In Vitro Microvessel Growth and Remodeling within a Three-Dimensional Microfluidic Environment
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Kamm_In vitro microvessel.pdf
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Author(s)
Park, Young K.
Tu, Ting-Yuan
Lim, Sei Hien
Clement, Ivan J. M.
Yang, Se Y.
Kamm, Roger Dale
Date Issued
December 2013
Journal
Cellular and Molecular Bioengineering
Publisher
Springer-Verlag
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Singapore-MIT Alliance in Research and Technology (SMART)
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DOI of Published Version
https://doi.org/10.1007/s12195-013-0315-6
