The goal of this research plan is to translate the progress made with prior NIH funding into a completely biological tissue-engineered pulmonary valve replacement, made of tissue grown in vitro from fibroblast remodeled fibrin. This will be accomplished using (1) advances in heart valve bioreactor design and operation to strengthen the root segment and the root-leaflet attachment line, and (2) a new decellularization and optional recellularization strategy using mesenchymal stem cells to obviate the leaflet contraction that occurred post-implantation due to the transplanted fibroblasts, which are used to grow the tissue valve in vitro. This tissue-engineered heart valve (TEHV), both decellularized (relying on host cell invasion) and recellularized (with mesenchymal stem cells pre-implantation) will be validated in a lamb model to demonstrate growth capacity and sustained function of the engineered valve. Success will ultimately benefit approximately 10,000 pediatric patients in the U.S. annually and ultimately 100,000 patients in the U.S. annually if this TEHV can subsequently be improved to withstand forces associated with the aortic valve position. Enabling technologies relevant to other cardiovascular tissue engineering applications will be generated as a by-product of this research.

Public Health Relevance

In the United States alone, over 95,000 valve replacement surgeries are now performed annually according to the AHA. While mechanical and bioprosthetic heart valves have made a dramatic impact since their introduction in the 1960's, the 10-year mortality after replacement is still 30-55%. The need is particularly great for pediatric patients, since these valves do not have the capacity to grow. Thus, there is great interest in developing a new generation of tissue-engineered heart valves and this research is aimed at the design and testing of a completely biological living valve replacement.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lin, Sara
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University of Minnesota Twin Cities
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
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Reimer, Jay; Syedain, Zeeshan; Haynie, Bee et al. (2017) Implantation of a Tissue-Engineered Tubular Heart Valve in Growing Lambs. Ann Biomed Eng 45:439-451
Schmidt, Jillian B; Tranquillo, Robert T (2016) Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter Engineered Tissue Tubes. Ann Biomed Eng 44:1785-97
Syedain, Zeeshan; Reimer, Jay; Lahti, Matthew et al. (2016) Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs. Nat Commun 7:12951
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Syedain, Zeeshan; Reimer, Jay; Schmidt, Jillian et al. (2015) 6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep. Biomaterials 73:175-84
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