In Vivo Remodeling of an Extracellular Matrix Cardiac Patch in an Ovine Model

摘要

Lack of an ideal patch material for cardiac repairs continues to challenge congenital heart surgeons. The current materials are unable to grow and result in scarring, contraction, and arrhythmias. An acellular extracellular matrix (ECM) patch derived from porcine small intestinal submucosa has demonstrated remodeling potential when used to repair various tissues. This study investigated the in vivo electrophysiologic, mechanical, and histological properties of an ECM patch used to repair a right-ventricular (RV) wall defect in a growing ovine model. A full-thickness, 2 x 2 cm RV defect was created in 11 juvenile sheep and repaired with an ECM patch. Longitudinal RV three-dimensional-electrical mapping, magnetic resonance imaging (MRI), and histological analysis were performed at 3, 6, 9, and 12 months. Three-dimensional mapping demonstrated consistent conduction across the patch with little to no difference in voltage, but conduction velocity was consistently less than native myocardium. Magnetic resonance imaging revealed changing strain properties of the patch which by 9-12 months resembled native tissue. Histologic analysis at 3 months demonstrates cardiomyocyte degeneration and partial replacement via proliferation of connective tissue cells that were predominately fibroblasts and smooth muscle cells. There was marked neovascularization and an absence of calcification at 12 months. Over time, the ECM patch remained viable with stable muscle at the edges. In growing sheep, an ECM patch becomes a viable tissue and remains so up to at least a year. Although ECM demonstrates some functional aspects of remodeling to native myocardium, histologically it remained immature.