The ability to create robust, fault-tolerant hardware for critical systems is necessary for the advancement of NASA's manned space program. Naturally engineered organisms have repeatedly solved this problem by evolving a multitude of biological systems over billions of years. The vertebrate cardiovascular system is one such example of nature's ability to grow highly robust hardware essential for organismal survival. The modern vertebrate circulatory system is composed of a biological pump and associated vessels whose operation depends on a myriad of factors including delicate flow-structure interactions, turbulence and mixing, chemical balances, cellular transduction and a sophisticated feedback system based on advanced sensing and actuation components. Conventional engineering and biomimetic approaches offer little prospect of being able to duplicate such a system due to our inability to reproduce both the small, multifunctional, self-repairing components and the complex, redundant control systems found in naturally engineered organisms. An alternative solution, offered by biosynthetic engineering, is to use natural design principles to grow the hardware artificially. We are now taking the first steps in this direction by uncovering the design principles used by nature to develop the most famous biological pump, the heart. The formation of a functional heart is regulated by the coordinated interplay between a genetic program, fluid mechanical stimuli, and the inter and intra-cellular processes that link them. We have developed a suite of interrogative tools that are allowing an unprecedented glimpse into the workings of the developing heart. Quantitative descriptions of flow-induced forces and the response of living vascular endothelial cells, including transduction pathways and resulting gene expression are being described in vivo. Our ability to modify the genetic structure of model organisms and influence that developmental blueprint through epigenetic means will allow us to greatly enhance the efforts being made in modern cardiovascular tissue engineering. We intend to invite a distinguished panel of experts to a workshop in the spring of 2004 to map out the next steps in this research path.