Hemocompatibility of Bioprosthetic valve in bovine pericardium is based on fibrin formation and its endothelization

Introduction Bioprosthetic heart valves (BV) made of xenogenic pericardium fixed with glutaraldehyde have been developed more than 30 years ago. The concept of cross linking collagenous fibers to ensure in-vivo stability of the scaffold and reducing antigenic immune response by fixation resulted in successful clinical evaluations and a lower risk of thromboembolism thus eliminating the need for a lifelong anticoagulation. To explain these clinical results, an acquired hemocompatibility process has been proposed but never extensively studied because of the impossibility to access not degenerated material. Objective To study and understand mechanisms of acquired hemocompatibility, we explored non degenerated BV from 9 different patients implanted with a Carmat total artificial heart (C-TAH) and four BV duration from 45 to 270 days. Method We performed classic histopathology and immunophenotypic characterization of explanted BV. Biological deposit has been also explored by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Result In short implantation duration time, we observed a fibrin deposit with inflammatory cells and pseudotubes formation. Histological sections showed superficial infiltration of cells, persisting in long duration but not damaging integrity of the pericardium. The fibrin deposit is then organized in a compacted smooth fibrin network in longer implantation durations. Endothelial cells (EC) monolayer covering has also been observed on this fibrin cap, the percentage of the BV surface with EC covering increasing along months. This endothelial cells covering is positive for VE-Cadherin, with flat nucleus and tight junctions. Conclusion Healthy BV implanted with C-TAH enabled us to study, for the first time, non-degenerated implanted valve in human. Biomaterial passivation by an organized fibrin deposit and formation of EC monolayer on top achieve an optimal hemocompatibility without any modification of pericardial tissue.