A promising protocol for the endothelialization of vascular grafts in an instrumented rotating bioreactor towards clinical application

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  • NIFE - Lower Saxony Centre for Biomedical Engineering, Implant Research and Development
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Original languageEnglish
Article number109095
JournalBiochemical engineering journal
Volume200
Early online date27 Sept 2023
Publication statusPublished - Nov 2023

Abstract

Pre-endothelialization of a tissue-engineered vascular graft before implantation aims to prevent thrombosis and immunoreactions. This work demonstrates a standardized cultivation process to build a confluent monolayer with human aortal endothelial cells on xenogenous scaffolds. Pre-tested dynamic cultivation conditions in flow slides with pulsatile flow (1 Hz) representing arterial wall conditions were transferred to a newly designed multi-featured rotational bioreactor system. The medium was thickened with 1% methyl cellulose simulating a non-Newtonian fluid comparable to blood. Computational fluid dynamics was used to estimate the optimal volume flow and medium distribution inside the bioreactor chamber for defined wall-near shear stress levels. Flow measurements were performed during cultivation for constant monitoring of the process. Three decellularized porcine arteries were seeded and cultivated in the bioreactor over six days. 1% MC turned out to be the optimal percentage to achieve shear stress values ranging up to 10 dyn/cm 2. Vascular endothelial cells formed a continuous monolayer with significant cell alignment in the direction of flow. The presented cultivation protocol in the bioreactor system thus displays a promising template for graft endothelialization and cultivation. Therefore, establishing a key step for future tissue-engineered vascular graft development with a view towards clinical application.

Keywords

    Bioreactor system, Cell alignment, Dynamic cultivation, Endothelialization, Shear stress, Vascular graft

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A promising protocol for the endothelialization of vascular grafts in an instrumented rotating bioreactor towards clinical application. / Heene, Sebastian; Renzelmann, Jannis; Müller, Caroline et al.
In: Biochemical engineering journal, Vol. 200, 109095, 11.2023.

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abstract = "Pre-endothelialization of a tissue-engineered vascular graft before implantation aims to prevent thrombosis and immunoreactions. This work demonstrates a standardized cultivation process to build a confluent monolayer with human aortal endothelial cells on xenogenous scaffolds. Pre-tested dynamic cultivation conditions in flow slides with pulsatile flow (1 Hz) representing arterial wall conditions were transferred to a newly designed multi-featured rotational bioreactor system. The medium was thickened with 1% methyl cellulose simulating a non-Newtonian fluid comparable to blood. Computational fluid dynamics was used to estimate the optimal volume flow and medium distribution inside the bioreactor chamber for defined wall-near shear stress levels. Flow measurements were performed during cultivation for constant monitoring of the process. Three decellularized porcine arteries were seeded and cultivated in the bioreactor over six days. 1% MC turned out to be the optimal percentage to achieve shear stress values ranging up to 10 dyn/cm 2. Vascular endothelial cells formed a continuous monolayer with significant cell alignment in the direction of flow. The presented cultivation protocol in the bioreactor system thus displays a promising template for graft endothelialization and cultivation. Therefore, establishing a key step for future tissue-engineered vascular graft development with a view towards clinical application.",
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author = "Sebastian Heene and Jannis Renzelmann and Caroline M{\"u}ller and Nils Stanislawski and Fabian Cholewa and Pia Moosmann and Holger Blume and Cornelia Blume",
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AU - Heene, Sebastian

AU - Renzelmann, Jannis

AU - Müller, Caroline

AU - Stanislawski, Nils

AU - Cholewa, Fabian

AU - Moosmann, Pia

AU - Blume, Holger

AU - Blume, Cornelia

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N2 - Pre-endothelialization of a tissue-engineered vascular graft before implantation aims to prevent thrombosis and immunoreactions. This work demonstrates a standardized cultivation process to build a confluent monolayer with human aortal endothelial cells on xenogenous scaffolds. Pre-tested dynamic cultivation conditions in flow slides with pulsatile flow (1 Hz) representing arterial wall conditions were transferred to a newly designed multi-featured rotational bioreactor system. The medium was thickened with 1% methyl cellulose simulating a non-Newtonian fluid comparable to blood. Computational fluid dynamics was used to estimate the optimal volume flow and medium distribution inside the bioreactor chamber for defined wall-near shear stress levels. Flow measurements were performed during cultivation for constant monitoring of the process. Three decellularized porcine arteries were seeded and cultivated in the bioreactor over six days. 1% MC turned out to be the optimal percentage to achieve shear stress values ranging up to 10 dyn/cm 2. Vascular endothelial cells formed a continuous monolayer with significant cell alignment in the direction of flow. The presented cultivation protocol in the bioreactor system thus displays a promising template for graft endothelialization and cultivation. Therefore, establishing a key step for future tissue-engineered vascular graft development with a view towards clinical application.

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