The RiMED Cardiac Tissue Engineering laboratory was established in 2020 and is located in Palermo, Italy.
Earlier in 2022, Dr. D’Amore was elected to the rank of the National Academy of Inventors (NAI) Senior Member. He was honored for his achievements and contributions to the innovation ecosystem at the NAI Member Institution, University of Pittsburgh, and for his “success in patents, licensing, and commercialization” and for producing “technologies that have brought, or aspire to bring, real impact on the welfare of society.” Dr. D’Amore was inducted as an elected Class of 2022 NAI Senior Member at the NAI 11th Annual Meeting on June 14-15, 2022, in Phoenix, Arizona.
Dr. D’Amore was elated with this honor and was thankful to “his mentor Dr. Wagner and faculty members at McGowan, BioE and Surgery that over the years have instilled the passion for translating technology. I also would like to thank the RiMED Foundation for supporting my work for many years at Pitt and even more strongly now while building the infrastructure for a new laboratory. ISMETT is our important clinical research partner in Palermo. I would like to thank Dr. Luca for facilitating interactions with UPMC Italy clinicians and Dr. Pilato for his friendship and support on the “BIOMITRAL” European Research Council (ERC)-funded project that really could not happen without the help of the stellar surgeons in his groups.”
From 2007, he has been the recipient of two pre-doctoral, two post-doctoral, and a number of other research awards he obtained as PI or Co-I, which cumulatively secured funding for more than $9.7M. Dr. D’Amore is the co-founder and Chief Technology Officer of Neoolife, a University of Pittsburgh – RiMED startup focusing on tissue engineering heart valve technology.
Dr. D’Amore has recently been named PI on two research projects to be carried out in collaboration with the University of Pittsburgh. In 2021, he received an ERC Consolidator Grant Award entitled “BIOMITRAL.” The focus of this project is on bio-inspired mitral valve enhanced functional and remodeling performances. The host institution is Fondazione RiMED for $2M for 5 years. The ERC, set up by the European Union in 2007, is the premier European funding organization for excellent frontier research.
Also in 2021, Dr. D’Amore received a 9-month, $412K ADEKA-sponsored award focused on the structural characterization and host response to implantation of biomaterials for cardiac repair. ADEKA is a Japanese chemical company with more than a century of experience in the development and production of a wide range of unique products with high technical strength and reliable quality.
Another lifetime realization Dr. D’Amore is most proud of is on April 14, 2022, he became a U.S. citizen. He says, “There was a personal journey that led me to become a U.S. citizen. I think this is even a more important accomplishment. Because it was a personal choice in the matter, I chose to be American because my experience here as a human being has been extremely compelling. What I loved about this part of the journey was to experience a new way of living where identity is really at the center of society, and that is the best for scientists who feed and grow and create their own scientific identity. It’s a very nice coincidence that the number of my professional accolades I’m experiencing meet on my personal timeline exactly when my citizenship came.”
Dr. D’Amore recently spoke with Regenerative Medicine Today host John Murphy, McGowan Institute Executive Director, about many of these personal achievements and the scientific background information on his current research efforts. Listen to their latest conversation here. Dr. D’Amore’s 2017 visit on Regenerative Medicine Today is here.
Sensing Signals in Paralyzed Muscles
For people with tetraplegia—a condition in which all four limbs have lost motor ability—regaining independence is a top priority. Although there is no cure for paralysis caused by neurological disorders, robotic arms and exoskeletons may provide some assistance. Controlling these robotic devices, however, is a complex problem. Researchers have experimented with voice control (which struggles to translate verbal commands into a three-dimensional space), brain-computer interfaces (which require complex surgery), and joysticks (which often mean multiple rounds of positioning for each arm segment).
McGowan Institute for Regenerative Medicine affiliated faculty member Douglas Weber, PhD, a Carnegie Mellon University professor of mechanical engineering and the Neuroscience Institute, and a collaborator in the Rehab Neural Engineering Labs at the University of Pittsburgh, partnered with an international team of researchers to explore the possibility of using myoelectric signals—the electrical pulses associated with muscle contraction—to predict intended hand gestures in a person with tetraplegia. Researchers from Imperial College in London, the Battelle Memorial Institute in Ohio, and the University of Pittsburgh were also involved in the project.
“A lot of the work that we do in the lab is focused on assisting people with the recovery of motor functions that are important for accomplishing daily activities,” Dr. Weber said. “We work at the intersection of engineering and neuroscience, trying to create devices that connect with functioning parts of the body and bypassing areas of the nervous system that are damaged by injury or disease.”
There are a variety of conditions and injuries that can lead to paralysis or loss of movement. Some, like stroke, affect the brain. Others, like spinal cord injuries, affect the connections between the brain and muscles. The traditional understanding has been that spinal cord injuries sever the connection, and signals don’t ever reach the muscles. The idea follows that people with tetraplegia would be unable to generate detectable myoelectric signals.
“We set out to challenge the notion that muscles paralyzed by spinal cord injury are incapable of expressing myoelectric activity, which indicates someone’s motor intention,” said Dr. Weber. “We used a sleeve embedded with 150 sensors that covered the entire forearm—casting a wide net in the hope of finding myoelectric signals that persist even in muscles that are too weak to generate physical action.”
This approach was tested in a 32-year-old man who suffered a spinal cord injury 14 years prior to the study. He has some limited movement in his wrist, but his fingers cannot move. During testing, the participant was instructed to try mimicking a set of hand gestures, such as pointing with the index finger, that were displayed as prompts on a computer screen.
“We knew we were asking the participant to perform an impossible task, and thus we were pleasantly surprised to find that each (failed) attempt to move produced small but noticeable bursts in muscle activity,” said Jordyn Ting, a PhD candidate in bioengineering and the Rehab Neural Engineering Labs at the University of Pittsburgh and lead author on this paper.
This means that the participant’s muscles were still connected to the brain, though those connections are weak. The strength and location of myoelectric signals depends on the individual patient and their unique injury—no two are exactly the same. Similarly, the signals can differ from what one would detect in a healthy person. Despite the challenges associated with interpreting the signals, their presence suggests that they could be used to control robotic devices for assisting movement. Next, the researchers will use virtual reality to show patients that, despite the lack of movement, their muscles are communicating with the brain.
“That feedback, we believe, may help them get stronger, just like when we practice any other skill,” Dr. Weber said. “We know we won’t be able to cure paralysis, but if we can enable someone to express their intentions through this wearable sensor, then we’ve empowered them to operate assistive devices in a very natural way using just their muscles.”
Ketogenic Diet Helps Mouse Muscle Stem Cells Survive Stress
Fasting sends muscle stem cells into a deep resting state that slows muscle repair but also makes them more resistant to stress, according to a Stanford Medicine study of laboratory mice. Thomas Rando, MD, PhD (pictured), director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and an affiliated faculty member of the McGowan Institute for Regenerative Medicine, is the study’s lead author.
The protective effect can also be achieved by feeding the mice high-fat, low-carbohydrate food — also known as a ketogenic diet — that mimics how the body responds to fasting, or by giving the animals ketone bodies, the byproducts that occur when the body uses fat as an energy source.
The research explores how the body responds in times of deprivation and plenty and gives clues about the effect of aging on the ability to regenerate and repair damaged tissue. Although the study focused on muscle stem cells, the researchers believe the findings are applicable to other types of tissue throughout the body.
“As we age, we experience slower and less complete healing of our tissues,” said Dr. Rando, professor of neurology and neurological sciences, recently accepted the director position at the Broad Stem Cell Research Center. “We wanted to understand what controls that regenerative ability and how fasting impacts this process. We found that fasting induces resilience in muscle stem cells so that they survive during deprivation and are available to repair muscle when nutrients are again available.”
The study was published online in Cell Metabolism and instructor Daniel Benjamin, PhD, and graduate student Pieter Both are the lead authors.
It’s been well documented that long-term caloric restriction extends the lifespan and promotes the overall health of laboratory animals, but it is difficult for people to maintain a very-low-calorie diet for months or years. Periodic fasting has been explored as another way to obtain the health benefits of caloric restriction, but the effects of intermittent fasting on the body and its ability to regenerate damaged or aging tissues have not been well studied.
Fasting or, alternatively, eating a ketogenic diet high in fat and low in carbohydrates — a popular weight-loss technique — causes the body to enter a state called ketosis, in which fat is the primary energy source. Ketone bodies are the byproducts of fat metabolism.
The researchers found that mice that had fasted between 1 and 2.5 days were less able than non-fasting animals to regenerate new muscle in their hind legs in response to injury. This reduced regenerative capacity persisted for up to three days after the mice began feeding again and returned to a normal body weight; it returned to normal within one week of the end of the fast.
Further research showed that muscle stem cells from fasting animals were smaller and divided more slowly than those from non-fasting animals. But they were also more resilient: They survived better when grown on a lab dish under challenging conditions including nutrient deprivation, exposure to cell-damaging chemicals, and radiation. They also survived transplantation back into animals better than those from non-fasting animals.
“Usually, most laboratory-grown muscle stem cells die when transplanted,” Dr. Rando said. “But these cells are in a deep resting state we call ketone-induced deep quiescence that allows them to withstand many kinds of stress.”
Muscle stem cells isolated from non-fasting animals and then treated with a ketone body called beta-hydroxybutyrate (BHB) displayed a similar resilience as did those from fasting animals, the researchers found. Additionally, muscle stem cells isolated from mice fed a ketogenic diet, or a normal diet coupled with injections of ketone bodies, displayed the same characteristics of the deeply quiescent stem cells from fasting animals.
Finally, the researchers isolated muscle stem cells from old mice that had been treated with ketone bodies for one week. Previous research in Dr. Rando’s lab showed that these aged muscle stem cells grew more poorly in the laboratory than muscle stem cells from younger animals. But treatment with the ketone bodies allowed the old muscle stem cells to survive as well as their younger counterparts.
Although more research needs to be done, the results are intriguing, the researchers said.
“Cells evolved to exist in times of abundance and in times of deprivation,” Dr. Rando said. “They had to be able to survive when food was not readily available. Ketone bodies arise when the body uses fat for energy, but they also push stem cells into a quiescent state that protects them during deprivation. In this state, they are protected from environmental stress, but they are also less able to regenerate damaged tissue.”
Balancing these outcomes might one day help combat normal aging and enhance stem cell function throughout the body, the researchers speculated.
“It would be beneficial if the effects of fasting on stem cells could be attained through ketone bodies, supplanting the need to fast or to eat a ketogenic diet,” Dr. Rando said. “Perhaps it may be possible to eat normally and still get this increased resilience.”
Dancing in the Light
University of Pittsburgh Distinguished Professor and McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD (pictured), collaborated with Harvard University senior author Joanna Aizenberg, PhD, the Amy Smith Berylson Professor of Materials Science and Professor of Chemistry and Chemical Biology at the John A. Paulson School of Engineering and Applied Sciences (SEAS), on research published in Nature. Mastering control over the dynamic interplay among optical, chemical, and mechanical behavior in single-material, liquid crystalline elastomers, results in microposts that combine bending, twisting, and turning into complex dances. The advancement could contribute toward further development of soft robotics and other devices.
When humans twist and turn it is the result of complex internal functions: the body’s nervous system signals our intentions; the musculoskeletal system supports the motion; and the digestive system generates the energy to power the move. The body seamlessly integrates these activities without our even being aware that coordinated, dynamic processes are taking place. Reproducing similar, integrated functioning in a single synthetic material has proven difficult—few one-component materials naturally encompass the spatial and temporal coordination needed to mimic the spontaneity and dexterity of biological behavior.
Inspired by experiments performed in the Aizenberg Lab, Dr. Balazs and James Waters, PhD, developed the theoretical and computational models to design liquid crystal elastomers (LCEs) that imitate the seamless coupling of dynamic processes observed in living systems.
“Our movements occur spontaneously because the human body contains several interconnected structures, and the performance of each structure is highly coordinated in space and time, allowing one event to instigate the behavior in another part of the body,” explained Dr. Balazs, Distinguished Professor of Chemical Engineering and the John A. Swanson Chair of Engineering. “For example, the firing of neurons in the spine triggers a signal that causes a particular muscle to contract; the muscle expands when the neurons have stopped firing, allowing the body to return to its relaxed shape. If we could replicate this level of interlocking, multi-functionality in a synthetic material, we could ultimately devise effective self-regulating, autonomously operating devices.”
The LCE material used in this collaborative Harvard-Pitt study was composed of long polymer chains with rod-like groups (mesogens) attached via side branches; photo-responsive crosslinkers were used to make the LCE responsive to UV light. The material was molded into micron-scale posts anchored to an underlying surface. The Harvard team then demonstrated an extremely diverse set of complex motions that the microstructures can display when exposed to light. “The coupling among microscopic units—the polymers, side chains, meogens and crosslinkers—within this material could remind you of the interlocking of different components within a human body” said Dr. Balazs, “suggesting that with the right trigger, the LCE might display rich spatiotemporal behavior.”
To devise the most effective triggers, Dr. Waters formulated a model that describes the simultaneous optical, chemical, and mechanical phenomena occurring over the range of length and time scales that characterize the LCE. The simulations also provided an effective means of uncovering and visualizing the complex interactions within this responsive opto-chemo-mechanical system.
“Our model can accurately predict the spatial and temporal evolution of the posts and reveal how different behaviors can be triggered by varying the materials’ properties and features of the imposed light,” Dr. Waters said, further noting, “The model serves as a particularly useful predictive tool when the complexity of the system is increased by, for example, introducing multiple interacting posts, which can be arranged in an essentially infinite number of ways.”
According to Dr. Balazs, these combined modeling and experimental studies pave the way for creating the next generation of light-responsive, soft machines or robots that begin to exhibit life-like autonomy. “Light is a particularly useful stimulus for activating these materials since the light source can be easily moved to instigate motion in different parts of the post or collection of posts,” she said.
In future studies, Drs. Waters and Balazs will investigate how arrays of posts and posts with different geometries behave under the influence of multiple or more localized beams of light. Preliminary results indicate that in the presence of multiple light beams, the LCE posts can mimic the movement and flexibility of fingers, suggesting new routes for designing soft robotic hands that can be manipulated with light.
“The vast design space for individual and collective motions is potentially transformative for soft robotics, micro-walkers, sensors, and robust information encryption systems,” said Dr. Aizenberg.
LivaNova PLC Acquires ALung Technologies, Inc.
ALung Technologies, Inc., the leading provider of low-flow extracorporeal carbon dioxide removal (ECCO2R) technologies for treating patients with acute respiratory failure, has been acquired by LivaNova PLC, a London-based medical products manufacturer.
The ALung sale comes just six months after the company received FDA approval to market its artificial lung system, the Hemolung Respiratory Assist System. FDA approval opened the door to marketing the product for treatment of severe asthma, cystic fibrosis, and as a bridge to organ transplant. The company began merger discussions with LivaNova in 2018, ALung’s former Chairman and CEO Peter DeComo said. ALung was founded in 1997 as a spin-out company of the University of Pittsburgh.
This system was developed at the McGowan Institute for Regenerative Medicine by a team of researchers led by faculty member William Federspiel, PhD (pictured), the company’s cofounder and professor of bioengineering, chemical engineering, critical care medicine, and the Clinical Translation Institute at the University of Pittsburgh. Dr. Federspiel is also the director of the Medical Devices Laboratory at the McGowan Institute.
The Hemolung is a first-of-its-kind, comprehensive, all-in-one system intended to provide minimally invasive, low-flow ECCO2R. Low-flow ECCO2R with the Hemolung is a lung-independent ventilatory support therapy for removal of CO2 waste molecules from venous blood via extracorporeal circulation through a single, 15.5 French, central venous catheter at blood flows of 350 – 550 mL/min. Respiratory failure patients often experience the need for CO2 removal without the need for supplemental oxygen. Historically, when extracorporeal therapy was indicated for the removal of CO2, extracorporeal membrane oxygenation (ECMO) devices were utilized because other alternatives were not available. ECMO is typically necessary when respiratory failure patients have a significant oxygenation issue. ECMO systems are complex, invasive, require high blood flows and as a result, require specialty personnel to monitor both the technology and the patient. The Hemolung offers ICU physicians, nurses, respiratory therapists and perfusionists a new tool to treat respiratory failure patients in a less complex, costly, and invasive manner.
Pitt Spinout Company, Oncorus, Moves Forward
Oncorus, Inc., is a viral immunotherapies company founded in 2016 which is focused on driving innovation to transform outcomes for cancer patients, and is a company spun out of the University of Pittsburgh. The technology for the Massachusetts-based company was licensed from Pitt from the lab of Joseph Glorioso, PhD, professor of microbiology and molecular genetics in Pitt’s School of Medicine and an affiliated faculty member of the McGowan Institute for Regenerative Medicine. Dr. Glorioso was one of the founders of Oncorus and is chair of the company’s scientific advisory board.
Oncorus announced that it has entered into a loan and security agreement with K2 HealthVentures (K2HV), a healthcare focused specialty finance company. Also, Oncorus announced plans to relocate all its operations to its facility in Andover, Massachusetts, in the fourth quarter of 2022, to allow research, process development, and Good Manufacturing Practice (GMP)-compliant manufacturing to occur all in one facility. As a result of the term loan facility and operations relocation, as well as other initiatives to increase operational efficiency, Oncorus now expects its cash, cash equivalents, and investments to fund its capital expenditures and operating expenses into early 2024.
The University of Pittsburgh Will Compete for $10 Billion in Military Health Contracts
The University of Pittsburgh has joined a select pool of 56 organizations — and just two universities — to compete for as much as $10 billion in contracts from the Department of Defense to develop health care innovations benefiting both wounded warriors and civilians over the next five years.
“Southwestern PA has one of the highest populations of military veterans in the country, and we at Pitt are all in on supporting both the Department of Defense and our VA community,” said McGowan Institute for Regenerative Medicine affiliated faculty member Ron Poropatich, MD (pictured top), a School of Medicine professor and one of the project’s two leaders. “We’re trying to build out a defense innovation economy for Pittsburgh.”
Over the next five years, the Defense Health Agency as part of its Omnibus IV solicitation will issue requests for proposals to complete contracts related to military health, spanning research areas such as trauma care, veteran quality of life, and acute field care. Pitt, leading a consortium of eight academic and 64 industry partners, will pursue those contracts. The McGowan Institute and the Center for Military Medicine Research will be at the helm.
“This confirms that the Department of Defense recognizes Pitt as a nationally known, reliable and valued team player in medical research,” said Senior Vice Chancellor for Research Rob Rutenbar, PhD. “Pitt is now positioned to deliver real health solutions by leading on R&D projects and partnering on translational science that will help improve the lives of service members and military health system patients over the coming decade.”
“We are delighted to build on the long-standing medical research commitment to the Department of Defense’s Defense Health Agency with our deep and talented Schools of Health Sciences at Pitt in collaboration with many other outstanding university and industry partners,” said Senior Vice Chancellor for the Health Sciences and the John and Gertrude Petersen Dean of Pitt’s School of Medicine Anantha Shekhar, PhD.
Pitt’s legacy of defense-related research
The accomplishment is a testament to Pitt’s recent and growing success in conducting Department of Defense-sponsored research, Dr. Poropatich said. He and other University researchers have engaged in a years-long effort of aligning Pitt research with the needs of the armed services, including by working closely with physicians at military hospitals to understand their needs as well as what they predict their needs may be in future conflicts.
Those efforts have borne fruit: The Center for Military Medicine Research, which Dr. Poropatich leads, has grown to assisting with about $55 million a year in Department of Defense funding, driving Pitt research that advances health care for service members and veterans.
“We span the entire spectrum, from medical research to getting technology to companies and patients, like few universities are able to,” said project leader William Wagner, PhD (pictured bottom), a distinguished professor of surgery, chemical engineering and bioengineering and director of the McGowan Institute.
One example is the work of Department of Orthopaedic Surgery Associate Professor Anthony Kontos, PhD, whose research on diagnosing concussions by measuring rapid eye movements has made its way to the battlefield as part of a formal system for evaluating concussion symptoms.
Advances like these also lead to improvement in health care off the battlefield, especially in rural areas where patients may not be able to quickly get access to a hospital. “Research on traumatic brain injuries, post-traumatic stress — everything in our portfolio has direct relevance to civilian needs,” said Dr. Poropatich.
Dr. Wagner also cited Pitt’s Center for Vaccine Research and Human Engineering Research Laboratories as leaders in two areas of keen interest to the Department of Defense.
How small businesses will play a role
Of the agency’s four market segments, Pitt will lead efforts to pursue contracts in two — research and development along with translational science support and services — and has partnered with other organizations to pursue contracts in the other two areas. After the five-year term of the request, the Defense Health Agency may extend it for an additional five years with more funding.
The agency requires that one quarter of each project be completed by an industry partner — so Pitt’s consortium includes more than 50 small businesses as well as other industry partners, the result of an effort by Director of Partnerships Brian Vidic, MS, and others in the Office of Industry and Economic Partnerships to build lasting relationships with industry. The group involves a broad mix of companies across the United States with expertise in research and translation, and that number will only increase over the next five years as Pitt adds more partners.
“Innovation is a team sport,” said Office of Industry and Economic Partnerships Director Scott Morley, MBA. “Collaboration with industry is crucial to ensuring that new health care solutions can be delivered to patients, including our men and women in uniform. Our partners in this effort bring skills in clinical and commercial translation that are complementary to Pitt’s research and development expertise.”
Along with a number of women-owned businesses and disabled veteran-owned businesses, the consortium includes more than a half dozen startups that have been spun out of the University.
“Pitt is very committed to this whole ecosystem that has been designed to drive true impact from research,” said Mr. Morley. “And we’ve set ourselves up for success on that front.”
More than just medicine
At Pitt, the effort has stretched across the entire University, including the Office of Sponsored Programs, the School of Pharmacy’s Program Evaluation Research Unit, and academic units across the Schools of Health Sciences and Swanson School of Engineering. Pitt will also collaborate with other universities to pursue contracts, including Carnegie Mellon University, Howard University, and North Carolina A&T State University, among others.
The result is a team ready to jump on potentially billions of dollars of contracts at a moment’s notice.
“I don’t know that 20 years ago we would have had the track record to do this. It reflects broad effort across the University and the health system in the area of military medicine,” said Dr. Wagner. “We have the history, the skills, and the partners, and we can show our technologies getting to patients. I think our team is going to be very competitive.”
Small Package, Big Potential to Help Cell-Based Therapies
Cell-based therapies have long been thought of as an alternative treatment option for patients with a range of diseases caused by organ and tissue failure, inclusive of heart attack, diabetes, corneal blindness, and cystic fibrosis. While great in theory, in practice these therapies show limited clinical success in many applications due to low cell viability after injection, as well as poor retention at the injection site and engraftment into damaged tissue. Ongoing research led by Carnegie Mellon University (CMU) Biomedical Engineering’s Rachelle Palchesko, PhD, and Adam Feinberg, PhD, is exploring the use of a new cell delivery method to help cells stick and stay where they’re needed most. Dr. Feinberg is an affiliated faculty member of the McGowan Institute for Regenerative Medicine as well is Yiqin Du, MD, PhD, a University of Pittsburgh co-author of the paper.
More than 50,000 cornea transplant procedures are performed in the United States annually, an impressive statistic that exceeds the number of transplants of all other solid organs combined. In new research published in Communications Materials, CMU and University of Pittsburgh researchers propose using a small package of shrink-wrapped corneal endothelial cells as a potential alternative to cornea transplant when low endothelial cell density is the cause of corneal blindness.
The corneal endothelium (CE) is a single layer of cells that lines the back surface of the cornea and is responsible for maintaining proper corneal thickness and clarity. Nearly half of all cornea transplants stem from failure of the CE, primarily due to a loss of cells that cannot replicate to repair damage or injury.
While some treatments for CE failure exist, chronic rejection and limited donor supply have motivated the development of new methods to inject CE cells to repopulate the corneal endothelium and restore function. Until now, most approaches have required the existing CE to be removed through scraping or cryogenic injury of the cornea to provide a place for the delivered cells to attach.
“You can imagine if you’re trying to take a healthy cell and put it in a hostile tissue, it doesn’t want to stay there,” explained Dr. Palchesko, special faculty researcher of biomedical engineering. “We had a benchmark for effective application of shrink-wrapped cells in the cornea based on some work a group in Japan was doing, and we knew we could improve upon it. We’ve been able to show that we can package cells effectively and get them to integrate into high-density tissues, without inducing any injury or removing any cells. Our technology can improve cell therapies and help cells stick and stay where we want them to.”
The group’s technique utilizes shrink-wrapping micropatterned islands of corneal endothelial cells in a basement membrane-like layer of extracellular matrix that enables the cells to maintain their cell-cell junctions and cytoskeletal structure while in suspension. In a series of studies, the small packages of cells exhibited an ability to rapidly engraft into intact, high-density corneal endothelial monolayers in both in vitro and in vivo model systems.
“The bulk of my research has been in treating corneal blindness however we believe this technology has strong potential to be applied to other areas of the body,” said Dr. Palchesko. “Our group in the lab is investigating how to apply this technology to treat cystic fibrosis or deliver cells after a heart attack.”
“Imagine that organ failure could be prevented with a simple injection into the affected tissue instead of waiting for a transplant that may never come,” said Dr. Feinberg, a professor of biomedical engineering and materials science and engineering. “This is the truly exciting potential of the technology as it is further developed and validated. And we are thankful for the support of the National Institutes of Health and Cystic Fibrosis Foundation in funding this research.”
Dr. Palchesko added, “This is a simple, effective technology — it’s not overly engineered; we’re just wrapping up these cells in little packages. I believe we can take it farther and help a lot of people.”
Dr. Du is an Associate Professor in the Departments of Ophthalmology, Cell Biology and Developmental Biology at the University of Pittsburgh School of Medicine and the Louis J. Fox Center for Vision Restoration.
Illustration: Feinberg Laboratory.
Endovascular Orifice Detection Device for In Situ Fenestration of AAA
The primary conduit for blood, known as the aorta, can weaken and rupture in a significant percentage of the population. Reinforcement of the weakened aorta can be achieved by placement of a lining device known as a stent, but that can also block conduits that branch from the aorta causing further problems. A team of researchers co-led by Mohammad Eslami, MD, Professor of Surgery and Bioengineering, University of Pittsburgh, Director of Clinical Research, UPMC Division of Vascular Surgery, and Chief of Vascular Surgery, UPMC Mercy, and McGowan Institute for Regenerative Medicine affiliated faculty member David Vorp, PhD, Associate Dean for Research, Swanson School of Engineering, University of Pittsburgh, John A. Swanson Professor of Bioengineering, Co-Director of the Center for Medical Innovation, and the Director of the Vascular Bioengineering Laboratory, are developing a new method to create holes in the stent, while within the patient, to allow passage of blood to branching conduits.
This 2-year project entitled “Endovascular Orifice Detection (EOrD) Device for In Situ Fenestration of Abdominal Aortic Aneurysm” has been funded by the National Heart, Lung, and Blood Institute. The abstract reads:
Abdominal aortic aneurysm (AAA) is a localized dilatation of the aorta and if left untreated may go on to rupture which is associated with a 90% mortality rate. This is the 15th leading cause of death in the United States with more than 15,000 deaths reported annually. When an aneurysm reaches the maximum diameter criteria (greater than 5.0 – 5.5 cm), clinicians will intervene with either open surgery or endovascular repair (EVAR). For complex AAA cases, a minimally invasive fenestrated EVAR (FEVAR) is preferred over high-risk open surgery, however, fenestrated stent-grafts extend past the visceral arteries (renal, superior mesenteric artery and celiac artery) and must be revascularized after deployment requiring the stent-graft to be prefabricated. Currently, there is only one FDA-approved fenestrated graft on the market, the Cook Zenith Graft, that requires additional imaging for fabrication with a 6 – 8 week delivery time, costs up to 3 times more than traditional EVAR stent-grafts, and can be technically challenging when passing guidewires through the orifices of the fenestrations. The objective of this project is to develop a medical device for endovascular orifice detection (EOrD) which will both locate visceral arteries and perform in situ fenestration. This device can then be applied in the cases of AAA, ascending aneurysms, and traumatic aortic injury. Preliminary in vitro experiments were performed to determine whether visceral arteries could be detected through chelated sheep blood and stent-graft material using infrared (IR) waves. A scaled-up sensor array was built using phototransistors along with an analog to digital converter to detect the reflected IR waves. Distinct signal responses were collected while sweeping the sensor array over the orifice of the visceral artery, confirming feasibility. After an orifice of the visceral artery is detected, we plan to create a fenestration using a low-powered laser or mechanical puncturing mechanism that simultaneously inserts a guidewire to deploy the bridging stents. Our initial EOrD prototype with the proposed approach will be delivered through a catheter sheath and tested for orifice detection, puncture, and guidewire insertion using realistic in vitro AAA phantoms and cadavers. Continuous feedback from our clinical experts will improve design iterations to develop a final prototype that is able to reliably and reproducibly perform in situ fenestration of stent-grafts to treat aortic aneurysms. With our novel device, we can improve patient healthcare and reduce overall costs associated with AAA repair.
Illustration: University of Pittsburgh Department of Surgery (Eslami)/McGowan Institute for Regenerative Medicine (Vorp)
Dr. John Kellum and Colleagues Push for Prognostic Test to End ‘Silent Epidemic’
When someone comes to the hospital with signs of a heart attack, doctors use a battery of tests to help figure out what is happening, including an echocardiogram to image the heart and look at how it is functioning, as well as an electrocardiogram and plasma biomarkers to look for evidence of heart damage. Combined, these tests permit cardiologists to identify a heart attack quickly and accurately, a necessary first step to determine the best course to protect the remaining function of this vital organ.
This coupling of diagnostic and prognostic tests doesn’t exist for patients with acute kidney problems, and clinicians like McGowan Institute for Regenerative Medicine affiliated faculty member John Kellum, MD (pictured top)—Distinguished Professor and the UPMC Endowed Chair in Critical Care Research in the Department of Critical Care Medicine with secondary appointments in Medicine, Bioengineering, and Clinical and Translational Science at the University of Pittsburgh, and the Director of the Center for Critical Care Nephrology in the Department of Critical Care Medicine at UPMC—want that to change. He can diagnose a patient with acute kidney injury, but it isn’t so easy determining the extent of the damage and prescribing the best treatment to keep the kidneys—the twin organs responsible for filtering toxins and waste from the blood—functional.
“We call acute kidney injury the ‘silent epidemic,’” Dr. Kellum said. “The kidney doesn’t hurt when it’s injured, so until function is really bad, you don’t have symptoms. Often, patients present late with fully established renal failure, and it’s up to us doctors to put the pieces together to understand why.”
There are numerous causes of acute kidney injury—ranging from major surgery and tissue damage to ingesting a toxin or an infection—and patients with sepsis often have the condition. Hospitalizations for acute kidney injury in the U.S. have been on the rise, affecting nearly 12% of hospitalized patients and more than half of critically ill patients.
In an article published in JAMA Network Open, Dr. Kellum and his colleagues examine the possibility of measuring biomarkers—molecules found in the urine—to grade kidney damage in order to preserve remaining function without unnecessarily restricting the medications and foods a patient can have. McGowan Institute affiliated faculty member Derek Angus, MD (pictured bottom)—Distinguished Professor and the Mitchell P. Fink Endowed Chair in Critical Care Medicine at the University of Pittsburgh with secondary appointments in Medicine, Health Policy and Management, and Clinical and Translational Science, and Chair of the Department of Critical Care Medicine—is a co-author of the study.
“You cannot look at a patient with acute kidney injury and tell if their kidneys will continue functioning for the rest of their lives or fail in six months,” Dr. Kellum said. “But making that determination is important for properly counseling patients. A low-risk patient might need to simply avoid certain medications, while a higher-risk patient will need close medical attention.”
Dr. Kellum and his team used data from the Protocolized Care for Early Septic Shock (ProCESS) trial, which enrolled critically ill patients with septic shock in the U.S. Nearly 1,000 patients in the ProCESS trial were tested with the only test approved by the U.S. Food and Drug Administration (FDA) for acute kidney injury, NephroCheck, which measures two urinary biomarkers and returns a score meant to help determine a patient’s risk for acute kidney injury, not the extent of their damage or their outcome after they have the condition.
The team compared the test results to the patient outcomes and determined that patients with the same stage of acute kidney injury but with a higher NephroCheck value were more likely to die in the next six months than those with a lower score. In other words, a patient with only stage 1 (mild) acute kidney injury actually has a prognosis like a patient with stage 2 (moderate) injury if the test returns a positive biomarker. Conversely, a biomarker-negative stage 1 patient has a prognosis similar to no kidney injury at all.
Dr. Kellum noted that the results of his group’s analysis aren’t enough to immediately change testing guidelines or convince the FDA to revise the test’s label to be used for prognosis, but it was enough for him and his colleagues to begin designing future trials.
“Our findings provide pretty good evidence that biomarkers can augment staging of acute kidney injury and have sparked further work to see whether these markers are the best ones and what cut-offs we should use to assign a score,” Dr. Kellum said. “Ultimately, this work is imperative for public health. By properly treating acute kidney injury, we can preserve kidney function and protect other organs, preventing the need for dialysis, transplant, or death in the long run.”
AWARDS AND RECOGNITION
Dr. Anne Robertson Promoted to Distinguished Service Professor
Recognizing her contributions and service in support of teaching and research, as well as her development of a holistic mentorship program for new faculty, the University of Pittsburgh promoted McGowan Institute for Regenerative Medicine affiliated faculty member Anne Robertson, PhD, to Distinguished Service Professor, the highest honor that the University can accord a member of the professorate.
Dr. Robertson, a William Kepler Whiteford Professor of Engineering, holds a primary appointment in the Swanson School of Engineering’s Department of Mechanical Engineering and Materials Science (MEMS) with a secondary in Bioengineering, is nationally recognized for her research in hemodynamics, cerebral vascular disease, and the formation and treatment of intracranial aneurysms.
“I cannot be more excited for Anne and her promotion to the highest faculty rank at Pitt, joining an elite rank of individuals in our department and school,” said Brian Gleeson, PhD, the Harry S. Tack Chair Professor and MEMS Department Chair, who nominated Dr. Robertson for the position.
Dr. Robertson is also founding director of the Swanson School’s Center for Faculty Excellence, which helps newly recruited assistant professors navigate the teaching, research, scholarship, and support systems of the university environment. Young professors are mentored by a committee of interdisciplinary senior faculty from throughout Pitt as well as from Carnegie Mellon University. The Center aims to shepherd new faculty through their new tenure, improve retention, and encourage self-growth.
“I am deeply appreciative of the opportunities and support I have had to pursue initiatives in research and service at Pitt, while maintaining my engagement in classroom teaching,” she said. “It has been a privilege and inspiration to work with our outstanding junior faculty at Pitt through the Center for Faculty Excellence and gratifying to see the selfless commitment of my colleagues to mentoring these faculty across department, school, and even university lines.
“The University of Pittsburgh has been my academic home since I completed my postdoctoral training and so it is particularly meaningful to me to be promoted to the level of Distinguished Professor.”
Dr. Valerian Kagan Is the ‘Cover Scientist’ of Antioxidants and Redox Signaling
McGowan Institute for Regenerative Medicine affiliated faculty member Valerian Kagan, PhD, DSc (pictured), professor of environmental and occupational health at the University of Pittsburgh School of Public Health, was honored as the “cover scientist” of the journal, Antioxidants and Redox Signaling, for his pioneering work in the field of redox biology.
In addition to gracing the cover of the premier journal’s May issue, Dr. Kagan’s life and scientific achievements are the subject of a biographical article in the journal.
“Professor Kagan’s story is that of a quintessential scientist from the start. Always a doubter, but one working diligently to find the truth. The world of redox lipidomics, of which he is a major founder, is vastly richer for his contributions to these truths,” said Sally Wenzel, MD, chair of Pitt Public Health’s Department of Environmental and Occupational Health.
Illustration: Antioxidants & Redox Signaling.
Dr. Hēth Turnquist Received AST Basic Science Investigator Award
Congratulations to McGowan Institute for Regenerative Medicine affiliated faculty member Hēth Turnquist, PhD (pictured), associate professor in the University of Pittsburgh School of Medicine, Department of Surgery, Thomas E. Starzl Transplantation Institute, with a secondary appointment in the Department of Immunology, who received the 2022 AST Basic Science Investigator Award. AST, the American Society of Transplantation, is dedicated to advancing the field of transplantation and improving patient care by promoting research, education, advocacy, organ donation, and service to the community. Dr. Turnquist received this award as a mid-career investigator who has made substantial contributions to the field of transplantation medicine. He received this recognition during the AST Awards Ceremony during the American Transplant Congress in Boston, Massachusetts, on Sunday, June 5th.
Dr. Turnquist’s current research focus is Cytokine and Regulatory Cell Networks in Transplantation. Transplantation of genetically dissimilar (allogeneic) cells, organs, and composite tissues is a transformative procedure used to prolong and improve quality of life. Yet, these foreign materials initiate alloreactive immune responses. These pathogenic immune responses mediate destruction of transplanted tissues or alternatively, attack host tissues. The present answer to combat alloimmunity is global immune suppression, which is only partially effective and associated with morbidity- and mortality-causing toxicities and complications. Research in the Turnquist Lab aims to elucidate novel endogenous immunoregulatory mechanisms that can benefit transplant recipients by providing alternatives to non-specific immunosuppressants.
Congratulations Dr. Turnquist!
Dr. Steffi Oesterreich Named a Komen Scholar
The Susan G. Komen organization added nine researchers and two patient advocates as Komen Scholars. Among them is McGowan Institute for Regenerative Medicine affiliated faculty member Steffi Oesterreich, PhD, a leading UPMC Hillman breast cancer researcher, scientific collaborator, and co-director of the Women’s Cancer Research Center, a collaboration between UPMC Hillman and Magee-Womens Research Institute. The Komen Scholars are the foremost experts in laboratory research, clinical practice, public health, and patient advocacy. Adrian Lee, PhD, also a leading breast cancer researcher at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine, will join the Komen Scientific Advisory Board to help lead Komen’s overall research strategy and investments. Drs. Oesterreich and Lee will join an advisory group of nearly 50 accomplished leaders in breast cancer research and advocacy, representing more than 20 major health institutions across the U.S.
The Lee/Oesterreich Laboratory studies the molecular basis of breast cancer development and resistance to therapy with the goal of improving precision medicine and outcomes for breast cancer patients.
Dr. Oesterreich has authored over 160 scientific articles in breast cancer, and her research has continuously been funded by Susan G. Komen, Breast Cancer Research Foundation, the National Cancer Institute, and other sources. Both Dr. Oesterreich and Dr. Lee received the PNC Elsie Hillman Distinguished Scholar Award.
Congratulations, Drs. Oesterreich and Lee!
Dr. Thomas Rando Receives Prestigious NOMIS Foundation Award to Study Stem Cell Quiescence
Thomas Rando, MD, PhD, director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and an affiliated faculty member of the McGowan Institute for Regenerative Medicine, has received the NOMIS Foundation’s Distinguished Scientist and Scholar Award.
The five-year award will support Dr. Rando’s research into the molecular regulation of stem cell quiescence—a state in which a cell is not actively dividing but has retained the capacity to resume proliferating in response to certain stimuli.
“For many years, quiescence was viewed as a relatively unimportant state during which cells are inactive,” Dr. Rando said. “We have only recently discovered that quiescent stem cells are like the proverbial still waters that run deep. Quiescence is a complex and highly regulated state that is critical to the long-term survival and availability of the stem cell populations our bodies rely on throughout our lives.”
The focus of Dr. Rando’s NOMIS-funded project is to explore the hidden secrets of the quiescent state—how it adapts to environmental shifts, how it changes as a result of aging and how cellular decisions are made to either maintain quiescence or break quiescence and divide. The ultimate aim of these studies is to inform the development of new methods to promote stem cell resilience and thus enhance tissue maintenance and repair across the lifespan.
“I am deeply grateful and honored for the NOMIS Foundation’s recognition and support,” said Dr. Rando, who is also a professor of neurology at the David Geffen School of Medicine and of molecular, cell and developmental biology. “In addition to the potential clinical impact, this award will enable my lab to shed light on the trade-off between survival and reproduction, an interplay that is at the very core of the evolution of species.”
Dr. Rando is a renowned neurologist and stem cell biologist whose research has yielded critical insights into stem cell function and tissue repair. His laboratory’s groundbreaking studies in mice found that old tissues could be rejuvenated by exposure to young blood. This work has formed the basis of an expanding area of aging research and led to clinical trials of novel therapies for Alzheimer’s disease and other neurodegenerative conditions.
NOMIS is a private Swiss foundation that aims to catalyze scientific and human progress by supporting pioneering investigators, establishing collaborative research networks, and creating optimal conditions for the advancement of high-risk basic research. Dr. Rando will be presented his award at a ceremony in Zurich, Switzerland, in October 2022.
Regenerative Medicine Podcast Update
The Regenerative Medicine Podcasts remain a popular web destination. Informative and entertaining, these are the most recent interviews:
#234 –– Dr. Antonio D’Amore discusses his research in cardiovascular tissue engineering and his decision to become a U.S. citizen.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
PUBLICATION OF THE MONTH
Author: Luca Molinari; Gaspar Del Rio-Pertuz; Ali Smith; Douglas P. Landsittel; Kai Singbartl; Paul M. Palevsky; Lakhmir S. Chawla; David T. Huang; Donald M. Yealy; Derek C. Angus; John A. Kellum; for the ProCESS and ProGReSS-AKI Investigators
Title: Utility of Biomarkers for Sepsis-Associated Acute Kidney Injury Staging
Summary: Importance: The 23rd Acute Disease Quality Initiative (ADQI-23) consensus conference proposed a framework to integrate biomarkers into the staging of acute kidney injury (AKI). It is unknown whether tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulinlike growth factor binding protein 7 (IGFBP7) could be used for staging.
Objective: To test whether higher levels of urinary [TIMP-2] × [IGFBP7] are associated with lower survival among patients with the same functional stage of AKI.
Design, Setting, and Participants: This cohort study was performed using data from the Protocolized Care for Early Septic Shock (ProCESS) trial, which enrolled critically ill patients with septic shock who presented at academic and community emergency departments and intensive care units in the US from March 2008 to May 2013. Patients with end-stage kidney disease, a reference serum creatinine level of 4 mg/dL or greater (to convert to μmol/L, multiply by 76.25), or missing data on serum creatinine levels or urinary levels of [TIMP-2] × [IGFBP7] were excluded. Data were analyzed from October 2020 to October 2021.
Exposures: The presence of AKI, assessed using Kidney Disease: Improving Global Outcomes criteria within 24 hours after enrollment and the highest AKI stage as well as urinary [TIMP-2] × [IGFBP7] level at 6 hours after enrollment. A previously reported high-specificity cutoff level for [TIMP-2] × [IGFBP7] of 2.0 (ng/mL)2/1000 was used to categorize patients (including those without functional criteria of AKI) according to the new staging system proposed by the ADQI-23 as biomarker negative (urinary [TIMP-2] × [IGFBP7] level ≤2.0 [ng/mL]2/1000) or biomarker positive ([TIMP-2] × [IGFBP7] >2.0 [ng/mL]2/1000).
Main Outcomes and Measures: Survival (assessed using Kaplan-Meier plots and the log-rank test) and mortality (assessed using relative risk [RR] 30 days after enrollment).
Results: The analysis included 999 patients with a median age of 61 years (IQR, 50-73 years); 554 (55.5%) were male. Biomarker-positive patients had lower survival and higher mortality at 30 days in the groups with AKI stage 1 (RR, 2.20; 95% CI, 1.02-4.72), stage 2 (RR, 1.53; 95% CI, 1.04-2.27), and stage 3 (RR, 1.61; 95% CI, 1.00-2.60). The associations were specific to patients with AKI. No difference in 30-day survival was found between biomarker-positive and biomarker-negative patients in the absence of functional criteria for AKI (RR, 1.16; 95% CI, 0.45-3.01).
Conclusions and Relevance: The findings suggest that assessment of the cell-cycle arrest biomarkers TIMP-2 and IGFBP7 may augment AKI staging for patients with functional criteria for AKI.
GRANT OF THE MONTH
PI: Mohammad Eslami and David Vorp
Title: Endovascular Orifice Detection (EOrD) Device for In Situ Fenestration of Abdominal Aortic Aneurysm
Description: Abdominal aortic aneurysm (AAA) is a localized dilatation of the aorta and if left untreated may go on to rupture which is associated with a 90% mortality rate. This is the 15th leading cause of death in the United States with more than 15,000 deaths reported annually. When an aneurysm reaches the maximum diameter criteria (greater than 5.0 – 5.5 cm), clinicians will intervene with either open surgery or endovascular repair (EVAR). For complex AAA cases, a minimally invasive fenestrated EVAR (FEVAR) is preferred over high-risk open surgery, however, fenestrated stent-grafts extend past the visceral arteries (renal, superior mesenteric artery and celiac artery) and must be revascularized after deployment requiring the stent-graft to be prefabricated. Currently, there is only one FDA-approved fenestrated graft on the market, the Cook Zenith Graft, that requires additional imaging for fabrication with a 6 – 8 week delivery time, costs up to 3 times more than traditional EVAR stent-grafts, and can be technically challenging when passing guidewires through the orifices of the fenestrations. The objective of this project is to develop a medical device for endovascular orifice detection (EOrD) which will both locate visceral arteries and perform in situ fenestration. This device can then be applied in the cases of AAA, ascending aneurysms, and traumatic aortic injury. Preliminary in vitro experiments were performed to determine whether visceral arteries could be detected through chelated sheep blood and stent-graft material using infrared (IR) waves. A scaled-up sensor array was built using phototransistors along with an analog to digital converter to detect the reflected IR waves. Distinct signal responses were collected while sweeping the sensor array over the orifice of the visceral artery, confirming feasibility. After an orifice of the visceral artery is detected, we plan to create a fenestration using a low-powered laser or mechanical puncturing mechanism that simultaneously inserts a guidewire to deploy the bridging stents. Our initial EOrD prototype with the proposed approach will be delivered through a catheter sheath and tested for orifice detection, puncture, and guidewire insertion using realistic in vitro AAA phantoms and cadavers. Continuous feedback from our clinical experts will improve design iterations to develop a final prototype that is able to reliably and reproducibly perform in situ fenestration of stent-grafts to treat aortic aneurysms. With our novel device, we can improve patient healthcare and reduce overall costs associated with AAA repair.
Source: National Heart, Lung, and Blood Institute
Term: April 20, 2022 – March 31, 2024
Amount: $183,375 (one year)