Time Related Histopathologic Changes of Acellularized Xenogenic Pulmonary Valved Conduits

Abstract

A biologically engineered xenogenic heart valve based on the concept of acellularization offers promise as a means of overcoming the limitations of current prosthetic valves. We evaluated the process of repopulation by recipient cells on an acellularized xenograft treated with a saline (NaCl)-sodium dodecyl sulfate (SDS) solution. Porcine pulmonary valved conduits acellularized with NaCl-SDS solution were implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were sacrificed at 1 week and at 1, 3, 6, and 12 months after implantation. Echocardiographic evaluations of the valves were performed before sacrifice. Visual inspections and histopathologic examinations of the explanted xenogenic valved conduits were performed. Immunohistochemical staining was used to identify the composition of the recellularized cells. Fibroblasts and myofibroblasts were stained by vimentin and smooth muscle actin, and endothelial cells were stained by factor VII related antigen and CD31. Echocardiographic examinations of implanted acellularized xenogenic pulmonary valves revealed satisfactory function except for mild regurgitation and stenosis. On gross examination, all leaflets were well preserved, and no calcification was observed. Microscopic analysis of the acellularized leaflets showed progressive cellular ingrowth over time. The recellularization started from the leaflet base and progressed toward the free margin. Microthrombi were detected on unrecellularized portions. Inflammatory response was detected in the early phase, although it gradually subsided. At 6 months after implantation, cellular ingrowth by fibroblasts, myofibroblasts, and endothelial cells progressed up to 50% of the leaflet's height and progressively increased to 70% after 12 months. Extracellular matrices were regenerated by repopulating cells on the recellularized portion. This study suggests that acellularized xenogenic porcine valved conduits are biocompatible heart valve prostheses that are repopulated with autologous cells and extracellular matrices over a reasonable span of time and preserve the functional integrity without degeneration or calcification of leaflets.