Abstract 16829: Pericardium Improves Cardiac Scaffold Mechanics and Cell Retention

Abstract

Background: Building a transplantable bioartificial heart from a decellularized extracellular matrix (dECM) scaffold is a promising option to solve the donor organ shortage. Yet, strategies are needed for cell retention, survival and function in recellularized dECM hearts. The objective of this work was to determine if the preservation of the pericardium during decellularization provides benefit to the resulting dECM mechanically and functionally when recellularized. Methods: Hearts ± pericardium (8.0 ± 1.3 g) from New Zealand White rabbits (2.9 ± 0.6 kg) were perfusion decellularized via Langendorff under constant pressure (60 mmHg). Perfusion solutions were: hypertonic NaCl (500mM), hypotonic NaCl (20mM), 1% sodium dodecyl sulfate (SDS), peracetic acid (0.01%) in 1% SDS, and PBS. After decellularization, dECM hearts (n=7 with pericardium, n=9 without pericardium) were sectioned into 2 mm thick rings. Force-elongation curves, DNA, SDS, glycosaminoglycan (GAG) content, and matrix fiber density were measured. Vasculature of dECM whole hearts (n=14) was recellularized by anterograde infusion of human endothelial cells (hECs, 86.09 ± 18.26 million) through the coronary vasculature (2 ml/min at 1.5 million cells/ml). Results: Hearts decellularized with pericardium contained more DNA (427± 26, n=6, vs. 217 ± 46 ng/mg, n=7, p<0.05) than those without, but remnant DNA content was less than 10% of cadaveric. The GAG content was comparable in hearts with or without pericardium. Matrix fiber densities were higher in hearts with pericardium (64.47% ± 1.55%, vs. 54.28% ± 2.45%, p<0.01, n=3). Force-elongation tests showed that rings of left ventricle with pericardium had better flexibility with a slope of 1.56% ± 0.65% mm/gram vs. 0.91% ± 0.28% mm/gram (p<0.01, n=3 hearts per group). In recellularized hearts, more hECs were retained (83.82% vs. 70.04%, p<0.05, n=7) in hearts with pericardium. Conclusion: Retaining the native pericardium preserves the mechanical flexibility and matrix fiber densities of dECM scaffold, which promotes cell retention during recellularization.