BME Seminar
Functional Tissue Engineering for Tendon Repair: Stimulating Stem Cell-Collagen Scaffold Constructs with Mechanical and Biological Signals
All dates for this event occur in the past.
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Room 145 Mount Hall
1050 Carmack Road
Columbus, OH 43210
United States
Biomedical Engineering Seminar
Thursday 11/18/2010, 4-5PM
Mount Hall (West Campus), Room 145
"Functional Tissue Engineering for Tendon Repair: Stimulating Stem Cell-Collagen Scaffold Constructs with Mechanical and Biological Signals"
by
David L. Butler, PhD
Professor, Department of Biomedical Engineering
University of Cincinnati
Abstract:
Achilles and rotator cuff tendon injuries and tendon graft reconstructions remain frequent and complex musculoskeletal problems. Using a functional tissue engineering approach, our group has been improving adult rabbit patellar tendon repair using tissue engineered constructs (TECs) containing autologous mesenchymal stem cells (MSCs) in collagen-based scaffolds. Inserting these TECs into central PT defects significantly improves not only their failure properties but their stiffness in the functional range of in vivo loading. Mechanically stimulating these constructs in culture also improves both TEC and repair stiffness. The strong correlation between both measures indicates that certain in vitro mechanical parameters might actually predict in vivo outcome and that optimizing stiffness in culture could further enhance soft tissue repair. Recently, we have also been using developmental biology to improve patellar tendon repair across multiple species. By monitoring changes in local murine gene expression during development, we hope to identify developmental cues and signaling pathways controlling tenogenesis. This data could lead to growth factor cocktails that stimulate cell-based TECs and repairs in both the rabbit and ovine models. In this regard, we have developed double transgenic reporter mouse strains in which cells transcribing Col1 and Col2 genes express cytoplasmic GFP and cytoplasmic ECFP-cyan, respectively. We have used these murine models to also develop a unique Col2 transgenic rabbit. We now seek to create spatial and temporal “maps” of expression within the developing tendon as benchmarks for effective healing and repair of adult PT injuries across species. Ultimately, we hope to determine how normal tendon development coupled with mesenchymal stem cell therapy could be used to truly regenerate tendon after injury.
Biographical Information: David L. Butler
Dr. David L. Butler is currently Professor of Biomedical Engineering in the College of Engineering at the University of Cincinnati. After receiving his Ph.D. in Engineering Mechanics and Biomechanics from Michigan State University, he joined the University of Cincinnati in 1976. His research in the Departments of Orthopaedic Surgery and Aerospace Engineering and Engineering Mechanics focused on ligament and tendon biomechanics and in vivo function as well as methods to more effectively repair and replace injured soft tissues. In 1988, he received both the Kappa Delta Young Investigator Award, the highest research award given by the American Academy of Orthopaedic Surgeons, and the Gustas Larson Award from the American Society of Mechanical Engineers (ASME). He was also the 1990 recipient of the Sigma Xi Award at UC. In 1995, Dr. Butler became a fellow of ASME and an inaugural fellow of the American Institute of Medical and Biological Engineers. In 1996, he established collaborations with colleagues at Case Western Reserve University and Osiris Therapeutics to develop research expertise using autologous mesenchymal stem cells to enhance tendon repair. His laboratory is now pursuing methods to optimize 3-D tissue engineering repair through control of cell density, scaffold selection and environmental stimulation as well as knowledge of gene expression during growth and development. In 2001, he helped to found the Department of Biomedical Engineering at UC and served as Principal Investigator of a Whitaker Foundation Special Opportunity Award to create the graduate program for BME. In 2007, Dr. Butler and his team received a second Kappa Delta Research Award from AAOS in the area of tendon repair using mesenchymal stem cells and mechanical stimulation. He is funded by three NIH R01 grants (two as PI) including a recent Bioengineering Research Partnership Grant with Cincinnati Children’s Hospital. He has over 130 peer-reviewed publications in biomechanics and tissue engineering and has just recently stepped down as a permanent member of Musculoskeletal Tissue Engineering Study Section of the National Institutes of Health. Currently Chair of the US National Committee on Biomechanics, Dr. Butler is helping to develop policy and research direction in biomechanics at the national level. He is also leading efforts to establish success criteria for musculoskeletal tissue repair and replacement, having just completed a consensus conference with surgeons, biologists and biomaterial scientists from industry, government and academia. The published white paper is helping to guide universities, government labs and industry as they seek to perform basic research and develop novel tissue engineering therapies for damaged and diseased musculoskeletal tissues.