A Fibrin-Thrombin Based In Vitro Perfusion System to Study Flow-Related Prosthetic Heart Valves Thrombosis

Yevgeniy Kreinin, Yahel Talmon, Moran Levi, Maria Khoury, Itay Or, Mahli Raad, Gil Bolotin, Josué Sznitman, Netanel Korin

Research output: Contribution to journalArticlepeer-review


Prosthetic heart valve (PHV) replacement has increased the survival rate and quality of life for heart valve-diseased patients. However, PHV thrombosis remains a critical problem associated with these procedures. To better understand the PHV flow-related thrombosis problem, appropriate experimental models need to be developed. In this study, we present an in vitro fibrin clot model that mimics clot accumulation in PHVs under relevant hydrodynamic conditions while allowing real-time imaging. We created 3D-printed mechanical aortic valve models that were inserted into a transparent glass aorta model and connected to a system that simulates human aortic flow pulse and pressures. Thrombin was gradually injected into a circulating fibrinogen solution to induce fibrin clot formation, and clot accumulation was quantified via image analysis. The results of valves positioned in a normal versus a tilted configuration showed that clot accumulation correlated with the local flow features and was mainly present in areas of low shear and high residence time, where recirculating flows are dominant, as supported by computational fluid dynamic simulations. Overall, our work suggests that the developed method may provide data on flow-related clot accumulation in PHVs and may contribute to exploring new approaches and valve designs to reduce valve thrombosis.

Original languageEnglish
Pages (from-to)1665-1677
Number of pages13
JournalAnnals of Biomedical Engineering
Issue number6
StatePublished - 8 Mar 2024


  • Fibrin clot
  • Hemodynamics
  • Prosthetic heart valve
  • Recirculating flow
  • Thrombosis
  • Models, Cardiovascular
  • Perfusion
  • Heart Valve Prosthesis
  • Humans
  • Thrombin
  • Aortic Valve/surgery
  • Fibrin/metabolism

ASJC Scopus subject areas

  • Biomedical Engineering


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