Extracellular matrix scaffold for cardiac repair

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-08, Vol.112 (9), p.I135-I143
• Main Authors: ROBINSON, Keith A, JINSHEN LI, MATHISON, Megumi, REDKAR, Alka, JIANHUA CUI, CHRONOS, Nicolas A. F, MATHENY, Robert G, BADYLAK, Stephen F
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Animals; Biocompatible Materials; Biological and medical sciences; Biomarkers; Blood and lymphatic vessels; Cardiology. Vascular system; Diseases of the aorta; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Extracellular Matrix - transplantation; Female; Flow Cytometry; Heart; Heart Failure - etiology; Heart Failure - surgery; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Ventricles - surgery; Male; Materials Testing; Medical sciences; Myocardial Infarction - complications; Myocardium - pathology; Polytetrafluoroethylene; Prostheses and Implants; Sus scrofa; Tissue Engineering; Urinary Bladder - ultrastructure; Wound Healing
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.104.525436

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. 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 alpha-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 alpha-sarcomeric actin-positive, intensely alpha-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. 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.