The goal of this project is to create a heart valve that can grow with children and never require replacement. Using a biologically-engineered collagenous matrix in the form of a tube that has been shown to grow as a pulmonary artery replacement in lambs, and a novel design for a heart valve made from these tubes and degradable suture that confers durable commissures as well as valve growth potential, we will design, optimize, test, and implant tri-tube valves in a juvenile sheep model to demonstrate valve growth.
Aim 1 will use computer-aided design (a fluid-structure interaction model for valve opening and finite element model for the closed valve state) to screen combinations of design parameters (defining coaptation area and geometry) for efficient valve function, Aim 2 will test the optimal designs in a pulse duplicator and validate/refine the CAD models, and Aim 3 will involve studies of the valve in growing juvenile sheep. Long-term studies of pulmonary and aortic valve replacement are designed with measurements to rigorously address valve growth.

Public Health Relevance

Unlike the assortment of efficacious heart valves available to clinicians for adult patients, a heart valve that can grow for pediatric patients has not yet been demonstrated. Several thousand children born each year with congenital heart valve defects thus face the grim prospect of repeated open heart surgery until adulthood in order to upsize the inert valves they outgrow. The goal of this project is to create a heart valve that can grow with children and never requires replacement using a material grown from skin cells that can grow.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL107572-08
Application #
9935967
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Natarajan, Aruna R
Project Start
2011-04-01
Project End
2022-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
8
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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
Schmidt, Jillian B; Chen, Kelley; Tranquillo, Robert T (2016) Effects of Intermittent and Incremental Cyclic Stretch on ERK Signaling and Collagen Production in Engineered Tissue. Cell Mol Bioeng 9:55-64
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
Reimer, Jay M; Syedain, Zeeshan H; Haynie, Bee H T et al. (2015) Pediatric tubular pulmonary heart valve from decellularized engineered tissue tubes. Biomaterials 62:88-94
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Syedain, Zeeshan H; Meier, Lee A; Reimer, Jay M et al. (2013) Tubular heart valves from decellularized engineered tissue. Ann Biomed Eng 41:2645-54
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