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Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model

A great need exists for the development of a more representative in‐vitro model to efficiently screen novel thrombolytic therapies. We herein report the design, validation, and characterization of a highly reproducible, physiological scale, flowing clot lysis platform with real‐time fibrinolysis mon...

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Autores principales: Zeng, Ziqian, Christodoulides, Alexei, Alves, Nathan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189439/
https://www.ncbi.nlm.nih.gov/pubmed/37206217
http://dx.doi.org/10.1002/btm2.10511
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author Zeng, Ziqian
Christodoulides, Alexei
Alves, Nathan J.
author_facet Zeng, Ziqian
Christodoulides, Alexei
Alves, Nathan J.
author_sort Zeng, Ziqian
collection PubMed
description A great need exists for the development of a more representative in‐vitro model to efficiently screen novel thrombolytic therapies. We herein report the design, validation, and characterization of a highly reproducible, physiological scale, flowing clot lysis platform with real‐time fibrinolysis monitoring to screen thrombolytic drugs utilizing a fluorescein isothiocyanate (FITC)‐labeled clot analog. Using this Real‐Time Fluorometric Flowing Fibrinolysis assay (RT‐FluFF assay), a tPa‐dependent degree of thrombolysis was observed both via clot mass loss as well as fluorometrically monitored release of FITC‐labeled fibrin degradation products. Percent clot mass loss ranged from 33.6% to 85.9% with fluorescence release rates of 0.53 to 1.17 RFU/min in 40 and 1000 ng/mL tPa conditions, respectively. The platform is easily adapted to produce pulsatile flows. Hemodynamics of human main pulmonary artery were mimicked through matching dimensionless flow parameters calculated using clinical data. Increasing pressure amplitude range (4–40 mmHg) results in a 20% increase of fibrinolysis at 1000 ng/mL tPA. Increasing shear flow rate (205–913 s(−1)) significantly increases fibrinolysis and mechanical digestion. These findings suggest pulsatile level affects thrombolytic drug activities and the proposed in‐vitro clot model offers a versatile testing platform for thrombolytic drug screening.
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spelling pubmed-101894392023-05-18 Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model Zeng, Ziqian Christodoulides, Alexei Alves, Nathan J. Bioeng Transl Med Research Articles A great need exists for the development of a more representative in‐vitro model to efficiently screen novel thrombolytic therapies. We herein report the design, validation, and characterization of a highly reproducible, physiological scale, flowing clot lysis platform with real‐time fibrinolysis monitoring to screen thrombolytic drugs utilizing a fluorescein isothiocyanate (FITC)‐labeled clot analog. Using this Real‐Time Fluorometric Flowing Fibrinolysis assay (RT‐FluFF assay), a tPa‐dependent degree of thrombolysis was observed both via clot mass loss as well as fluorometrically monitored release of FITC‐labeled fibrin degradation products. Percent clot mass loss ranged from 33.6% to 85.9% with fluorescence release rates of 0.53 to 1.17 RFU/min in 40 and 1000 ng/mL tPa conditions, respectively. The platform is easily adapted to produce pulsatile flows. Hemodynamics of human main pulmonary artery were mimicked through matching dimensionless flow parameters calculated using clinical data. Increasing pressure amplitude range (4–40 mmHg) results in a 20% increase of fibrinolysis at 1000 ng/mL tPA. Increasing shear flow rate (205–913 s(−1)) significantly increases fibrinolysis and mechanical digestion. These findings suggest pulsatile level affects thrombolytic drug activities and the proposed in‐vitro clot model offers a versatile testing platform for thrombolytic drug screening. John Wiley & Sons, Inc. 2023-04-11 /pmc/articles/PMC10189439/ /pubmed/37206217 http://dx.doi.org/10.1002/btm2.10511 Text en © 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zeng, Ziqian
Christodoulides, Alexei
Alves, Nathan J.
Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
title Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
title_full Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
title_fullStr Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
title_full_unstemmed Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
title_short Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
title_sort real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189439/
https://www.ncbi.nlm.nih.gov/pubmed/37206217
http://dx.doi.org/10.1002/btm2.10511
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