A New Hemodynamic Ex Vivo Model for Medical Devices Assessment
Résumé
Introduction: In stent restenosis (ISR) remains a major public health concern with an increased
morbidity, mortality and health-related costs. Drug-eluting stents (DES) have reduced ISR, but
are associated with healing-related issues or hypersensitivity reactions, leading to an increased
risk of late acute stent thrombosis. Evaluations of new DES are based on animal models or in
vitro release systems which show several limitations. The role of flow and shear stress on
endothelial cell and ISR has also been emphasized. The aim of this work was to design and first
evaluate an original bioreactor, reproducing ex vivo hemodynamic and biological conditions
similar to human conditions, to further evaluate new DES.
Methods & Results: This bioreactor was designed to study up to 6 stented arteries connected in
bypass, immersed in a culture box, in which circulated a physiological systolo-diastolic resistive
flow. Two centrifugal pumps drove the flow. The principal pump generated pulsating flows by
modulation of rotation velocity, and the second pump worked at constant rotation velocity,
ensuring the counter pressure levels and backflows. The flow rate, the velocity profile, the arterial
pressure and the resistance of the flow were adjustable. The bioreactor was placed in an incubator
to reproduce a biological environment. A first experience of feasibility was realized over a period
of 24 days. Three rat aortic thoracic arteries were placed into the bioreactor, immersed in cell
culture medium change every 3 days, and with a circulating systole diastolic flux circulating
among the entire experimentation. There was no infection, no leak. At the end of
experimentation, a morphometric analysis was performed confirming the viability of the arteries.
Conclusion: We design and patent an original hemodynamic ex vivo model to further study new
DES and ISR. We will next validate this ex vivo model of ISR reproducing this experimentation
with stented arteries. Once validated, this bioreactor will allow characterization of the velocity
field and drug transfers within a stented artery with new functionalized DES, with experimental
means not available in vivo. Another main point will be the reduction of animal experimentation,
and the availability of first results of new DES in human tissues (human infra popliteal or
coronary arteries collected during human donation).
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