In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion

We developed a portable microfluidic system that combines spontaneous lumen formation from human umbilical endothelial cells (HUVECs) in fibrin–collagen hydrogels with active perfusion controlled by a braille actuator. Adaptive interstitial flow and feedthrough perfusion switching enabled the succes...

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Main Authors: Kotaro Nishikata, Kimisato Doi, Nobuyoshi Kaneoya, Masataka Nakamura, Nobuyuki Futai
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Micromachines
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Online Access:https://www.mdpi.com/2072-666X/16/1/14
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author Kotaro Nishikata
Kimisato Doi
Nobuyoshi Kaneoya
Masataka Nakamura
Nobuyuki Futai
author_facet Kotaro Nishikata
Kimisato Doi
Nobuyoshi Kaneoya
Masataka Nakamura
Nobuyuki Futai
author_sort Kotaro Nishikata
collection DOAJ
description We developed a portable microfluidic system that combines spontaneous lumen formation from human umbilical endothelial cells (HUVECs) in fibrin–collagen hydrogels with active perfusion controlled by a braille actuator. Adaptive interstitial flow and feedthrough perfusion switching enabled the successful culture of spontaneously formed naturally branched lumens for more than one month. We obtained many large-area (2 mm × 3 mm) long-term (more than 30 days per run) time-lapse image datasets of the in vitro luminal network using this microfluidic system. We also developed an automatic image analysis pipeline to extract the morphology of the lumen network and node–edge network structure weighted with segmentwise flow parameters. The automatic lumen area measurements revealed that almost all lumens were successfully cultured in this system for approximately 50 days, following the meshwork, sprouting, remodeling, stability, and erosion stages. We found that the optimization of the lumen network during the remodeling stage can be explained by the decrease in the betweenness centrality of the WSS-weighted network and the increase in the strength centrality of the flow-rate-weighted network.
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series Micromachines
spelling doaj-art-4554de61dd0c4985acaebadd9a4fa2fe2025-01-24T13:41:50ZengMDPI AGMicromachines2072-666X2024-12-011611410.3390/mi16010014In Vitro Model of Vascular Remodeling Under Microfluidic PerfusionKotaro Nishikata0Kimisato Doi1Nobuyoshi Kaneoya2Masataka Nakamura3Nobuyuki Futai4Department of Mechanical Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Koto-ku, Tokyo 135-8548, JapanDepartment of Mechanical Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Koto-ku, Tokyo 135-8548, JapanDepartment of Mechanical Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Koto-ku, Tokyo 135-8548, JapanDepartment of Mechanical Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Koto-ku, Tokyo 135-8548, JapanDepartment of Mechanical Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Koto-ku, Tokyo 135-8548, JapanWe developed a portable microfluidic system that combines spontaneous lumen formation from human umbilical endothelial cells (HUVECs) in fibrin–collagen hydrogels with active perfusion controlled by a braille actuator. Adaptive interstitial flow and feedthrough perfusion switching enabled the successful culture of spontaneously formed naturally branched lumens for more than one month. We obtained many large-area (2 mm × 3 mm) long-term (more than 30 days per run) time-lapse image datasets of the in vitro luminal network using this microfluidic system. We also developed an automatic image analysis pipeline to extract the morphology of the lumen network and node–edge network structure weighted with segmentwise flow parameters. The automatic lumen area measurements revealed that almost all lumens were successfully cultured in this system for approximately 50 days, following the meshwork, sprouting, remodeling, stability, and erosion stages. We found that the optimization of the lumen network during the remodeling stage can be explained by the decrease in the betweenness centrality of the WSS-weighted network and the increase in the strength centrality of the flow-rate-weighted network.https://www.mdpi.com/2072-666X/16/1/14remodelingspontaneousvascular networkmicrofluidiccentrality
spellingShingle Kotaro Nishikata
Kimisato Doi
Nobuyoshi Kaneoya
Masataka Nakamura
Nobuyuki Futai
In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion
Micromachines
remodeling
spontaneous
vascular network
microfluidic
centrality
title In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion
title_full In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion
title_fullStr In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion
title_full_unstemmed In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion
title_short In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion
title_sort in vitro model of vascular remodeling under microfluidic perfusion
topic remodeling
spontaneous
vascular network
microfluidic
centrality
url https://www.mdpi.com/2072-666X/16/1/14
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