Progressive endothelial coverage enhances hemocompatibility and prevents calcification in bioprosthetic valve tissue
Poitier B. Richez U. Roux-de-Bezieux J. Ivak P. Rancic J. Charrier H. Latremouille C. Peronino C. Roussel J.C. Rossi E. El-Batti S. Kindo M. Saubamea B. Pya Y. Lesaffre C. Capel A. Achouh P. Netuka I. Smadja D.M.
May 2026Springer Science and Business Media B.V.
Angiogenesis
2026#29Issue 2
Background: Exploring the hemocompatibility of bioprosthetic heart valves (BHVs) has been challenging due to the scarcity of non-degenerated material. Objectives: This study has two complementary objectives (1) To characterize the extent and temporal kinetics of endothelial coverage of BHVs implanted in humans; (2) To investigate, in a rat model, the impact of pericardial endothelialization on tissue calcification. Methods: We employed histology and electron microscopy to assess cellular organization in non-degenerated BHVs and conducted hemodynamic simulations to evaluate shear stress fields in the ejection valves area. Furthermore, we investigated the impact of pericardium endothelial coverage on calcification using endothelial colony-forming cells (ECFCs) cultured on bovine pericardium discs implanted in athymic nude rats for 18 days. Calcium content was quantified through acetylene flame atomic absorption spectrophotometry. Results: We observed inflammatory cell infiltration within all explanted BHVs, as well as fibrin deposit on top of the leaflets. Endothelial coverage emerged in long-term implants (> 180 days) but remained incomplete in aortic valves, which could be linked to high shear stress levels in aortic position confirmed in hemodynamic simulations. Besides, the rat experiments revealed that the discs covered with fibrin + ECFCs were significantly less calcified than those covered with fibrin alone (respectively, median = 0.9 µg Ca/mg tissue; IQR: 0.7–1.1 vs median = 18.3 µg Ca/mg tissue; IQR: 9–34.9; p = 0.0003), and less extensively colonized by neutrophils. Conclusions: Human explanted BHVs showed intact leaflets with a fibrin layer and organized endothelial coverage, without detectable calcification over the short observation period. In rats, endothelialization was associated with significantly reduced pericardial calcification, suggesting a potential protective effect. However, the limited follow-up in humans precludes conclusions on a causal role of endothelial coverage in hemocompatibility or protection against calcification.
Biomaterials , Bioprosthetic heart valve , Bioprosthetic total artificial heart , Bovine pericardium , Calcification , Endothelial cells , Hemocompatibility
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INSERM PARCC Georges Pompidou European Hospital, Université Paris Cité, 56 Rue Leblanc, Paris, 75015, France
Cardiovascular Surgery Department, AP-HP, Georges Pompidou European Hospital, Paris, 75015, France
Carmat SA, Vélizy-Villacoublay, France
Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Department of Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
Thoracic and Cardiovascular Surgery Department, Thorax Institute, University Hospital of Nantes, Nantes, France
INSERM, Optimisation Thérapeutique en Neuropharmacologie OTEN U1144, Université Paris-Cité, Paris, 75006, France
Cardiovascular Surgery Department, University Hospital of Strasbourg, Strasbourg, France
Plateforme d’Imagerie Cellulaire et Moléculaire (PICMO), US25 INSERM, UAR3612 CNRS, Faculté de Pharmacie de Paris, Université Paris Cité, Paris, France
National Research Cardiac Surgery Center, Astana, Kazakhstan
Hematology Department, AP-HP, Georges Pompidou European Hospital, Paris, 75015, France
INSERM PARCC Georges Pompidou European Hospital
Cardiovascular Surgery Department
Carmat SA
Department of Cardiovascular Surgery
Department of Physiology
Thoracic and Cardiovascular Surgery Department
INSERM
Cardiovascular Surgery Department
Plateforme d’Imagerie Cellulaire et Moléculaire (PICMO)
National Research Cardiac Surgery Center
Hematology Department
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