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Multi-disciplinary Research in Biology and Medicine
Richard E. Swaja, Ph. D.
Senior Science Advisor
National Institute of Biomedical Imaging and Bioengineering
National Institutes of Health
8:30-9:30

Abstract: Dramatic improvements in healthcare and quality of life have resulted from research and development that applied principles and methods from the quantitative sciences to address biomedical problems. As medical care continues to progress, research at spatial and temporal scales not encompassed by traditional biomedical disciplines is necessary to create significant advances. Biomedical research communities are well aware of the need to encourage and support multi-disciplinary approaches to research and development - approaches that will result from collaborations among disciplines and organizations. The National Institutes of Health (NIH) has developed opportunities and programs to facilitate and support disciplinary and organizational partnerships aimed at improving healthcare and medicine. This presentation discusses several of these programs and related opportunities for research funding. Programs that support the application of physical and engineering sciences to biology and medicine are described along with trans-NIH opportunities through the Bioengineering Consortium and Bioinformatics Consortium. Implications to investigators of the NIH Roadmap Initiative on multidisciplinary research and public/private partnerships is also discussed.

Biography: Dr. Richard E. Swaja is the Senior Science Advisor for the National Institute for Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH). His current responsibilities include developing research, training, and communication programs for the NIBIB; coordinating the NIH’s Bioengineering Consortium (BECON); coordinating trans-NIH and inter-agency biomedical research and training programs; and serving as scientific liaison to universities, private industry, and other Federal agencies. Prior to this position, Dr. Swaja was the Senior Advisor for Biomedical Engineering in the Office of Extramural Research at the NIH. Before coming to the NIH, he conducted and directed research and development programs in nuclear medicine, environmental pollutant detection and assessment, computational modeling and simulation, photonics, and radiobiology at the Oak Ridge National Laboratory. Dr. Swaja received the Ph.D. degree in Nuclear Science from Carnegie Mellon University in 1973.

Drug Delivery Technology Applied to the Drug Development Process
Terry K. Wiernas, Ph.D., M.B.A. R.Ph.
Senior Director Development, Pharmaceutical Products
Alcon Research, Ltd.
9:45-10:45

Abstract: Loss of vision is a very frightening prospect for most people since it is so integrally linked to overall independence. Alcon has been dedicated to developing and commercializing specialized pharmaceutical, surgical and consumer products that prevent the loss of vision or restore visual function for more than 50 years. This presentation will cover the basics of the drug discovery and drug development process. Specific examples will be presented of the application of drug delivery technology to improve product life cycles and enhance patient compliance. Greater collaboration between engineers and pharmaceutical scientists could easily result in tremendous advances in drug delivery for the future benefit of patients and physicians.

Biography: Dr. Terry K. Wiernas is a Senior Director, Development, Pharmaceutical Products at Alcon Research, Ltd. in Fort Worth, TX. Her current responsibilities include global product development of drugs to treat allergy, dry eye and inflammation, as well as surgical therapeutics, generics and product support. Prior to assuming this position, Dr. Wiernas served as a regulatory affairs executive responsible for both domestic and international registration of drug products. Before joining Alcon Research, she managed drug registrations for Whitby Research, Inc. and the A.H. Robins Co. in Richmond, Virginia. Dr. Wiernas began her career as a pharmacist in Biopharmaceutics Research at A.H.Robins Co. with responsibility for conducting research associated with product and process development of controlled-release dosage forms. Dr. Wiernas received her B.S. in Pharmacy from the Medical College of Virginia, M.B.A. from Virginia Commonwealth University and Ph.D. from the University of North Texas Health Science Center in Fort Worth.

Drug Delivery Fibers for Potential Solid Tumor Treatment
Kevin D. Nelson (1), Brent B. Crow (1), Deepal Panchal (1), Joana Ganter (2), Jason Fleming (3)
(1) Joint Program in Biomedical Engineering at The University of Texas Southwestern Medical Center at Dallas and The University of Texas at Arlington
(2) Universidade Federal do Parana - Curitiba - Brazil
(3) The University of Texas Southwestern Medical Center at Dallas
11:00-12:00

Abstract: A major segment of the research done in drug delivery uses biodegradable polymers that are loaded with drugs for slow, sustained release. These polymers usually have the format of microspheres with a diameter on the order of 10’s to 100 um. Several years ago, our lab developed the patent-pending method of extruding similar sized, drug-loaded, biodegradable fibers at room temperature that will slowly release drugs. These fibers have a number of important advantages over traditional microspheres such as continuous as opposed to batch processing, much smaller surface to volume ratio for a slower release, the ability of the fiber to have mechanical strength (i.e., you can tie knots in it), it is surgically removable, and it can hold a much larger drug load on a drug mass to polymer mass basis than the microspheres used by most researchers. In addition, these fibers can be made into different formats (e.g. they can be monofilament, hollow, water-filled, gel-filled, multi-layer core-in-sheath, etc.). Each of these formats provides a unique capability not found in other types of drug delivery modalities and provides a ready opportunity to combine different types of polymer in the same fiber. Each type of polymer can have different degradation rates, hence different drug release rates, and each can be loaded with a different drug. Therefore, this technology makes possible the delivery of different drugs, each with its own release kinetics from the same fiber.

We report here the results of a gel-filled fiber, wherein the gel was loaded with a beta-galactosidase adenovirus. This virus contains genetic material, which if infected within a cell will induce the creation of a protein that can be uniquely stained blue. Therefore, the extent of cell transfection can be readily identified. These fibers were surgically implanted into a human pancreatic tumor cell line that was implanted into immune-compromised mice. These tumors were allowed to grow to a size of approximately 5 mm in diameter before our fibers were implanted. The end result is that at the time of sacrifice, the tumors had nearly all cells within 2-4mm of the fiber turn blue, indicating that the virus successfully was loaded and released from the fiber with retained biological activity. This now provides hope that therapeutic viruses can also be loaded into our fibers with the end result being regression of a pancreatic tumor.

Biography: Kevin Nelson is an associate professor in the Joint Program of Biomedical Engineering at The University of Texas Southwestern Medical Center at Dallas and The University of Texas at Arlington. He is also the Founder, President and Chief Scientific Officer of TissueGen, Inc., a small company whose goal is to commercialize the intellectual property generated in his university labs.

Dr. Nelson has been doing research in the areas of drug delivery and tissue engineering since 1996. Dr. Nelson completed his doctorate degree in biomedical engineering in 1995 at The University of Texas Southwestern Medical Center at Dallas. Prior to this he worked as a mechanical engineer at General Dynamics, San Diego, CA as a structural dynamics engineer.

Abstract: Aging and chronic diseases such as diabetes result in problem wounds with impaired healing characteristics. These result in long term suffering, prolonged hospitalizations, amputations and can be life threatening. Approximately 15 years ago efforts began to bring together areas of biotechnology and tissue engineering to develop new technologies and alternatives to address these problems. A great deal has been learned since then especially in the areas of tissue growth factors and in methods for growing and manufacturing “ tissue equivalents” which may be used for treatment of such problem wounds. However, development of clinically useful technologies and products has been slow. Only a few such products are emerging on the market and the numbers of amputations required from problem wounds of diabetes continues to increase. This presentation provides an overview of the biotechnology and tissue engineering advances, current approaches, limitations and barriers, and potential new directions.

Biography: Dr. Gracy received his B.S. in Chemistry and Biological Sciences from California Polytechnic University and his Ph.D. in Biochemistry from the University of California. He was a Fellow of the Daymon Runyon Cancer Foundation at the Albert Einstein College of Medicine in New York City and a Fellow of the Alexander von Humboldt Foundation of Germany. In addition to his academic appointment as Professor of Molecular Biology he has served as Chairman of Biochemistry and Dean of Research. He has held Visiting Professor positions in Würzburg, Germany, Nanjing, China, Chiang Mai, Thailand, U.S. Virgin Islands and Puerto Rico.

Dr. Gracy's research focuses on the oxidative damage, proteomics and molecular basis for the accumulation of modified proteins in aging and such consequences as Alzheimer’s Disease. He was the recipient of Research Career Development and MERIT awards from the National Institutes of Health and research awards from the American Chemical Society and the American Osteopathic Medical Association (Gutensohn-Denslow Award). He has published approximately two hundred research papers and book chapters and holds several patents in biotechnology. Dr. Gracy was appointed by the Governor to serve on the Texas Healthcare Information Council and on the Texas Council on Science and Biotechnology Development. Dr. Gracy serves as a consultant to the pharmaceutical and biotechnology industries and is on the scientific advisory board and board of directors of several such industries.

Rotary Bioreactors: A New Tool for Tissue Engineering
Dr. Stephen S. Navran
Chief Scientist, Synthecon, Inc.
Adjunct Assistant Professor, Department of Medicine
Baylor College of Medicine
2:25-3:10

Abstract: The original concept of the Rotary Cell Culture System (RCCS) developed at NASA’s Johnson Space Center was to simulate the microgravity conditions of space in order to model at the cellular level the effects of microgravity on the astronauts. The principal used is to culture cells in a fluid-filled, zero headspace cylindrical chamber rotated horizontally to suspend cells in a continuous state of free fall with very low shear stress (< 0.5 dynes/sq. cm). Oxygenation is accomplished by diffusion through a silicone membrane on the back of the culture vessel or running down the center. During the initial testing of the bioreactor, it was observed that when dispersed cells were introduced into the vessel, they tended to aggregate and form large three-dimensional structures that resembled the tissues from which they were derived. Since then, a number of studies have confirmed that assembling cells in three-dimensional structures using the RCCS technology produced tissue analogs that were functionally very close to intact tissues both at the cellular and molecular level. For basic science, the advantages of this technology are obvious. For therapeutics, the possibilities for using the RCCS for tissue engineering are vast. The development of the RCCS has continued from its original concept of a simple rotating fluid-filled cylinder. For example, we now have continuously perfused systems that better maintain normal physiological conditions than the original batch culture devices. Nevertheless, there are a number of areas in which engineering disciplines can interface with biology to impact this technology:

1. Fluid Mechanics: Aggregation of cells is very sensitive to the movement of the surrounding fluid. If there is too little aggregation, cells may undergo apoptosis (programmed cell death). If there is too much aggregation, cells in the center of the aggregates will die from lack of oxygen and nutrients. Analysis of the effect of the shape of the culture vessel on the behavior of cells cultured in the RCCS is needed.

2. Biomaterials: Most cells in the body exist in a complex extracellular matrix environment which profoundly influences gene expression and tissue function. The ability to synthesize materials which mimic the extracellular matrix will be very important for producing tissues for therapeutic applications.

3. Sensors and control systems: In the body, the tissue environment is maintained within very narrow limits. In cell culture systems, especially batch culture, the environment can vary tremendously, causing stress to the cells. By developing compact, robust sensors and control systems for the RCCS, it will be possible to reduce tissue injury and improve the quality of the tissue-engineered product.

Biography: I did my doctoral work at the Ohio State University in Biochemical Pharmacology. My thesis involved the biochemistry and pharmacology of platelet aggregation. After finishing at Ohio State, I did a post-doctoral fellowship at Baylor College of Medicine in the Cardiovascular Sciences Section of the Department of Medicine. My work involved the role of the sodium/potassium pump in vascular contractility and smooth muscle growth. At the end of my post-doctoral fellowship I joined the facility in Cardiovascular Sciences and studied the regulation of vascular smooth muscle by adrenergic receptors. During my time at Baylor, I had an opportunity to visit NASA engineers and scientists who were developing what they called the Rotating Wall Vessel. When two of the developers left NASA to form Synthecon to commercialize the system which is now known as the Rotary Cell Culture System (RCCS), I joined them to help develop new applications.

Interdisciplinary Solutions to Problems in Tissue Engineering
S. Dan Dimitrijevich, Ph.D.
Director, Laboratories of Human Cell & Tissue Engineering
University of North Texas Health Science Center
3:20-4:05

Abstract: Development and function of living organisms involve biomechanical events arising primarily form interactions of cellular components with the extracellular matrix, the major component of living organisms. These interactions, now recognized as mechano-signaling, transmitted by the cellular cytoskeleton, culminate in gene expression changes. Such mutual dependence is reflected in unique organization of a number of tissues that is essential for their function. Thus an understanding of normal state and pathological conditions of tissues demands multidisciplinary approaches that are particularly evident in tissue engineering.

Our involvement in mechanical aspects of tissue biology began with the construction of 3-dimensional in vitro models of human tissue–Tissue Equivalents. This “Tissue Engineering” concept incorporates normal human cells into collagen type I architecture to produce living models the skin and the cornea. The unique properties of our design are optical translucency and dimensional stability. Translucency allows observation of cellular morphology, movement, and viability by variety of methods. The consequence of dimensional stability Tissue Equivalents a perfect model for studies of tissue contraction, which ideally closes a wound, but when poorly controlled, result in debilitating scar formation.

Measurement of tissue contraction and direct real time observations of cellular events are examples of challenges requiring engineering approaches. Similarly the challenge of constructing highly organized tissue such as the cornea or vascular wall are examples of future interdisciplinary challenges.

Biography: Educated in UK, [BSc. (Applied Chemistry); Ph.D. (Carbohydrate Synthesis), Bath University, Bath UK]. Postdoctoral experience shared between pharmaceutical (Institute of Molecular Biology Syntex Research, Palo Alto CA., and Nucleic Acid Research Institute, ICN Pharmaceuticals, Irvine, CA) and academic research (University of Alberta, Edmonton Canada; Durham University, Durham UK; University of London Berkbeck College, London, UK; State University of New York, Buffalo NY).

Joined UNT Health Science Center in 1987, and changed research interest to biological aspects of wound healing/tissue repair, which evolved into human cell and tissue engineering. Dr Dimitrijevich has been Acting Director of the Wound Healing Research Institute and Director of Human Cell and Tissue Engineering Laboratories associated with The Eye Research Institute and Cardiovascular Research Institute. He has several patents in the tissue engineering area and is a consultant and a member of Scientific Advisory Boards for several established pharmaceutical companies and emerging biotech companies.

Engineering Implications of Understanding Human Accommodation
Ronald A. Schachar, M.D., Ph.D.
Adjunct Professor of Physics
University of Texas at Arlington
4 :15-5:00

Abstract: Accommodation is the dynamic ability of the eye to change focus. It occurs as a result of changes in the surface curvatures of the crystalline lens. The force from ciliary muscle contraction is transduced by the zonules to the equator of the lens to induce the required lenticular surface changes. The ciliary muscle is approximately one tenth the size of the crystalline lens and can only generate a total force of 1.6 grams. The mechanism by which this small muscle can produce accommodation has significant practical implications.

Biography: Dr. Schachar earned a Ph.D. in Ophthalmology from the University of Chicago in 1975, an M.D. from the State University of New York in 1967, and a B.S. in Physics from the City University of New York in 1963. Dr. Schachar holds 64 international patents and has authored over 100 archival journal articles and 7 books in the field of ophthalmology. He is the founder of the Presby Corporation. From 1998 to 2002, he raised over $13 million for funding of the Presby Corporation. From 1998 to 2001, the Presby Corporation, under Dr. Schachar’s guidance, generated $4 million in revenues. In 2003, the Presby Corporation merged into Refocus Group, Incorporated. Today, Dr. Schachar serves as a consultant to the Presby Corporation and is an Adjunct Professor in the Department of Physics at the University of Texas at Arlington, Texas.