December 2011 | VOL. 10, NO. 12 | www.McGowan.pitt.edu
3-D Models to Prepare for Complex Face Transplants Created
By combining conventional medical imaging with some of the same 3-D modeling techniques used in Hollywood blockbusters, McGowan Institute for Regenerative Medicine affiliated faculty member Vijay Gorantla, MD, PhD, associate professor of surgery in the Department of Surgery, Division of Plastic Surgery at the University of Pittsburgh, and administrative medical director of the Reconstructive Transplant Program at UPMC, and colleagues at UPMC are reinventing how plastic surgeons prepare for complicated face transplant surgeries. Researchers with the Reconstructive Transplant Program have developed a new fused 3-D model that can be manipulated by surgeons to prepare for surgery.
"This surgery is for patients with devastating injuries to the face, who have lost their ability to smell, eat, and engage socially and have no other conventional treatment options," said Dr. Gorantla.
Because face transplantation surgery is medically complex, imaging plays a major role in selecting patients, planning donor and recipient surgery, and assessing postoperative motor and sensory function.
By combining information from multiple imaging exams and creating a sophisticated 3-D computer model, surgeons will be better able to assess the facial structure and contours, the underlying bone, muscles, nerves, and vessels, as well as the full extent of the damage of a face transplant candidate.
Using integrated information from different imaging exams of sample patients, including 3-D CT, CT angiography, MRI, and high-definition tractography, UPMC researchers developed a protocol for a 3-D model that shows a patient's head and neck anatomy. This same type of modeling technology often is used in movies to animate computer-generated characters with detailed three-dimensional human features and facial expressions. "While there have been some fusions of imaging techniques before, this is the first time anyone has combined so many imaging techniques in a user-friendly model that can be manipulated for detailed face transplant planning," said Darren Smith, M.D., resident, UPMC Division of Plastic and Reconstructive Surgery.
"We are integrating data from multiple imaging sources into a single 3-D representation that allows for real-time user interaction and modification," added Dr. Smith. "In assessing eligibility for face transplant surgery, it is critical to understand whether the patient has enough blood vessels and bone structure to support new facial tissue. This 3-D modeling will help us customize the procedure to the patient's individual anatomy so that the donor tissue will fit like a puzzle piece onto the patient's face."
Using this approach, the team overlaid the computerized patient model with a polygon mesh of a generic human face and customized it to the recipient's facial anatomy. Dr. Smith said the ability to manipulate this 3-D facial envelope allows the entire surgical team to participate in planning exactly where bone, blood vessel, and nerves will be cut and connected, as well as to evaluate the outcomes of reconstructive transplantation, including nerve regeneration within the transplanted tissues.
"The goal of face transplantation is not just structural," Dr. Gorantla said. "It is about restoring function, so that patients are once again able to chew their food, smile, and regain the most important aspect of a normal face — to look human."
The 11th Annual McGowan Institute for Regenerative Medicine Scientific Retreat is set to take place on March 4-7, 2012 at Nemacolin Woodlands Resort. The poster session will also begin on the evening of March 4, 2011, at which time there will be an informal mixer. Click here for registration information. Under the leadership of Dr. William Wagner, the program committee is planning an exciting group of speakers and topics. The program will include:
Distinguished Lecturer: Leonard Zon, MD-Harvard.
Working sessions will feature topics in the areas of Cell Therapy, Tissue Engineering, Medical Devices, and Computation and Modeling.
In addition to the outstanding scientific program, once again the Office of Enterprise Development (OED) is hosting the "Innovator Elevator Pitch." This event will consist of a series of scheduled brief presentations from participating faculty on the value of their technology to an audience which will include industry and venture capitalist participants. The audience will select the winner who will receive a $7,500 prize sponsored by OED. This event will be a great opportunity to present the clinical/commercial value of your work to industry participants who may be interested in exploring collaboration or licensing opportunities. Information regarding on-line registration is available here.
The McGowan Institute is pleased to announce the upcoming speakers for our Distinguished Lecture series. C. James Kirkpatrick, MD, PhD, DSc, FRCPath, FBSE is the Professor and Director of the Institute of Pathology, University Medical Center at Johannes Gutenberg University in Mainz, Germany. He will be speaking on February 23, 2012 at the University Club at 4pm, followed by a Moleculart networking reception. The topic of the lecture is to be announced. Simona Nemcova, RDMS, RVT of the Vascular Clinical & Translational Research Center at the University of Pittsburgh, will display her art at the reception.
Leonard Zon, MD, Grousbeck Professor of Pediatric Medicine at Harvard Medical School, Investigator at Howard Hughes Medical Institute, and Director of the Stem Cell Program, Children's Hospital Boston, will speak at the McGowan Institute Retreat on March 5, 2012 at Nemacolin Woodlands Resort. The topic of the lecture will be "Pathways Regulating Stem Cell Self-Renewal and Differentiation."
McGowan Institute for Regenerative Medicine faculty members Kacey Marra, PhD, associate professor, Department of Surgery, University of Pittsburgh, director, Plastic Surgery Laboratory, and co-director of the Adipose Stem Cell Center, and J. Peter Rubin, MD, chief of the Division of Plastic and Reconstructive Surgery, associate professor at the University of Pittsburgh, and co-director of the Adipose Stem Cell Center, are working with two Indiana-based engineering and life sciences companies to adapt a technology that holds promise to help soldiers regrow tissue and recover from severe wounds. IKOTECH, LLC and Techshot, Inc., based in Indiana, are working to develop equipment called Quadrasep™ that improves the collection of stem cells from adult adipose, or fat, tissue. The U.S. Army Medical Research and Materiel Command selected the companies for a $730,000 contract to develop the technology.
"Fat contains 10 times more stem cells than bone marrow," said Rich Boling, vice president of corporate advancement at Techshot. "When they are transplanted, stem cells have the potential to dramatically improve the outcomes of patients with significant tissue loss, such as soldiers who suffer severe wounds."
The process to harvest pure stem cells is done manually, and it is very time-consuming. A better purification method for isolating specific cells from fat has the potential to unleash a number of new cell therapies.
"The initial application for this technology is to help soldiers who have suffered trauma and wounds. The technology developed in this project should also lead to new treatments for conditions and diseases that will improve the quality of life for people around the world.
"Fat grafting, or moving fat tissue from one part of the body to another, has been used as a cosmetic procedure for decades," comments Dr. Rubin, "but we are now applying this technology for reconstructive surgery to accurately restore facial form after battlefield injuries." The use of fat grafting for serious facial injuries, such as those resulting from roadside bombs, is facilitated in the DOD Biomedical Translational Initiative project by specially designed devices and instruments for harvesting the fat tissue and implanting it into regions of scarred tissue.
University of Pittsburgh mathematicians have been collaborating with Pitt's School of Medicine to find ways to stop the symptoms of Parkinson's disease, thanks in part to a 4-year, $1.86 million grant from the National Science Foundation (NSF) and a 5-year $1.2 million grant from the National Institutes of Health (NIH). The NSF grant began in 2007 and has funded a number of research projects within Pitt's Department of Mathematics; the NIH grant is in its first year.
The team of Pitt mathematicians serving as co-principal investigators on the NSF award for the study of complex biological systems across multiple space and time scales includes McGowan Institute for Regenerative Medicine affiliated faculty members:
- Jonathan Rubin, PhD, professor, Department of Mathematics
- G. Bard Ermentrout, PhD, Distinguished University Professor of Computational Biology and professor, Department of Mathematics
- David Swigon, PhD, associate professor, Department of Mathematics
- Ivan Yotov, PhD, professor and chair, Department of Mathematics
The principal investigators of the NIH grant are Dr. Rubin and Pitt researchers Robert Turner, PhD, associate professor of neurobiology at Pitt, and Brent Doiron, PhD, assistant professor of mathematics.
The Pitt mathematicians, working with neurobiology researchers, are using computational models, experiments, and analysis of models and data to study the way that signals are transferred between the basal ganglia, a collection of nuclei found in the brain that helps with motor control, and the thalamus, its downstream target in the brain. Although scientists can't yet prevent the cell death associated with Parkinson's, their study of mathematical patterns could guide the development of less invasive treatments that block the motor symptoms of the disease. The research team is trying to understand the neuronal activity patterns so they can improve the deep brain stimulation procedure, making it more individualized and efficient.
Illustration: McGowan Institute for Regenerative Medicine.
McGowan Institute for Regenerative Medicine founding director Alan Russell, PhD, Distinguished University Professor, Department of Surgery, University of Pittsburgh, will serve as the first Editor-in-Chief of the recently announced, Disruptive Science and Technology. The new publication, scheduled to launch in 2012, is a highly innovative, bimonthly peer-reviewed journal that seeks to publish game-changing research that has the potential to significantly improve human health, well-being, and productivity. The journal will present new and innovative results, essential data, cutting-edge discoveries, thorough syntheses and analyses, and publish out-of-the-box concepts that will improve the way we live.
"Although much has been written about disruptive innovation and the business practices that can harness radical new ideas to change the course of history, there is no venue that has been designed to accelerate the pace at which enabling science and engineering will be developed to innovate disruptively," says Dr. Russell, professor in the Departments of Bioengineering, Chemical Engineering, and Rehabilitation Science and Technology, University of Pittsburgh. "This journal will provide a custom-designed forum for the publication of breakthrough science and engineering that has the capacity to dynamically improve our society."
Dr. Russell leads a multidisciplinary editorial team of opinion leaders and original thinkers in the scientific and business community including:
- Senior Executive Editor Clayton M. Christensen, Harvard Business School
- Executive Editor Aubrey de Grey, SENS Foundation
- Ray Kurzweil, Kurzweil Technologies
- Joseph Vacanti, Massachusetts General Hospital
- Philip Yeo, SPRING, Singapore
- Paul T. Anastas, Yale University
- Eric J. Beckman, University of Pittsburgh
- David Berry, Flagship Ventures
- Caro Elias, Wallace H. Coulter Foundation
- Jennifer Elisseeff, Johns Hopkins University
- Michael Goldblatt, Functional Genetics
- Dean Kamen, DEKA Research
- Takeo Kanade, Carnegie Mellon University
- Milan Mrksich, Northwestern University
- Mark Murcko, Boston, MA
- George Poste, Arizona State
- Richard Satava, University of Washington Medical Center
- Melissa Stark, Accenture
- Peter Thiel, Clarium Capital
Offering original articles accompanied by video and podcasts from the authors, Disruptive Science and Technology will provide an up-close-and-personal view into extraordinary discoveries presented by developing a direct relationship between reader and author. Readers can become participants in a unique multimedia platform that allows for dialogue among a community of top academic scientists, corporate innovators, business leaders, and futurists who provide unique and fascinating views on the science and technology that will shape our future.
"This year's Nobel prize winner in Chemistry told the world he could not publish his early work in world-class journals because it changed the paradigm of what was accepted," reports Mary Ann Liebert, President of Mary Ann Liebert, Inc., publishers. "Our new journal seeks to be the forum in which exceptional, paradigm-shifting research and development will be published in a world-class journal."
As Army leaders built the warrior care and transition program, they realized the need for a text to assist new unit leaders attending a 2-week course at Fort Sam Houston, Texas. This handbook, which was a year in the making, was recently published.
"Warrior Transition Leader -- Medical Rehabilitation Handbook," was co-edited by McGowan Institute for Regenerative Medicine affiliated faculty member Rory Cooper, PhD, FISA/PVA Endowed Chair and a Distinguished Professor of the Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Sciences, University of Pittsburgh, the Center Director at the Center of Excellence for Wheelchair and Related Technology, VA Rehabilitation Research & Development Center, and a Senior Research Career Scientist at the VA Rehabilitation Research and Development Service, U.S. Department of Veterans Affairs; Col. Paul Pasquina; and Ron Drach.
As they developed the first program, he said the nurse case managers, the squad leaders, the primary care physician, and all the other cadre and support team members built the Warrior Transition Units as they learned lessons about how best to support, heal, rehabilitate, and transition Soldiers and their families.
Dr. Cooper, lead editor, said the book also covers the history of the Warrior Transition Command, the history of AMEDD, explains the models of disability, how disability is defined, provides a little bit of history of the disability rights movement -- especially military-related, and then it defines the roles of the different healthcare professionals in medical rehabilitation.
The handbook also helps non-medical leaders to understand medications, medication interactions, risk factors for self-medication, suicide, traumatic brain injury, and polytrauma, to name a few.
To showcase the book, a 1-day course at the Uniformed Service University located at the Walter Reed National Military Medical Center provided participants with an overview of current medical techniques and programs to support leaders at Warrior Transition Units.
Presented by the University of Pittsburgh and Center for Rehabilitation Science Research at the Uniformed Services University of Health Sciences, this State of Science Symposium provided students with the latest strategies in treatment, rehabilitation, community reintegration, and full participation of people with disabilities.
Course directors were Dr. Cooper; Col. Paul Pasquina, director of the Center for Rehabilitation Sciences Research and chief of the Department of Orthopedics and Rehabilitation at WRNMMC in Bethesda; and McGowan Institute for Regenerative Medicine affiliated faculty member Michael L. Boninger, MD, professor and chair of the Department of Physical Medicine and Rehabilitation, associate dean for Medical Research, and professor at the School of Medicine, University of Pittsburgh and VA Rehab Research and Development Service.
AWARDS AND RECOGNITIONS
McGowan Institute for Regenerative Medicine affiliated faculty member David H. Perlmutter, MD, scientific director and physician-in-chief at Children's Hospital of Pittsburgh of UPMC and the Vira I. Heinz Professor and Chair of the Department of Pediatrics at the University of Pittsburgh School of Medicine, has received the 2011 Shwachman Award from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).
The Shwachman Award is given annually by NASPGHAN to an individual who has made major, lifelong scientific or educational contributions to the field of pediatric gastroenterology, hepatology, or nutrition in North America. Dr. Perlmutter received the award during NASPGHAN's annual meeting.
"Dr. Perlmutter has influenced the course of pediatric gastroenterology through his science, his leadership, and through his considerable effort as an advocate for research in childhood liver disease. He has made important contributions to the next generation of pediatric gastroenterologists, both directly through fellow education and indirectly as a role model for physician-scientists. Many of those touched by Dr. Perlmutter have made significant contributions to the field of pediatric gastroenterology," NASPGHAN noted.
Dr. Perlmutter earned his medical degree from St. Louis University School of Medicine and trained in pediatrics at The Children's Hospital of Philadelphia and in pediatric gastroenterology and nutrition at Children's Hospital Boston.
Dr. Perlmutter has made significant contributions in both clinical and basic science research of pediatric liver disease. He has carried out basic research on alpha-1-antitrypsin deficiency for more than 20 years. His work has led to many new concepts about the pathobiology of liver disease in this deficiency and has suggested several new concepts for chemoprophylaxis of chronic liver injury, hepatocellular carcinoma, and emphysema in this genetic disease. He is the principal investigator of three National Institutes of Health (NIH) R01 grants in this area and also now holds four other NIH grants, including the Child Health Research Center of Excellence Award for training pediatric physician-scientists in the molecular basis of pediatric disease.
Dr. Perlmutter's research has been widely recognized and has earned him many awards, including the AGA/Industry Research Scholar Award, the RJR Nabisco Research Scholars Award, the American Heart Association Established Investigator Award, the Burroughs-Wellcome Fund Scholar in Experimental Therapeutics Award, the E. Mead Johnson Award for Research in Pediatrics, and the Andrew Sass-Kortsak Award for Pediatric Liver Research.
Dr. Perlmutter is a member of the Institute of Medicine, the American Society for Clinical Investigation, and the Association of American Physicians. He has served as the president of the Society of Pediatric Research and is now a member of the Advisory Council of the National Institute for Diabetes, Digestive and Kidney Diseases and of the Scientific Advisory Council for the March of Dimes Foundation. He also is a member of numerous other advisory boards, foundation boards, and editorial boards. Since joining Children's Hospital in 2001, Dr. Perlmutter has led an effort to expand the hospital's basic and clinical research program so that it is ideally poised to investigate the molecular basis of disease and to develop innovative therapies. Children's Hospital is now one of the fastest growing pediatric research programs in the country in terms of NIH funding.
McGowan Institute for Regenerative Medicine affiliated faculty member Rory Cooper, PhD, Distinguished Professor and FISA-Paralyzed Veterans of America Chair in the Department of Rehabilitation Science and Technology in Pitt's School of Health and Rehabilitation Sciences, has been selected to receive the 2011 American Association for the Advancement of Science (AAAS) Mentor Award.
The award honors individuals who demonstrate extraordinary leadership in increasing the participation of underrepresented groups in science and engineering. During his time as a Pitt faculty member, Dr. Cooper has mentored nearly 100 undergraduate students, 69 master's degree students, 37 PhD degree students, and 17 postdoctoral fellows; half of these 200-plus students and fellows have come from underrepresented groups.
Dr. Cooper came to Pitt in 1994, founding the Human Engineering Research Laboratories. In 1999, the facility became the first, and remains the only, national VA Rehabilitation Research and Development Center of Excellence in Pennsylvania.
Dr. Cooper attended California Polytechnic State University, San Luis Obispo, where he earned both his bachelor's and master's degrees in electrical engineering. He earned his PhD in electrical and computer engineering from the University of California, Santa Barbara. He did his postgraduate fellowship at the VA Rehabilitation Research and Development Center in the Edward Hines Jr. Veterans Affairs Hospital in Hines, Illinois.
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Daly KA, Liu S, Agrawal V, Brown BN, Johnson SA, Medberry CJ, Badylak SF.
Damage associated molecular patterns within xenogeneic biologic scaffolds and their effects on host remodeling.
The immune response is an important determinant of the downstream remodeling of xenogeneic biologic scaffolds in vivo. Pro-inflammatory responses have been correlated with encapsulation and a foreign body reaction, while anti-inflammatory reactions are associated with constructive remodeling. However, the bioactive and bioinductive molecules within the extracellular matrix (ECM) that induce this polarization are unclear, although it is likely that cellular remnants such as damage associated molecular patterns (DAMPs) retained within the scaffold may play a role. The present study investigated the immunomodulatory effects of common ECM scaffolds. Results showed that tissue source, decellularization method and chemical crosslinking modifications affect the presence of the well characterized DAMP - HMGB1. In addition, these factors were correlated with differences in cell proliferation, death, secretion of the chemokines CCL2 and CCL4, and up regulation of the pro-inflammatory signaling receptor toll-like receptor 4 (TLR4). Inhibition of HMGB1 with glycyrrhizin increased the pro-inflammatory response, increasing cell death and up regulating chemokine and TLR4 mRNA expression. The present study suggests the importance of HMGB1 and other DAMPS as bioinductive molecules within the ECM scaffold. Identification and evaluation of other ECM bioactive molecules will be an area of future interest for new biomaterial development.
Biomaterials. 2012 Jan;33(1):91-101. Epub 2011 Oct 2.
|Co-PI||Alan Russell and Mark Yazer|
Continuous Red Blood Cell Production (Phase II)
07/01/11 - 06/30/12
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