Tissue Engineering

Just as a climbing plant needs the right trellis to thrive, a small-diameter tissue-engineered vascular graft (TEVG) needs the right scaffold to transform seeded cells into a native-like artery that can save a life.

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As a Senior Staff Writer for Orthopedics Today, Ms. Casey Tingle recently reviewed the impact of artificial intelligence (AI) in the health care sector.  In her article she highlighted where AI may provide benefits to patients with musculoskeletal injuries.  Her work included input from McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor of surgery at the University of Pittsburgh, who said AI may be able to identify whether tissues that are healing from a traumatic injury will have a good or bad outcome based on certain biomarkers.

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McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor of surgery at the University of Pittsburgh, is an inventor of 71 U.S. patents and over 300 patents worldwide. In August 2020, Dr. Badylak received two new patents relative to his work with extracellular matrix (ECM).  They are:

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Researchers from Sechenov University and the University of Pittsburgh compared the properties of two groups of extracellular vesicles. Either present in a liquid phase or attached to the fibers of the extracellular matrix, these vesicles facilitate metabolism and cell-cell communication. A better understanding of their structure, production and movement can help create new bioengineered materials and repair damaged tissues more quickly.

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Brain tissue lost after a stroke is not regenerated, although a repair response associated with neurogenesis does occur. A failure to regenerate functional brain tissue is not caused by the lack of available neural cells, but rather the absence of structural support to permit a repopulation of the lesion cavity. Inductive bioscaffolds can provide this support and promote the invasion of host cells into the tissue void.¹

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As the Baby Boomer generation gets older, the number of Americans over 65 continues to grow. With this growth, there is a need for improved medical technology that will help clinicians more effectively treat common age-associated conditions such as heart disease — a leading cause of death in the U.S.

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University of Pittsburgh School of Medicine researchers have created a biodegradable nerve guide — a polymer tube — filled with growth-promoting protein that can regenerate long sections of damaged nerves, without the need for transplanting stem cells or a donor nerve.

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Some of the most challenging medical conditions are acute brain injury and progressive neurodegenerative disease.  Aiming to examine these issues, Frontiers in Neuroscience recently published the review article entitled “Bioscaffold-Induced Brain Tissue Regeneration” by Michel Modo, PhD, Professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition.

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Researchers from Carnegie Mellon University (CMU) have published a paper in Science that details a new technique to 3D bioprint tissue scaffolds out of collagen, the major structural protein in the human body. This first-of-its-kind method brings the field of tissue engineering one step closer to being able to 3D print a full-sized organ such as an adult human heart.  The work was done in the lab of Adam Feinberg, PhD, a professor of biomedical engineering (BME) and materials science & engineering at CMU.  Dr. Feinberg is an affiliated faculty member of the McGowan Institute for Regenerative Medicine.

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The McGowan Institute has formed an alliance with the International Space Station (ISS) U.S. National Laboratory to develop and demonstrate how microgravity can improve regenerative medicine-based therapies. The ISS provides a unique platform to conduct studies in a microgravity environment.

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McGowan Institute for Regenerative Medicine faculty member Fabrisia Ambrosio, PhD, MPT, Director of Rehabilitation for UPMC International and Associate Professor in the Department of Physical Medicine & Rehabilitation at the University of Pittsburgh with secondary appointments in the Departments of Physical Therapy, Bioengineering, Orthopaedic Surgery, and Microbiology & Molecular Genetics, and Carnegie Mellon University’s Philip LeDuc, PhD, William J. Brown Professor of Mechanical Engineering with appointments in Biological Sciences, Computational Biology, and Biomedical Engineering, the Founding Director of the Center for the Mechanics and Engineering of Cellular Systems, and a McGowan Institute affiliated faculty member, are the co-principal investigators on a recently awarded National Institutes of Health R01 grant entitled “Role of Extracellular Matrix in Age-Related Declines of Muscle Regeneration.”

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McGowan Institute for Regenerative Medicine affiliated faculty member Thomas Rando, MD, PhD, professor, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, and California and Florida researchers recently developed a two-pronged method that makes mouse leg muscles regrow better. Their research was recently published in Communications Biology.

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Starfish can repair injured arms and reptiles can regrow severed tails; from bacteria to humans, every species is capable of regeneration, albeit to variable extents. These functions help make species more resilient, but how can we apply the knowledge of these regenerative mechanisms to improve human health? The University of Pittsburgh Department of Bioengineering has been collaboratively working to address this question through research efforts in tissue engineering and regenerative medicine.

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In a major medical breakthrough, Tel Aviv University (TAU) researchers have ‘printed’ the world’s first 3D vascularized engineered heart using a patient’s own cells and biological materials.  The engineered heart completely matches the immunological, cellular, biochemical and anatomical properties of the patient.

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In the lab of McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor of surgery, University of Pittsburgh, and director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute, the major focus is the development of regenerative medicine strategies for tissue and organ replacement. The utilization of mammalian extracellular matrix (ECM), or its derivatives, as an inductive template for constructive remodeling of tissue is a common theme of most research activities.

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Lizards can regrow an entire tail and salamanders can regrow a leg. Unfortunately, our human bodies mainly just close wounds and make scar tissue. But just imagine the possibilities if we could grow a new limb after an amputation or a new organ, rather than needing a transplant?  That is the focus of a recent interview by Julie Rose, BYU Radio, with McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor in the Department of Surgery and director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute.

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Peripheral nerve matrix (PNM) is an injectable gel derived from porcine tissue that promotes and supports repair and regeneration in injured peripheral nerves. PNM technology is based on 4 years of research in the laboratory of McGowan Institute for Regenerative Medicine faculty member Bryan Brown, PhD, Assistant Professor in the Department of Bioengineering with secondary appointments in the Department of Obstetrics, Gynecology, and Reproductive Sciences and the Clinical and Translational Science Institute at the University of Pittsburgh, and the laboratory of McGowan Institute affiliated faculty member Jonathan Cheetham, VetMB, Diplomate ACVS, PhD, Associate Professor of Clinical Sciences at Cornell University.  PNM is the first product for Renerva, LLC, a Pittsburgh-based medical device company developing innovative technology for peripheral nerve injuries. PNM is protected by five patents licensed from the University of Pittsburgh and Cornell University.

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ECM Therapeutics, Inc. has licensed multiple extracellular matrix (ECM) technologies developed in the laboratory of Stephen Badylak, DVM, PhD, MD (pictured top), including hydrogels, bioactive derivatives and methods for delivering these materials within the body. Dr. Badylak is a professor in the Department of Surgery, a deputy director of the McGowan Institute for Regenerative Medicine, and the director of the Center for Pre-Clinical Tissue Engineering within the Institute.

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Extracellular matrix (ECM) hydrogel promotes tissue regeneration in many peripheral soft tissues. However, the brain has generally been considered to lack the potential for tissue regeneration.  In their study published in Acta Biomaterialia, McGowan Institute for Regenerative Medicine affiliated faculty member Michel Modo, PhD, Professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition, and McGowan Institute Deputy Director Stephen Badylak, DVM, PhD, MD, Professor in the Department of Surgery at the University of Pittsburgh and Director of the Center for Pre-Clinical Tissue Engineering within the Institute, demonstrated that tissue regeneration in the brain can be achieved using implantation of ECM hydrogel into a tissue cavity. They and the research team further demonstrated that a structure-function relationship is key to promote tissue regeneration in the brain.  This approach offers new avenues for the future treatment of chronic tissue damage caused by stroke and other acute brain injuries.

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From the desk of McGowan Institute for Regenerative Medicine faculty member J. Peter Rubin, MD, UPMC Endowed Professor and Chair of Plastic Surgery, Director, UPMC Wound Healing Services, Professor of Bioengineering, University of Pittsburgh:

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Platelet-rich plasma (PRP) is believed to provide pain relief and help improve joint function in degenerative joint disease, but a new study—coauthored by McGowan Institute for Regenerative Medicine affiliated faculty member Rocky Tuan, PhD, Vice-Chancellor and President of The Chinese University of Hong Kong—has shown that it does not act by promoting stem cell proliferation or enhance the cartilage formation capabilities of mesenchymal stem cells (MSCs). The effects of PRP treatment on cartilage formation and chondrogenesis in the presence of adult human MSCs derived from two different sources are reported in the study published in Tissue Engineering, Part A, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

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When an institution encourages the free flow of ideas and doesn’t rigidly define the roles of its researchers, new and better solutions are the result. And free-thinking scientists are the sort of people who are attracted to a collaborative environment that encourages risk-taking. These are the enironments where ideas are grown.

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McGowan Institute for Regenerative Medicine congratulates George Hussey, PhD, and Jenna Dziki, PhD student, on their newly published Nature Reviews Materials article entitled, “Extracellular matrix-based materials for regenerative medicine.” It is featured on the cover of the July 2018 issue of the journal with a 3D image of the matrix network by Visuals Unlimited, Inc./Dr. Edna Cukierman.

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LyGenesis, Inc., a biotechnology company developing innovative technology for organ regeneration, announced recently that they have raised $3 million in Series A financing from Juvenescence, Ltd.  LyGenesis’ technology uses lymph nodes as bioreactors to regrow functioning organs within a patient’s own body. The financing will enable LyGenesis to complete the final preclinical work required to enable human clinical trials, which will initially focus on patients with end stage liver disease.

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Per the United Network for Organ Sharing, every ten minutes, someone is added to the national transplant waiting list in need of a kidney, liver, pancreas, heart, lung, or intestine, the most needed organs of 2017.  As of the end of January 2018, there were 114,883 people needing a lifesaving organ transplant (total waiting list candidates) with 74,722 of those people being active waiting list candidates.  Tragically, on average, 20 people die each day while waiting for a transplant.  More than 7,000 candidates died in 2016 while on the wait list, or within 30 days of leaving the list for personal or medical reasons, without receiving an organ transplant.

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When a patient with heart disease is in need of a vascular graft but doesn’t have any viable veins or arteries in his or her own body, surgeons can rely on synthetic, tissue-engineering grafts. However, the body often treats these substitutes as a threat and rejects them. Researchers at the University of Pittsburgh are developing synthetic grafts that mimic the body’s own blood vessels to mitigate many of the complications of bypass surgery.

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Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation
Michelle L. Ratay, Elena Bellotti, Riccardo Gottardi, and Steven R. Little
Advanced Healthcare Materials; 2017 Dec;6(23).

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As reported by Dan Mohler for the University of Pittsburgh’s Innovation Institute, from the beginning, McGowan Institute for Regenerative Medicine faculty member Bryan Brown, PhD, Assistant Professor of Bioengineering, recognized that the nerve repair technology he was developing addressed an unmet clinical need.

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McGowan Institute for Regenerative Medicine affiliated faculty member Julie Phillippi, PhD, Assistant Professor in the Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, received NIH funding for her project entitled “Matrix mediated vasa vasorum dysfunction in thoracic aortic disease.”  The funding period is August 2017 through June 2022.  The total award is $1,901,221.

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The research of McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, was center stage at this year’s World Science Festival held in New York City.  Dr. Badylak, professor in the Department of Surgery at the University of Pittsburgh School of Medicine and director of the Center for Pre-Clinical Tissue Engineering within the Institute, participated in the panel discussion entitled “Forever Young: The Promise of Human Regeneration.”  The program began with a video of Marine Sergeant Brian Smith, a clinical trial participant in the study entitled, “Musculotendinous Tissue Repair Unit and Reinforcement (MTURR).” The primary objective of the study was to assess mechanical strength and function in patients undergoing musculotendinous tissue unit repair and reinforcement with the use of biologic scaffolds for the restoration of both mechanical strength and function in these patients.  The results of the study were reported in July 2016 in npj Regenerative Medicine.

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The work of McGowan Institute for Regenerative Medicine director William Wagner, PhD, and colleagues is featured on the cover of the May 15, 2017, issue of the publication, Journal of Surgical Research.  The corresponding article is entitled “Use of a pedicled omental flap to reduce inflammation and vascularize an abdominal wall patch.”  The co-authors are Takafumi Uchibori, MD; Keisuke Takanari, MD, PhD; Ryotaro Hashizume, MD, PhD; Nicholas J. Amoroso, PhD; and Yuzuru Kamei, MD, PhD.

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Extracellular matrix (ECM) represents the structural and functional molecules secreted by the resident cells of every tissue in the body. Researchers in the laboratory of Stephen Badylak, DVM, PhD, MD, Professor in the University of Pittsburgh’s Department of Surgery, a deputy director of the McGowan Institute for Regenerative Medicine, and Director of the Center for Pre-Clinical Tissue Engineering within the Institute, have extensive experience isolating and harvesting this ECM and producing usable formats for use in pre-clinical animal and bench top studies. Scientists routinely produce ECM from tissue such as small intestine, urinary bladder, and liver tissue. The cells of these tissues are removed by physical, enzymatic, and/or chemical methods so that only the native ECM remains.

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The National Institute of General Medical Sciences (NIGMS) awarded principal investigator Bryan Brown, PhD, Assistant Professor in the Departments of Bioengineering and Obstetrics, Gynecology, and Reproductive Sciences and faculty member at the McGowan Institute for Regenerative Medicine, a 5-year R01 award for his work entitled “Assessing the Impact of Macrophage Polarization Upon the Success of Biomaterial Implants.”  Co-investigators on this project include McGowan Institute affiliated faculty members Pamela Moalli, MD, PhD, Associate Professor, Departments of Obstetrics, Gynecology, and Reproductive Sciences and Bioengineering, and Stephen Badylak, DVM, PhD, MD, Professor in the Department of Surgery, deputy director of the McGowan Institute, and Director of the Center for Pre-Clinical Tissue Engineering within the Institute.

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Many lower forms of life on earth exhibit an extraordinary ability to regenerate tissue, limbs, and even organs—a skill that is lost among humans and other mammals. Now, a University of Pittsburgh researcher has used the components of the cellular “scaffolding” of a zebrafish to regenerate heart tissues in mammals, specifically mice, as well as exhibiting promising results in human heart cells in vitro.

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The research efforts of McGowan Institute for Regenerative Medicine affiliated faculty members Michel Modo, PhD, associate professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition, and Stephen Badylak, DVM, PhD, MD, a deputy director of the McGowan Institute, professor in the Department of Surgery, and director of the Center for Pre-Clinical Tissue Engineering within the Institute, were recently published in the journal, Biomaterials.  Their paper is entitled “Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.”  This study was funded by a seed grant from the Department of Health of the Commonwealth of Pennsylvania (4100068505) and the National Institute for Neurological Disease and Stroke (R01NS08226).

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Results of a study recently published online in the Journal of Crohn’s and Colitis provided positive results from the assessment of the effectiveness of a hydrogel for the treatment of Inflammatory Bowel Disease (“IBD”).   The study was led by McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, in collaboration with Asana Medical, Inc.  The study focused on effectiveness of an ExtraCellular Matrix Hydrogel (“ECMH”) in the treatment of IBD.  Asana has a field-limited exclusive license to certain patent rights for this technology from the University of Pittsburgh.

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A study from the McGowan Institute for Regenerative Medicine identifies a mechanism by which bioscaffolds used in regenerative medicine influence cellular behavior, a question that has remained unanswered since the technology was first developed several decades ago. The findings were recently published online in Science Advances.

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Results of a study conducted by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine showed significant improvement in strength and range of motion, as well as evidence for skeletal muscle regeneration, in 13 patients who were surgically implanted with bioscaffolds derived from pig tissue to treat muscle injuries. The patients had failed to respond to conventional treatment before use of the extracellular matrix (ECM). The findings were published online in npj Regenerative Medicine.

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The therapeutic use of human cell and tissue products is highly regulated by the U.S. government, but a specific exception allows surgeons to harvest, manipulate, and implant tissues in many commonly performed surgical procedures. While the operating room is often the stage where innovations in tissue engineering and regenerative medicine are realized, as surgeons use grafted tissues, novel biomaterials, and new approaches to numerous procedures including performing breast, chest and abdominal wall, and pelvic floor reconstruction, new FDA draft guidelines would place even tighter restrictions on surgical practice and may limit the development of new therapies. This topic is examined in an Editorial in Tissue Engineering, Part A, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.  The article is available free for download on the Tissue Engineering website until July 1, 2016.  McGowan Institute for Regenerative Medicine faculty member J. Peter Rubin, MD, Chair of the Department of Plastic Surgery, UPMC Endowed Professor of Plastic Surgery, and Professor of Bioengineering at the University of Pittsburgh, is a co-author of the Editorial.

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Medical science and research has helped move many parts of cardiology from potentially fatal conditions to more chronic issues for patients and doctors to address. Cholesterol control is moving in that direction thanks to new advancements in medication and surgical options.

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