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.
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.
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.
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.
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.
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.
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.
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:
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
In an effort to solve some of healthcare’s toughest challenges through the innovative use of technology, the University of Pittsburgh Medical Center (UPMC) Enterprises announced recently that it will fund several projects created under the umbrella of the Pittsburgh Health Data Alliance. Announced in March 2015, the Pittsburgh Health Data Alliance is a unique collaboration among UPMC, the University of Pittsburgh, and Carnegie Mellon University. It will focus on building new companies that create data-intensive software and services, with the potential to revolutionize health care and wellness.
McGowan Institute for Regenerative Medicine affiliated faculty member 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, is the co-author of a paper currently being published by Biomaterials. The title of the paper is “ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate.”
McGowan Institute for Regenerative Medicine faculty member Fabrisia Ambrosio, PhD, is an Associate Professor in the Department of Physical Medicine & Rehabilitation at the University of Pittsburgh. She holds secondary appointments in the Departments of Physical Therapy, Orthopaedic Surgery, and Microbiology & Molecular Genetics. In addition, she is a faculty member of the neurology residency program in the Department of Physical Therapy. Recently, Dr. Ambrosio and colleagues were awarded two NIH awards. Details on each follow:
A team of surgeons and interventional cardiologists at the University of Pittsburgh Medical Center (UPMC) recently performed their 500th transcatheter aortic valve replacement (TAVR), more than any other heart program in the region. The minimally invasive procedure repairs the aortic valve in patients with severe aortic stenosis, a debilitating narrowing of the heart’s aortic valve that causes shortness of breath, lightheadedness, and fatigue.
As reported by John Tozzi of Bloomberg Business, when McGowan Institute for Regenerative Medicine affiliated faculty member and Carnegie Mellon University (CMU) biomedical engineer Adam Feinberg, PhD, tried to figure out how to synthesize human tissue 4 years ago, his supplies were prosaic: a kitchen blender, some gelatin packets from the supermarket baking aisle, and a $2,000 3D printer.
“The original collaboration between Michael and myself was targeted at an entirely different technology and clinical issue, where we essentially stumbled upon the potential to create a biocompatible adhesive,” said Dr. Beckman, the George M. Bevier Professor of Engineering in Pitt’s Swanson School of Engineering. “Clinicians have lacked internal adhesives that are both strong and safe, and it’s exciting that TissuGlu was the first internal tissue adhesive to be approved by the FDA.”
The experiments, described ahead of print in the journal Regenerative Medicine, bring researchers closer to creating an implantable intestine as replacement therapy for a range of devastating disorders – including infections, cancer, and trauma – that result in loss or death of gut tissue. Chief among them is a condition that affects 12 percent of premature newborns, called necrotizing enterocolitis (NEC), which is marked by the rapid death of intestinal cells and permanent loss of intestinal tissue.
McGowan Institute for Regenerative Medicine affiliated faculty members Ipsita Banerjee, PhD, associate professor of chemical and petroleum engineering and of bioengineering within the University of Pittsburgh’s Swanson School of Engineering, and co-investigator Prashant Kumta, PhD, professor of bioengineering in the Swanson School, recently received a $300,000 grant from the National Science Foundation to explore an idea they have that would allow the manufacture of human pluripotent stem cells—these are the ones that can become virtually any tissue—on an industrial scale.
The new strategy combines two experimental techniques for reviving heart tissue after a heart attack. One approach is to inject a scaffolding material to reinforce the weakened muscle wall. Another is to inject stem cells or growth factors to help repair the damaged tissue. On their own, these individual methods have shown limited success in clinical trials.
Dr. Rocky Tuan, Co-Director of the Armed Forces Institute of Regenerative Medicine (AFIRM), the Department of Defense funded national, multi-institutional consortium, recently hosted a visit of the Department of Defense Regenerative Medicine Traveling Exchange program (TEP) to the University of Pittsburgh. This one day visit consisted of an overview of active AFIRM research projects being conducted at Pitt as well as presentations by Dr. Arthur Levine and Dr. Steven Shapiro representing the School of Medicine and UPMC, respectively. The TEP aims to enhance the interaction between research-minded military physicians and researchers of leading academic health centers of the nation involved in AFIRM in areas that are of relevance to military medicine. AFIRM presenters included Dr. Stephen Badylak, Dr. William Wagner, Dr. Peter Rubin, Dr. Kacey Marra and Dr. Rocky Tuan. Dr. Yoram Vodovotz and Dr. Vijay Gorantla presented on trauma-related research, including collaborative projects with the Walter Reed National Military Medical Center (WRNMC) and the Army Institute for Surgical Research (AISR). Drs. Tuan and Wagner also introduced the TEP visitors to the activities of Pitt’s Center for Military Medicine Research and the McGowan Institute for Regenerative Medicine. TEP Fellows attending included: LCDR Matthew Bradley (Assistant Professor, Uniformed Services University of the Health Sciences); Lt. Col Megan Burgess (San Antonio Military Medical Center (SAMMC) Center); LCDR Daniel Grabo (Navy Trauma Training Center, LAC+USC Medical Center); COL Booker King (Brooke Army Medical Center, San Antonio, TX); and LTC John Oh (Chief, General Surgery Services, Walter Reed National Military Medical Center). Representing the DoD: Dr. Wendy Dean, John Getz and Lt Col Melinda Eaton.
Co-led by McGowan Institute for Regenerative Medicine faculty members Stephen Badylak, DVM, PhD, MD, Professor in the Department of Surgery, a Deputy Director of the McGowan Institute, and Director of the Center for Pre-Clinical Tissue Engineering within the Institute, and 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, the research team uses extracellular matrix (ECM) from a pig’s bladder to regenerate diminished skeletal muscle. ECM is the remaining tissue after all the cells have been removed from the pig’s bladder. Dr. Badylak has been researching the effects of ECM since 1987. This study is the first to utilize ECM to replace and regenerate muscle tissue.
Textbook: Host Response to Biomaterials
The McGowan Institute for Regenerative Medicine is proud to recognize the efforts of Stephen Badylak, DVM, PhD, MD, professor in the Department of Surgery, a deputy director of the McGowan Institute, and director of the Center for Pre-Clinical Tissue Engineering within the Institute, as editor of the recently published textbook entitled “Host Response to Biomaterials,” which has been published by the Elsevier Academic Press.
