November 2006 | VOL. 5, No 11 | www.McGowan.pitt.edu

McGowan Faculty Recognized by Scientific American

Two McGowan Institute researchers have been named by Scientific American magazine as research leaders within the 2006 Scientific American 50 [www.sciam.com]. The magazine’s prestigious annual list recognizing outstanding acts of leadership in science and technology from the past year includes the McGowan Institute’s William Wagner, PhD. and Michael Sacks, PhD

The work of Dr. Wagner and Dr. Sacks that forms the basis of this prestigious recognition is their development of novel biodegradable scaffolds. To view the article, please click here. Work related to this award is described in the paper “Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix” that was published in the journal Biomaterials (Volume 27, Issue 5, February 2006, Pages 735-744; available at www.sciencedirect.com).  This paper summarizes the fabrication of biodegradable elastomers by electrospinning.  The matrices that are formed resemble the scale and mechanical behavior of the native extracellular matrix. Dr. Wagner and his colleagues achieve high-cellular density and infiltration by electrospraying vascular smooth muscle cells (SMCs) concurrently with electrospinning a biodegradable, elastomeric poly(ester urethane)urea (PEUU).

In addition, the research described in the paper “Design and analysis of tissue engineering scaffolds that mimic soft tissue mechanical anisotropy” which was published in the journal Biomaterials (Volume 27, Issue 19, July 2006, Pages 3631-3638; available at www.sciencedirect.com) addresses the fact that tissue engineered constructs must exhibit tissue-like functional properties, including mechanical behavior comparable to the native tissues they are intended to replace. Moreover, the ability to reversibly undergo large strains to promote and guide tissue growth is realized with this new fabrication approach.

Electrospun poly (ester urethane) ureas (ES-PEUU) are elastomeric and allow for the control of fiber diameter, porosity, and degradation rate. ES-PEUU scaffolds can be fabricated to have a well-aligned fiber network, which is important for applications involving mechanically anisotropic soft tissues.  The researchers have developed ES-PEUU scaffolds under variable speed conditions and modeled the effects of fiber orientation on the macro-mechanical properties of the scaffold.

To illustrate the ability to simulate native tissue mechanical behavior, Drs. Wagner and Sacks demonstrated that the high velocity spun scaffolds exhibited highly anisotropic mechanical properties closely resembling the native pulmonary heart valve leaflet. Moreover, use of the present fiber-level structural constitutive model allows for the determination of electrospinning conditions to tailor ES-PEUU scaffolds for specific soft tissue applications. The results of these studies will help to provide the basis for rationally designed mechanically anisotropic soft tissue engineered implants.

Scientific American Editor-In-Chief John Rennie: “The Scientific American 50 pays tribute to individuals and organizations who, through their efforts in research, business and policy-making, are driving advances in science and technology that lay the groundwork for a better future. Not only does our list honor these prime movers – it shines a spotlight on the critical fields that are benefiting from their achievements.”

Past Scientific American 50 lists have spotlighted visionaries from an array of fields. Prior honorees have included Google founders Larry Page and Sergey Brin (sharing SA 50 2005 Business Leader of the Year); noted stem cell researcher Douglas A. Melton, Professor of the National Sciences at Harvard (2004 Policy Leader of the Year); Nobel prize-winning neurobiologist Roderick MacKinnon, Professor of Molecular Neurobiology and Biophysics of Rockefeller University (2003 Aerospace/Business Leader): global public health leader Gro Harlem Brundtland, former World Health Organization Secretary General (2003 Policy Leader of the Year); corporate chief Jeffrey Immelt, Chairman and CEO, General Electric Company (2002 General Technology/Business Leader).

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Professor Sacks-Next Technical Editor of Journal of Biomechanical Engineering

Professor Michael Sacks has been selected by the ASME Executive Committee of the Bioengineering Division to be the next Technical Editor of the Journal of Biomechanical Engineering, starting from July 1, 2007, for a five-year term.

The McGowan Institute offers our heartiest congratulations to Professor Sacks for this outstanding accomplishment which is in recognition of his international leadership in biomechanics research and education.

The Journal of Biomechanical Engineering reports research results involving the application of mechanical engineering knowledge, skills and principles to the conception, design, development, analysis, and operation of biomechanical systems, including: artificial organs and prostheses; bioinstrumentation and measurements; bio-heat transfer; biomaterials; biomechanics; bioprocess engineering; cellular mechanics; design and control of biological systems; and physiological systems.

Professor Sacks' research focus is quantification and modeling of the structure-mechanical properties of native and engineered soft tissues, with a focus on tissues of the cardiovascular and urological systems. In particular, his laboratory has focused on the mechanical behavior and function of the native aortic and mitral heart valves, including the development of the first constitutive (stress-strain) models for these tissues using a structural approach.

The Sacks laboratory is also active in the biomechanics of engineered tissues, and in particular understanding the in-vitro and in-vivo remodeling processes from a functional biomechanical perspective. To acquire the necessary critical experimental data, his laboratory has developed several novel methods to quantify tissue structure and multi-axial mechanical testing techniques. By integrating the resulting experimental data obtained from both techniques, the Sacks lab has developed structural constitutive (stress-strain) models that directly integrate information on tissue composition and structure. These models avoid ambiguities in material characterization, offering insight into the function, structure, and mechanics of tissue components.

More recent work includes multi-scale studies of cell/tissue/organ mechanical interactions in heart valves. I am particularly interested in determining the local stress environment for heart valve interstitial cells. Next, we are currently utilizing an integrated experimental/multi-scale finite element approach to determine how hemodynamic loading on the valve translates to altered stress states on the valve interstitial cell function and, in-turn, changes in local extra-cellular structure/composition and valve function.

Dr. Badylak on CNN

CNN on November 19, 2007 introduced a story on the needs of amputees and the prospects that in the future it may be possible to regenerate portions of lost limbs or digits.  Dr. Stephen Badylak of the McGowan Institute shares his insights and experiences with CNN host Miles O’Brien.  To see “Welcome to the Future- New Hope for Amputees”, please click here.
The work of Dr. Badylak and his colleagues across the Country is focused on learning how to regrow a mammalian digit. It’s a challenge Dr. Badylak, with the other participating scientists from across the United States, has accepted. The group received a $3.7-million, 12-month grant from the Department of Defense’s Defense Advanced Research Projects Agency (DARPA). The researchers hope their efforts will result in a mouse regenerating a functional digit—much in the same manner that a salamander or newt regenerates a limb. The grant could be worth up to $15 million throughout four years.
"We sincerely believe that the ability to promote tissue restoration in humans is not only possible, it will in fact be a reality some day. By working as a team and capitalizing on our collective expertise and experience, we're in a better position to succeed at unlocking the regenerative potential of mammals than would be possible working in the silos of our individual labs," said Dr. Badylak. The investigators believe their goal is attainable due to a convergence of recent discoveries made in their labs as well as at other institutions in the areas of stem cell research, extracellular matrix biochemistry and the regulation of gene expression.
The team consists of:

• Susan Braunhut, Ph.D., professor of biological sciences at the University of Massachusetts at Lowell

• Lorraine Gudas, Ph.D., chairman of the pharmacology department and Revlon Pharmaceutical Professor of Pharmacology and Toxicology, Weill Medical College of Cornell University, New York City

• Ellen Heber-Katz, Ph.D., professor, molecular and cellular oncogenesis program, The Wistar Institute in Philadelphia

• Shannon Odelberg, Ph.D., assistant professor, departments of internal medicine and neurobiology and anatomy, University of Utah, Salt Lake City

• Hans-Georg Simon, Ph.D., a developmental biologist and assistant professor of pediatrics, Children's Memorial Research Center and Northwestern University in Chicago

McGowan Institute Distinguished Lectureship

2007
January
11	Presenter: Art Coury, Ph.D. Vice President Biomaterials Research- Genzyme Topic: Tissue Engineering, Regenerative Medicine: Perceptions, Realities and Implications Abstract: As commonly reported in the public media and even among its practitioners, the field of tissue engineering is not thriving commercially.  Investment in tissue engineering ventures, market capitalization and staffing in United States corporations are claimed to have peaked around the year 2000.1 Most such start-ups reported in the 1990s have not survived in their original form.  These results have led to pessimistic evaluations of the field and its potential, which, unfortunately, are widely accepted currently.  Evaluation of these reports reveals a very narrow perception of tissue engineering (for example, involving cells in scaffolds). However, most definitions such as “Teaching the body to heal itself, achieved by the delivery to the appropriate site of cells, biomolecules and supporting structures.”2 allow a broad interpretation, which, in sum, provide for the systematic control of the body’s cells, matrices and fluids. This allows many profitable commercial products such as surgical sutures, staples, sealants and adhesives, wound dressings, adhesion prevention products, drug delivery systems and others to fall within its scope. In this interpretation, regenerative medicine comprises one component of tissue engineering.  Tissue engineering therapies are not all-inclusive.  Excluded from the definition are replacement devices such as orthopedic, cardiovascular, ophthalmic and dental products which command a large percentage of non-pharmaceutical therapeutic revenues.   However, by my estimate, some 20-30% percent of such revenues, approaching $50 billion in annual sales, can be attributed to tissue engineering, providing a much more positive picture of the field.  This interpretation, for which examples will be given for its justification, provides both psychological and economic value, encouraging investment in public, corporate and educational programs, and providing attractive career choices to assure future growth.  1Lysaght, M. et al, Tissue Engineering: 10(1), 2004, 309-320; 7(5), 2001, 485-493; 4(3), 1998, 231-238. 2 Williams, D. F., “The Williams Dictionary of Biomaterials,” Liverpool University Press, Liverpool, (1999). Location: Scaife Hall, Auditorium #5 Time: 4:00 to 5:00 PM
February
8	Presenter: Nicholas Peppas, Sc.D. -Fletcher Pratt Chair of Chemical Engineering, Biomedical Engineering and Pharmaceutics at the    University of Texas at Austin -Director of Center on Biomaterials, Drug Delivery, Bionanotechnology and Molecular  Recognition -Director of National Science Foundation Program on Cellular and Molecular Imaging for   Diagnostics and Therapeutics Topic: Nanostructured biomaterials and surfaces for biological recognition Abstract: Engineering the molecular design of intelligent biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. We address design and synthesis characteristics of artificial molecular structures capable of specific molecular recognition of biological molecules. Molecular imprinting and microimprinting techniques, which create stereo-specific three-dimensional binding cavities based on a biological compound of interest, can lead to preparation of biomimetic materials for intelligent drug delivery, drug targeting, and tissue engineering. We have been successful in synthesizing novel glucose- and protein-binding molecules based on non-covalent directed interactions formed via molecular imprinting techniques within aqueous media. Location: Scaife Hall, Auditorium #5 Time: 4:00 to 5:00 PM
April
12	Presenter: Professor Catherine Kielty Royal Society Wolfson Professor Faculty of Life Sciences University of Manchester, Manchester, UK Topic: TBA Location: Scaife Hall, Auditorium #5 Time: 4:00 to 5:00 PM

For Additional Information, please click here

Dr. DeKosky on the Latest Clinical Advances for Alzheimer’s

Steven T. DeKosky, M.D., professor and chair of the department of neurology and director of the Alzheimer’s Disease Research Center at the University of Pittsburgh, presented the latest information on Alzheimer’s disease at a recent community lecture (Nov. 21, 2006).

Dr. DeKosky’s clinical research includes investigations into improved methods and technologies for diagnosing, imaging and determining genetic risks for Alzheimer’s disease. He currently is director of a national multicenter trial to assess whether the herbal supplement Ginkgo biloba can delay the onset of dementia in elderly adults. He also is a leading researcher in the area of identifying structural and neurochemical changes in the brains of people with dementia as well as those changes that occur with normal aging.

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REGENERATIVE MEDICINE PODCASTS

The Regenerative Medicine Podcasts continue to be well received. There have been over 4,700 downloads to date. The most recent podcasts are:

#22- Dr. Doros Platika Technology transfer is an important step in moving new concepts from the lab to the marketplace. Until December 1, 2006 Doros Platika, M.D. has served as the President and Chief Executive Officer of the Pittsburgh Life Sciences Greenhouse which is a is a public/private partnership that invests in and supports the growth of life sciences companies in the areas of: bioinformatics; bionanotechnology; diagnostics; medical devices; medical robotics; therapeutics; and tools and services in the Pittsburgh region. Effective December 1, 2006, Dr. Platika has embarked on a new role: helping to get funding to study the world's oldest people.  Dr. Platika is the chairman of the Supercentenarian Research Foundation, a new organization designed to pump funding into studies that look at why supercentenarians, or people who have lived more than 110 years, have survived as long as they have. In podcast #22 Dr. Platika reviews the accomplishments of the Pittsburgh Life Sciences Greenhouse and his vision for the Supercentenarian Research Foundation. #21- Shelley Zomak and Judi Vensak Organ transplantation is a magnificent display both of medicine and the human spirit: The achievements of people who have received new hearts and other organs are truly amazing. Many of those triumphs are showcased in the U.S. Transplant Games, a biennial, Olympic-style athletic contest organized by the National Kidney Foundation. Events include swimming, table tennis, golf, basketball, track and field, tennis, bowling, racquetball, and volleyball. In podcast #21 Shelley Zomak and Judi Vensak, share their introduction to the Transplant Games, their experiences at the 2006 games, and tell us what to expect from the 2008 Transplant Games, which are expected to bring more than 7,000 observers and 1,400 athletes to Pittsburgh (July 11-16, 2008). Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.

MOLECULAR ART NETWORKING SESSIONS

Based on the requests of faculty and graduate students for more and different types of networking sessions, the Moleculart project will continue in the Fall term. Our goal is to have a scientific gathering that fosters networking in a different environment. Please save the date and join us on December 6th;

• December 6, 2006
  Artist: Laura Backman
  Time: 4:30 – 6:30 PM
  Place: S-100 BST

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MCGOWAN INSTITUTE RETREAT-PLEASE SAVE THE DATE

On-Line Registration Will Be Available in January

McGowan Institute - 2007 Scientific Retreat
March 5 and 6, 2007

Nemacolin Woodlands Resort - Farmington, PA

PUBLICATION OF THE MONTH

Publication of the Month | November 2006
Author(s)	John J. Stankus, Jianjun Guan, Kazuro Fujimoto and William R. Wagner
Title	Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix
Summary	Electrospinning permits fabrication of biodegradable elastomers into matrices that can resemble the scale and mechanical behavior of the native extracellular matrix. However, achieving high-cellular density and infiltration with this technique remains challenging and time consuming. We have overcome this limitation by electrospraying vascular smooth muscle cells (SMCs) concurrently with electrospinning a biodegradable, elastomeric poly(ester urethane)urea (PEUU). Trypan blue staining revealed no significant decrease in cell viability from the fabrication process and electrosprayed SMCs spread and proliferated similar to control unprocessed SMCs. The resulting SMC microintegrated PEUU constructs were cultured under static conditions or transmural perfusion. Higher cell numbers resulted with perfusion culture with 131% and 98% more viable cells versus static culture at days 4 and 7 (p<0.05). Fluorescent imaging and hematoxylin and eosin staining further illustrated high cell densities integrated between the elastomeric fibers after perfusion culture. SMC microintegrated PEUU was strong, flexible and anisotropic with tensile strengths ranging from 2.0 to 6.5 MPa and breaking strains from 850 to 1700% dependent on the material axis. The ability to microintegrate smooth muscle or other cell types into a biodegradable elastomer fiber matrix embodies a novel tissue engineering approach that could be applied to fabricate high cell density elastic tissue mimetics, blood vessels or other cardiovascular tissues.
Source	Biomaterials, Volume 27, Issue 5, February 2006, Pages 735-744

GRANT OF THE MONTH

Grant of the Month | November 2006
PI	David Vorp, PhD
Co-PIs	Michael Chancellor, MD; Douglas Chew, BS; Johnny Huard, PhD; Naoki Yoshimura, MD, PhD
Title	Bioengineered Urethral Augmentation
Description	Urethral dysfunction is a common complication of diabetes mellitus, spinal cord injury and pelvic trauma. Stress urinary incontinence (SUI) - the involuntary loss of urine secondary to a damaged urethral sphincter mechanism - is particularly common in women and can result from vaginal childbirth. There are currently several approaches to treat SUI, all of which are limited by ineffectiveness or subsequent complications. Regenerative medicine approaches, including cell therapy and tissue engineering, could potentially address these limitations. We believe that utilization of a functional tissue engineered urethral wrap (TEUW) will allow the native urethra to remain intact, while providing enhanced mechanical stability and functional reinforcement through designed regenerative repair mechanisms. We will explore the use of progenitor cells as the functional component of a TEUW. Specifically, we will explore the following two hypotheses: a living, functional, smooth muscle-populated tubular construct can be fabricated in-vitro by appropriately stimulating bone marrow derived progenitor cells (BMPCs) within a natural biological matrix; and a tissue engineered urethral wrap (TEUW) derived from these constructs can be successfully implanted and will reverse the short-term changes in mechanical and functional properties of the urethra found in a rat model of SUI. We propose two specific aims to explore these hypotheses. AIM 1 is to fabricate a living, functional smooth muscle populated tubular construct from BMPCs and a natural biological matrix that is suitable for implantation as a TEUW. This will be determined by determining the in-vitro stimulation regimen, chosen from a cadre of combinations of mechanical strain and biochemicals that yield optimal histological, functional, biomechanical and immunological properties. AIM 2 is to assess a TEUW composed of the BMPC-derived SMC-populated constructs from specific aim 1. Assessments will include both in vitro and in vivo analyses, using histological, functional, biomechanical, and immunological endpoints. Results will be compared with normal and diseased native urethra, as well as a TEUW constructed using isolated native urethral SMCs. Successful development a TEUW for an insufficient urethral continence mechanism would potentially provide relief from SUI and other urethral disorders.
Source	NIH-R21
Term	2 Years