This Phase I proposal seeks support to evaluate the feasibility of developing an extracellular matrix (ECM) biologic scaffold as a repair device for atrial septal defects (ASD). ASDs are one of the most common forms of congenital heart disease and account for approximately 30-40% of all congenital heart defects seen in adults. Closure of an ASD can be performed either surgically or percutaneously, and the success rate of this procedure is very high. However, recent reports suggest that complications with severe hemodynamic consequences do occur and are a result of the metal cage configuration of the repair device. This cage configuration serves as an abrasive surface to adjacent atrial roof and aortic tissues. The proposed studies would utilize non-abrasive, naturally occurring ECM configured in mechanically-appropriate, multilaminate form as the repair device. This Phase I proposal has three Specific Aims. The first Specific Aim would develop a prototype ECM device suitable for percutaneous delivery. The second Specific Aim would evaluate the biomechanical and biophysical properties of the device. The final Specific Aim would determine functionality in a pig model of surgically created ASD. These studies will be conducted by an experienced team of investigators at ACell, Inc., with a subcontract for the animal studies at the Center for Preclinical Studies within the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Clearly defined criteria for success are identified for each Specific Aim and a timeline for completion of the studies is provided. ? ?
