Extracellular Matrix Scaffold for Cardiac Repair

Abstract

Background— Heart failure remains a significant problem. Tissue-engineered cardiac patches offer potential to treat severe heart failure. We studied an extracellular matrix scaffold for repairing the infarcted left ventricle. Methods and Results— Pigs (n=42) underwent left ventricular (LV) infarction. At 6 to 8 weeks, either 4-layer multilaminate urinary bladder-derived extracellular matrix or expanded polytetrafluoroethlyene (ePTFE) was implanted as full-thickness LV wall patch replacement. At 1-week, 1-month, or 3-month intervals, pigs were terminated. After macroscopic examination, samples of tissue were prepared for histology, immunocytochemistry, and analysis of cell proportions by flow cytometry. One-week and 1-month patches were intact with thrombus and inflammation; at 1 month, there was also tissue with spindle-shaped cells in proteoglycan-rich and collagenous matrix. More α-smooth muscle actin-positive cells were present in urinary bladder matrix (UBM) than in ePTFE (22.2±3.3% versus 8.4±2.7%; P =0.04). At 3 months, UBM was bioresorbed, and a collagen-rich vascularized tissue with numerous myofibroblasts was present. Isolated regions of α-sarcomeric actin-positive, intensely α-smooth muscle actin-immunopositive, and striated cells were observed. ePTFE at 3 months had foreign-body response with necrosis and calcification. Flow cytometry showed similarities of cells from UBM to normal myocardium, whereas ePTFE had limited cardiomyocyte markers. Conclusions— Appearance of a fibrocellular tissue that included contractile cells accompanied biodegradation of UBM when implanted as an LV-free wall infarction patch. UBM appears superior to synthetic material for cardiac patching and trends toward myocardial replacement at 3 months.