Bioactive surface coating for preventing mechanical heart valve thrombosis.


Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
09 2023
Historique:
received: 12 01 2023
revised: 13 04 2023
accepted: 04 05 2023
medline: 21 8 2023
pubmed: 18 5 2023
entrez: 17 5 2023
Statut: ppublish

Résumé

Prosthetic heart valves are the only treatment for most patients with severe valvular heart disease. Mechanical valves, made of metallic components, are the most long-lasting type of replacement valves. However, they are prone to thrombosis and require permanent anticoagulation and monitoring, which leads to higher risk of bleeding and impacts the patient's quality of life. To develop a bioactive coating for mechanical valves with the aim to prevent thrombosis and improve patient outcomes. We used a catechol-based approach to produce a drug-releasing multilayer coating adherent to mechanical valves. The hemodynamic performance of coated Open Pivot valves was verified in a heart model tester, and coating durability in the long term was assessed in a durability tester producing accelerated cardiac cycles. Coating antithrombotic activity was evaluated in vitro with human plasma or whole blood under static and flow conditions and in vivo after surgical valve implantation in a pig's thoracic aorta. We developed an antithrombotic coating consisting of ticagrelor- and minocycline-releasing cross-linked nanogels covalently linked to polyethylene glycol. We demonstrated the hydrodynamic performance, durability, and hemocompatibility of coated valves. The coating did not increase the contact phase activation of coagulation, and it prevented plasma protein adsorption, platelet adhesion, and thrombus formation. Implantation of coated valves in nonanticoagulated pigs for 1 month efficiently reduced valve thrombosis compared with noncoated valves. Our coating efficiently inhibited mechanical valve thrombosis, which might solve the issues of anticoagulant use in patients and the number of revision surgeries due to valve thrombosis despite anticoagulation.

Sections du résumé

BACKGROUND
Prosthetic heart valves are the only treatment for most patients with severe valvular heart disease. Mechanical valves, made of metallic components, are the most long-lasting type of replacement valves. However, they are prone to thrombosis and require permanent anticoagulation and monitoring, which leads to higher risk of bleeding and impacts the patient's quality of life.
OBJECTIVES
To develop a bioactive coating for mechanical valves with the aim to prevent thrombosis and improve patient outcomes.
METHODS
We used a catechol-based approach to produce a drug-releasing multilayer coating adherent to mechanical valves. The hemodynamic performance of coated Open Pivot valves was verified in a heart model tester, and coating durability in the long term was assessed in a durability tester producing accelerated cardiac cycles. Coating antithrombotic activity was evaluated in vitro with human plasma or whole blood under static and flow conditions and in vivo after surgical valve implantation in a pig's thoracic aorta.
RESULTS
We developed an antithrombotic coating consisting of ticagrelor- and minocycline-releasing cross-linked nanogels covalently linked to polyethylene glycol. We demonstrated the hydrodynamic performance, durability, and hemocompatibility of coated valves. The coating did not increase the contact phase activation of coagulation, and it prevented plasma protein adsorption, platelet adhesion, and thrombus formation. Implantation of coated valves in nonanticoagulated pigs for 1 month efficiently reduced valve thrombosis compared with noncoated valves.
CONCLUSION
Our coating efficiently inhibited mechanical valve thrombosis, which might solve the issues of anticoagulant use in patients and the number of revision surgeries due to valve thrombosis despite anticoagulation.

Identifiants

pubmed: 37196847
pii: S1538-7836(23)00416-6
doi: 10.1016/j.jtha.2023.05.004
pii:
doi:

Substances chimiques

Fibrinolytic Agents 0
Anticoagulants 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2485-2498

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interests C.O., P.L., C.D., and C.J. are inventors on a patent owned by the University of Liège related to medical devices coated with the presented technology (WO2018122318A1).

Auteurs

Patrizio Lancellotti (P)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.

Abdelhafid Aqil (A)

Center for Education and Research on Macromolecules, CESAM Research Unit, University of Liège, Liège, Belgium.

Lucia Musumeci (L)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.

Nicolas Jacques (N)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.

Bartosz Ditkowski (B)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.

Margaux Debuisson (M)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.

Marc Thiry (M)

Laboratory of Cellular and Tissular Biology, GIGA-Neurosciences, Cell Biology, University of Liège, Liège, Belgium.

Julien Dupont (J)

Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.

Alexandra Gougnard (A)

Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.

Charlotte Sandersen (C)

Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.

Jean-Paul Cheramy-Bien (JP)

Department of Cardiovascular and Thoracic Surgery, Centre Hospitalier Universitaire of Liège, University of Liège, Liège, Belgium; Surgical Research Center, GIGA-Cardiovascular Science Unit, University of Liège, Liège, Belgium.

Natzi Sakalihasan (N)

Department of Cardiovascular and Thoracic Surgery, Centre Hospitalier Universitaire of Liège, University of Liège, Liège, Belgium; Surgical Research Center, GIGA-Cardiovascular Science Unit, University of Liège, Liège, Belgium.

Alain Nchimi (A)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.

Christophe Detrembleur (C)

Center for Education and Research on Macromolecules, CESAM Research Unit, University of Liège, Liège, Belgium.

Christine Jérôme (C)

Center for Education and Research on Macromolecules, CESAM Research Unit, University of Liège, Liège, Belgium.

Cécile Oury (C)

Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium. Electronic address: cecile.oury@uliege.be.

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Classifications MeSH