A significant number of congenital cardiac malformations include either stenosis or atresia of the pulmonary valve with most able to be corrected early in life. The homograft, prosthetic, or bioprosthetic options available to serve as a pulmonary valve lack growth potential and are susceptible to infection, thrombosis, or calcification. They also commit the children to multiple operations. Tissue engineering using living cells seeded on scaffolds in vitro offers the potential to create a living valve structure, which could overcome the shortcomings of currant devices. Significant progress has been made toward realization of this goal with tissue-engineered valves having been implanted and functioning in animals for up to 6 months. In order to continue progressing toward a clinically applicable TE pulmonary valve, fundamental questions regarding the types of cells to be used to seed the polymer scaffold, the optimal in vitro physical signaling conditions, and the optimal biomechanical characteristics of the polymer scaffold remain to be answered. The studies proposed will address if cells obtained relatively non-invasively from blood and/or bone marrow will be suitable for TE valves, the influence of biomechanical properties of the scaffold in the development of TE valves in vitro, and the effects of shear stress and hydrostatic pressure signals on the in vitro development of TE valves. The final studies will address the relationship between the characteristics of the TE valve at the time of implantation and the long-term function of these valves. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EB003353-01
Application #
6737856
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Temple-Oconnor, Meredith D
Project Start
2003-09-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$48,148
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Sales, Virna L; Mettler, Bret A; Engelmayr Jr, George C et al. (2010) Endothelial progenitor cells as a sole source for ex vivo seeding of tissue-engineered heart valves. Tissue Eng Part A 16:257-67
Mettler, Bret A; Sales, Virna L; Stucken, Chaz L et al. (2008) Stem cell-derived, tissue-engineered pulmonary artery augmentation patches in vivo. Ann Thorac Surg 86:132-40;discussion 140-1
Sales, Virna L; Mettler, Bret A; Lopez-Ilasaca, Marco et al. (2007) Endothelial progenitor and mesenchymal stem cell-derived cells persist in tissue-engineered patch in vivo: application of green and red fluorescent protein-expressing retroviral vector. Tissue Eng 13:525-35
Sales, Virna L; Engelmayr Jr, George C; Mettler, Bret A et al. (2006) Transforming growth factor-beta1 modulates extracellular matrix production, proliferation, and apoptosis of endothelial progenitor cells in tissue-engineering scaffolds. Circulation 114:I193-9
Breuer, Christopher K; Mettler, Bret A; Anthony, Tiffany et al. (2004) Application of tissue-engineering principles toward the development of a semilunar heart valve substitute. Tissue Eng 10:1725-36