Cardiovascular Developmental Bioengineering Lab

Research

Mechanical Regulation of Embryonic Valvulogenesis

Valvulogenesis is the process by with the valves of the heart originate and morph into mature thin fibrous leaflets. These primitive valves must insure unidirectional blood flow through the heart as it grows. We recently discovered that the formation of valve tissue is directly related to the changes in mechanical environment. At the same time, the nascent cells transform into mature valvular fibroblasts and endothelial cells. The majority of this process is completely unknown, yet if uncovered, this knowledge may form the basis for many novel valvular engineering stratgies.

Our research efforts in this thrust seek to identify the mechanisms by which mechanical forces (blood pressure, tissue strain, wall shear stress, etc.) signal changes in developing valves at the cell and tissue level. We tackle this through animal model study, in vitro experimentation, and computational modeling. Our lab has developed special techniques and imaging technologies to quantify and alter the local mechanical environment of developing embryos. We combine tissue engineering with bioMEMS technologies to create well controlled, high throughput in vitro analogs of key aspects of embryonic valve development that we can use to ascertain the mechanisms behind these phenomena. The data that we obtain can then be used to refine computational models to predict the effects of other permutations. The ultimate goal is to discover next generation technologies that are developmentally inspired. Applications include creating more reliable animal models of heart defects, developing imaging techniques to enable earlier and more quantitative diagnosis of embryonic defects, designing devices to enable fetal intervention to rescue cardiac defects before they progress to life threatening situations.

Related Publications:
- [PDF] Unique Morphology and Focal Adhesion Development of Valvular Endothelial Cells in Static and Fluid Flow Environments (external link), Jonathan T. Butcher, Andrea M. Penrod, Andres J. Garcia, and Robert M. Nerem from Arteriosclerosis, Thrombosis, and Vascular Biology (2004)

- [PDF] Valvular Endothelial Cells Regulate the Phenotype of Interstitial Cells in Co-Culture: Effects of Steady Shear Stress (external link), Jonathan T. Butcher and Robert M. Nerem from Tissue Engineering (2006)

- [PDF] Transcriptional Profiles of Valvular and Vascular Endothelial Cells Reveals Phenotypic Differences: Influence of Shear Stress (external link), Jonathan T. Butcher, Sarah Tressel, Tiffany Johnson, Debi Turner, George Sorescu, Hanjoong Jo, Robert Nerem from Arteriosclerosis, Thrombosis, and Vascular Biology (2006)

- Mechanobiology of the Aortic Valve, Jonathan T. Butcher, Craig A. Simmons, and James N. Warnock from Journal of Heart Valve Disease (2008)

- Cyclic Strain Regulates Pro-Inflammatory Protein Expression in Porcine Aortic Valve Endothelial Cells, Scott A. Metzler, CA Pregonero, Jonathan T. Butcher, SC Burgess, and James N. Warnock from Journal of Heart Valve Disease (2008)