Engineered Tissues
Tuesday, April 10, 10:30-12:00, Minnesota Room, McNamara Alumni Center

Organizer: Robert T. Tranquillo, Professor and Department Head, Biomedical Engineering, University of Minnesota

"Next Generation Tissue Engineered Vascular Grafts" (10:30)
Christopher K. Breuer, MD, Associate Professor of Surgery (Pediatrics) and of Pediatrics, Director of Tissue Engineering, Yale School of Medicine

"In Vivo Remodeling of a Completely Biological Vascular Graft" (11:00)
Robert T. Tranquillo, PhD, Professor and Head, Department of Biomedical Engineering, University of Minnesota

"Tissue Engineering Lungs from Bone Marrow" (11:20)
Angela Panoskaltsis-Mortari, PhD, D (ABMLI), Pediatric BMT and Pulmonary Medicine, University of Minnesota

"Biomimetic Extracellular Matrix using Purified Collagen, Elastin and Heparin: Vascular Scaffolding" (11:40)
David B. Masters, PhD, President, Gel-Del Technologies, Inc.

Session Abstract:

This session will feature speakers with diverse approaches to fabrication of cardiovascular/pulmonary tissue replacements, including synthetic polymer scaffolds, biopolymer scaffolds, and decellularized tissue scaffolds. 

Session Organizer Bio:

Robert T. Tranquillo, Professor and Department Head, Biomedical Engineering, University of Minnesota
Professor Tranquillo received his PhD in Chemical Engineering in 1986 from the University of Pennsylvania. He was a NATO Postdoctoral Fellow at the Center for Mathematical Biology at Oxford for one year before beginning his appointment in the Department of Chemical Engineering & Materials Science at the University of Minnesota in 1987. He has served as the head of the new Department of Biomedical Engineering since its inception in 2000. Professor Tranquillo has used a combined modeling and experimental approach to understand cell behavior, in particular, directed cell migration and cell-matrix mechanical interactions. More recently, his research program has focused on the role of cell behavior in cardiovascular and neural tissue engineering applications. His research has resulted in over 90 peer-reviewed publications. Professor Tranquillo is a Fellow of the American Institute of Medical and Biological Engineering and the Biomedical Engineering Society, and a Distinguished McKnight University Professor.

Speaker Bios:

Christopher K. Breuer, MD, Associate Professor of Surgery (Pediatrics) and of Pediatrics, Director of Tissue Engineering, Yale School of Medicine
Christopher Breuer, MD is an associate professor of surgery at the Yale School of Medicine where he directs the Yale Tissue Engineering Microsurgery Core. His research is both basic and applied. His work focuses on the development of an improved vascular graft specifically designed for use in congenital heart surgery where complications arising from the use of currently used synthetic vascular grafts are a leading cause of post operative morbidity and mortality.

Angela Panoskaltsis-Mortari, PhD, D (ABMLI), Pediatric BMT and Pulmonary Medicine
Originally trained in Immunology (UWO) and Pathology (UAB), Dr. Mortari is well-known for her work in lung injury and repair post-hematopoietic stem cell transplant. Her lab published the first decellularized whole lung bioreactor system and she is very proactive in converging the fields of pulmonary biology, bioengineering and stem cells. She has been a UMN faculty member (Pediatrics) since 1995.

David B. Masters, PhD, President, Gel-Del Technologies, Inc.
Dr. Masters is President and Founder of Gel-Del Technologies, Inc. His patented work includes clinically tested product development of a protein-based biomaterial that mimics the extracellular matrix for tissue repair/regeneration. He received Scholar Distinction and BA in Biochemistry/Biopsychology, MS in Chemistry, and PhD in Behavioral /Neural Sciences, Rutgers University. Dr. Masters attended Harvard Medical School as an Anesthesiology Research Fellow and studied implantable dosage forms with Dr. Robert Langer of MIT, resulting in publications, patents and licensed technology. Dr. Masters was promoted to Instructor in Anesthesiology at HMS and to Staff at Boston Children’s Hospital - Then, Assistant Professor/Associate Consultant Mayo Clinic (Rochester MN) and for three years was concurrent adjunct Assistant Professor in Pharmaceutics and Biomedical Engineering at University of Minnesota. Over the past decade his work at Gel-Del using protein matrices resulted in $7 million of NIH funding. Dr. Masters has over 60 peer-reviewed publications, book chapters and abstracts, and over 25 patents issued or pending.

Presentation Abstracts:

"Next Generation Tissue Engineered Vascular Grafts"
We performed the first clinical trial evaluating the use of tissue engineered vascular grafts in congenital heart surgery. Results of this trial demonstrated the feasibility and relative safety of using this technology in humans, however; it also revealed that the primary graft related complication was stenosis. In this presentation we will review recent results from our studies evaluating the cellular and molecular mechanisms underlying vascular neotissue formation and highlight how these studies are providing insights which we are using to direct the rational design of improved second generation tissue engineered vascular grafts which do not undergo stenosis.

"In Vivo Remodeling of a Completely Biological Vascular Graft"
A completely-biological graft that can be produced in just two months, possessing circumferential alignment/tensile anisotropy, that can be successfully implanted into the arterial system has not yet been reported. We recently demonstrated the ability to create such implantable arterial grafts using fibrin gel seeded with human dermal fibroblasts followed by conditioning in a pulsed-flow-stretch (PFS) bioreactor (Syedain et al. 2011). Here, we evaluated the in vivo performance of such grafts, specifically, decellularized engineered allografts in an interpositional sheep femoral artery model.  10/10 grafts were patent and fully recellularized, without evidence of aneurysm, sustained immune response, or mineralization and only minor neointima formation, for as long as 6 months implantation.

"Tissue Engineering Lungs from Bone Marrow"
Current progress will be shown in using decellularized whole lung matrix (DLM) from pigs set up in a bioreactor system to evaluate the potential of human multipotent stem (iPS) and other bone-marrow-derived cells. The ultimate goal is to provide an autologous source of transplantable lung tissue that would not be subject to immune-mediated rejection. 

"Biomimetic Extracellular Matrix using Purified Collagen, Elastin and Heparin: Vascular Scaffolding"
Our human-tested and patented Gel-Del® biomaterial mimics the body's tissue in composition and structure to allow integration, tissue repair, and regeneration. This medical material is manufactured in kilogram quantities with years of demonstrated lot consistency using quick-turnaround, scalable, disposable systems. The Gel-Del material is thermoplastic and easily fabricated into medical devices and coatings using FDA-clinical trial approved manufacturing, sterilization, packaging and 24 month stability. Our work includes vascular grafts with demonstrated regenerative tissue integration as small diameter femoral and iliac porcine artery replacements and as ovine A-V shunts (carotid to jugular), in NIH and DOD funded studies over the past 7 years.