Real-time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in-vitro thrombolysis model.
drug delivery
fibrinolysis
in‐vitro model
physiological model
shear flow
thrombolysis
Journal
Bioengineering & translational medicine
ISSN: 2380-6761
Titre abrégé: Bioeng Transl Med
Pays: United States
ID NLM: 101689146
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
06
09
2022
revised:
06
01
2023
accepted:
08
03
2023
medline:
19
5
2023
pubmed:
19
5
2023
entrez:
19
5
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 37206217
doi: 10.1002/btm2.10511
pii: BTM210511
pmc: PMC10189439
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e10511Informations de copyright
© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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