An ex vivo physiologic and hyperplastic vessel culture model to study intra-arterial stent therapies

Conventional in vitro methods for biological evaluation of intra-arterial devices such as stents fail to accurately predict cytotoxicity and remodeling events. An ex vivo flow-tunable vascular bioreactor system (VesselBRx), comprising intra- and extra-luminal monitoring capabilities, addresses these...

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Bibliographic Details
Published inBiomaterials Vol. 275; p. 120911
Main Authors Wang, Juan, Kural, Mehmet H., Wu, Jonathan, Leiby, Katherine L., Mishra, Vinayak, Lysyy, Taras, Li, Guangxin, Luo, Jiesi, Greaney, Allison, Tellides, George, Qyang, Yibing, Huang, Nan, Niklason, Laura E.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.08.2021
Subjects
Absorbable Implants
Animals
Cell apoptosis
Coronary Vessels
Hyperplasia
Hyperplasia - pathology
Local microenvironment
Magnesium stent
Rabbits
Stents
Swine
Tunica Intima - pathology
Vessel bioreactor
Vessel bioreactor
Local microenvironment
Hyperplasia
Magnesium stent
Cell apoptosis
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Summary:Conventional in vitro methods for biological evaluation of intra-arterial devices such as stents fail to accurately predict cytotoxicity and remodeling events. An ex vivo flow-tunable vascular bioreactor system (VesselBRx), comprising intra- and extra-luminal monitoring capabilities, addresses these limitations. VesselBRx mimics the in vivo physiological, hyperplastic, and cytocompatibility events of absorbable magnesium (Mg)-based stents in ex vivo stent-treated porcine and human coronary arteries, with in-situ and real-time monitoring of local stent degradation effects. Unlike conventional, static cell culture, the VesselBRx perfusion system eliminates unphysiologically high intracellular Mg2+ concentrations and localized O2 consumption resulting from stent degradation. Whereas static stented arteries exhibited only 20.1% cell viability and upregulated apoptosis, necrosis, metallic ion, and hypoxia-related gene signatures, stented arteries in VesselBRx showed almost identical cell viability to in vivo rabbit models (~94.0%). Hyperplastic intimal remodeling developed in unstented arteries subjected to low shear stress, but was inhibited by Mg-based stents in VesselBRx, similarly to in vivo. VesselBRx represents a critical advance from the current static culture standard of testing absorbable vascular implants.
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J. Wang conceived the study, designed, and optimized all the experiments, analyzed the data, and prepared the manuscript. M.H.K. helped to design and assemble bioreactors and developed the real-time monitoring method. J. Wu analyzed RNA data and assisted to prepare the manuscript. K. L. prepared RNA samples and discussed the manuscript. V. M. stained some of samples. T. L. and G. L. harvested and isolated porcine coronary arteries. J. L. suggested to use porcine coronary artery for this study. A. G. discussed RNA data. G. T. harvested and isolated human coronary arteries. Y.Q. provided a deep discussion. N. H. provided Mg-based stents and surgical planform of rabbit tests. L. E. N. provided the guidance, funding, obstacle removal, and interpretation of results.
Contributions
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2021.120911