Abstract 3721: Tissue-engineered Extracellular Matrix Scaffold as a Left Ventricular Cardiac Surgical Patch: Long-Term Results in a Porcine Model of Myocardial Infarction
Heart failure is a growing healthcare problem. Tissue-engineered cardiac patches offer potential to treat severe heart failure. Interim results using extracellular matrix (ECM) biological scaffold material in the infarcted left ventricle (LV) were previously reported.
Methods & Results Pigs (n=16) underwent LV infarction by coronary embolization. At 6 – 8 weeks either 4-ply multilaminate urinary bladder-derived ECM (UBM) or ePTFE was implanted as full-thickness LV free wall patch replacement. Animals were terminated at 3- and 6-mo intervals; 6-mo pigs underwent LV functional study. At 3-mo UBM was bioresorbed and a collagen-rich vascularized tissue with fibroblasts and myofibroblasts was present. Isolated regions of α-sarcomeric actin-positive, intensely α-SM actin-positive, and striated cells were seen. By flow cytometry α-SM actin-positive cell population of UBM was higher than ePTFE (26±5% vs. 10±3%, P=0.04) and PCNA+ cells tended to be higher (37±7% vs. 26±2%, P=0.10).Tropomyosin- and connexin43-positive cell proportions were similar between normal myocardium and UBM, with few such cells present in ePTFE. Samples double-stained for α-SM and sarcomeric actin showed cells co-expressing the two filaments in both groups, whereas only UBM had cells uniquely expressing sarcomeric actin. ePTFE at 3-mo had foreign-body response with fibrotic encapsulation, abscess, necrosis, and calcification. At 6-mo a mixed response was seen in UBM-implanted pigs. The tissue in patched regions included cardiac muscle islands as well as blood vessels, fibrosis, and adipocytes. Ventricles of UBM-implanted 6-mo pigs were dilated compared to ePTFE and had increased diastolic compliance.
Conclusions Appearance of a fibrocellular tissue that included contractile cells accompanied biodegradation of UBM when implanted as an LV free wall replacement patch. Multilaminate UBM scaffold is suitable for cardiac patching and trends towards myocardial replacement as early as 3 mo; longer-duration implants in this configuration favor ventricular dilation and diastolic dysfunction. Ongoing studies address methods for improving cardiac patching with ECM, additional cardiac applications, and mechanisms of cell recruitment and tissue remodeling.