Chronic myocardial infarction (CMI) is the leading cause of death and disability in the U.S. with an estimated 16.3 million individuals suffering from this condition which was responsible for 1 in 6 deaths in the United States in 2007. Current medical and surgical treatments aim to retard the formation of negative tissue remodeling but fail to restore cardiac function. Cell based regenerative therapy for CMI has shown promise but has achieved limited success in the clinic due to poor donor cell retention and survival, and limited interaction with the diseased tissue. The goal of this study will be to design and evaluate a multi-modal device that combines a commercially available, FDA approved, extracellular matrix scaffold (SIS-ECM marketed as CorMatrix) seeded with bone marrow-derived mesenchymal stem cells (MSC's.) We will be optimizing a clinically relevant porcine CMI model to show analogy for humans, and develop the proposed device using either human or porcine MSC's which will include rigorous in vitro and in vivo safety testing for the design candidate (DC). The optimized porcine MSC seeded device will then be implanted into the porcine CMI model for safety and efficacy testing. Primary success for this study will be to show a significant improvement in left ventricle ejection fraction that translates into a clinically relevant improvement in cardiac function. Other success criteria includes tissue neo-formation and beneficial remodeling. The proposed device is expected to improve structural integrity, increase localized delivery of effector cells, and provide guidance cues for a beneficial myocardial remodeling. This project will support a future phase 1 clinical trial using the target device, using ECM seeded with human MSC's for patients suffering from CMI.