科研之友
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摘要
Background: In-stent restenosis (ISR) remains a major public health concern associated with an increased morbidity, mortality, and health-related costs. Drug-eluting stents (DES) have reduced ISR, but generate healing-related issues or hypersensitivity reactions, leading to an increased risk of late acute stent thrombosis. Assessments of new DES are based on animal models or in vitro release systems, which have 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, replicating ex vivo hemodynamic and biological conditions similar to human conditions, to further evaluate new DES. Methods: 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 main 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. Results: A first feasibility experience was performed over a 24-day period. Three rat aortic thoracic arteries were placed into the bioreactor, immersed in cell culture medium changed every 3 days, and with a circulating systolic and diastolic flux during the entire experimentation. There was no infection and no leak. At the end of the experimentation, a morphometric analysis was performed confirming the viability of the arteries. Conclusions: We designed and patented an original hemodynamic ex vivo model to further study newDES, as well as a wide range of vascular diseases and medical devices. 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 major benefit will be the reduction of animal experimentation and the opportunity to test new DES or other vascular therapeutics in human tissues (human infrapopliteal or coronary arteries collected during human donation).
- 出版日期2015-11
