In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment

This paper presents in vitro microvascular network formation within 3D gel scaffolds made from different concentrations of type-I collagen, fibrin, or a mixture of collagen and fibrin, using a simple microfluidic platform. Initially, microvascular network formation of human umbilical vein endothelia...

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Main Authors: Park, Young K., Tu, Ting-Yuan, Lim, Sei Hien, Clement, Ivan J. M., Yang, Se Y., Kamm, Roger Dale
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Springer-Verlag 2015
Online Access:http://hdl.handle.net/1721.1/97507
https://orcid.org/0000-0002-7232-304X
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author Park, Young K.
Tu, Ting-Yuan
Lim, Sei Hien
Clement, Ivan J. M.
Yang, Se Y.
Kamm, Roger Dale
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Park, Young K.
Tu, Ting-Yuan
Lim, Sei Hien
Clement, Ivan J. M.
Yang, Se Y.
Kamm, Roger Dale
author_sort Park, Young K.
collection MIT
description This paper presents in vitro microvascular network formation within 3D gel scaffolds made from different concentrations of type-I collagen, fibrin, or a mixture of collagen and fibrin, using a simple microfluidic platform. Initially, microvascular network formation of human umbilical vein endothelial cells was examined using live time-lapse confocal microscopy every 90 min from 3 h to 12 h after seeding within three different concentrations of collagen gel scaffolds. Among the three collagen gel concentrations, the number of skeletons was consistently the highest at 3.0 mg/mL, followed by those of collagen gel scaffolds at 2.5 mg/mL and 2.0 mg/mL. Results demonstrated that concentration of collagen gel scaffolds, which influences matrix stiffness and ligand density, may affect microvascular network formation during the early stages of vasculogenesis. In addition, the maturation of microvascular networks in monoculture under different gel compositions within gel scaffolds (2.5 mg/mL) was examined for 7 days using live confocal microscopy. It was confirmed that pure fibrin gel scaffolds are preferable to collagen gel or collagen/fibrin combinations, significantly reducing matrix retractions during maturation of microvascular networks for 7 days. Finally, early steps in the maturation process of microvascular networks for 14 days were characterized by demonstrating sequential steps of branching, expanding, remodeling, pruning, and clear delineation of lumens within fibrin gel scaffolds. Our findings demonstrate an in vitro model for generating mature microvascular networks within 3D microfluidic fibrin gel scaffolds (2.5 mg/mL), and furthermore suggest the importance of gel concentration and composition in promoting the maturation of microvascular networks.
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spelling mit-1721.1/975072022-10-01T15:36:44Z In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment Park, Young K. Tu, Ting-Yuan Lim, Sei Hien Clement, Ivan J. M. Yang, Se Y. Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Singapore-MIT Alliance in Research and Technology (SMART) Park, Young K. Yang, Se Y. Kamm, Roger Dale This paper presents in vitro microvascular network formation within 3D gel scaffolds made from different concentrations of type-I collagen, fibrin, or a mixture of collagen and fibrin, using a simple microfluidic platform. Initially, microvascular network formation of human umbilical vein endothelial cells was examined using live time-lapse confocal microscopy every 90 min from 3 h to 12 h after seeding within three different concentrations of collagen gel scaffolds. Among the three collagen gel concentrations, the number of skeletons was consistently the highest at 3.0 mg/mL, followed by those of collagen gel scaffolds at 2.5 mg/mL and 2.0 mg/mL. Results demonstrated that concentration of collagen gel scaffolds, which influences matrix stiffness and ligand density, may affect microvascular network formation during the early stages of vasculogenesis. In addition, the maturation of microvascular networks in monoculture under different gel compositions within gel scaffolds (2.5 mg/mL) was examined for 7 days using live confocal microscopy. It was confirmed that pure fibrin gel scaffolds are preferable to collagen gel or collagen/fibrin combinations, significantly reducing matrix retractions during maturation of microvascular networks for 7 days. Finally, early steps in the maturation process of microvascular networks for 14 days were characterized by demonstrating sequential steps of branching, expanding, remodeling, pruning, and clear delineation of lumens within fibrin gel scaffolds. Our findings demonstrate an in vitro model for generating mature microvascular networks within 3D microfluidic fibrin gel scaffolds (2.5 mg/mL), and furthermore suggest the importance of gel concentration and composition in promoting the maturation of microvascular networks. Singapore-MIT Alliance for Research and Technology 2015-06-22T18:37:10Z 2015-06-22T18:37:10Z 2013-12 2013-07 Article http://purl.org/eprint/type/JournalArticle 1865-5025 1865-5033 http://hdl.handle.net/1721.1/97507 Park, Young K., Ting-Yuan Tu, Sei Hien Lim, Ivan J. M. Clement, Se Y. Yang, and Roger D. Kamm. “In Vitro Microvessel Growth and Remodeling Within a Three-Dimensional Microfluidic Environment.” Cellular and Molecular Bioengineering 7, no. 1 (December 3, 2013): 15–25. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1007/s12195-013-0315-6 Cellular and Molecular Bioengineering Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer-Verlag PMC
spellingShingle Park, Young K.
Tu, Ting-Yuan
Lim, Sei Hien
Clement, Ivan J. M.
Yang, Se Y.
Kamm, Roger Dale
In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
title In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
title_full In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
title_fullStr In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
title_full_unstemmed In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
title_short In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
title_sort in vitro microvessel growth and remodeling within a three dimensional microfluidic environment
url http://hdl.handle.net/1721.1/97507
https://orcid.org/0000-0002-7232-304X
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