Cardiovascular disease is the leading cause of morbidity and mortality in developed countries and is the number one cause of death in the United States. Current treatments include drug therapy, gene therapy, surgical interventions, heart transplants, and tissue engineering. The goal of this dissertation was to combine the sciences of genetic and tissue engineering to create a three dimensional (3D) engineered construct with cardiomyocytes derived from genetically selected embryonic stem (ES) cells that could be used as an in vitro model to study the effects of mechanical and electrical stimulation on the differentiation of ES cells. To investigate this, two custom devices were built to deliver precise, reproducible, and long-term mechanical and electrical stimulation regiments to the constructs To optimize construct constituents and test the efficacy of these devices. 3D scaffolds containing HL-1 cells were studied. These experiments showed that an optimal ratio of cells and ECM proteins (0.2 mg collagen, 0.01 mg fibronectin, and 6 x 106 cells) was necessary to create constructs with the structural integrity necessary for use in the devices. Also, the mechanical loading device was shown to be efficacious by encouraging cellular alignment with distinct sarcomeric structures, development of dense cell boundary layers and homogeneous cell distributions throughout the construct's central regions Parallel experiments using constructs containing ES cells revealed that 0.4 mg collagen, 0.01 mg fibronectin and 6 x 106 cells were optimal. These experiments led to the discovery of a synergistic relationship between mechanical and electrical stimulation. A sequential regiment of electrical stimulation, followed by mechanical loading, resulted in the most significant switch from the expression of fetal genes (alpha-skeletal actin and beta-MHC) to adult cardiac genes (alpha-cardiac actin and alpha-MHC). Also, these constructs contained myofiber like structures, organized sarcomeric structures and distinct gap junctions similar to those found in the native neonatal heart This dissertation takes steps toward the development of a 3D model of the developing heart using a renewable cell source embedded in a defined ECM scaffold and exposed to mechanical and electrical stimuli, and provides the experimental foundation for those developing alternative treatments for those suffering from heart disease