title: In VitroMicrovessel Growth and Remodeling within a Three-dimensional Microfluidic Environment.
abstract: This paper presentsin vitromicrovascular 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 conditions of collagen gel scaffolds (2.0 mg/ml, 2.5 mg/ml, and 3.0 mg/ml), the number of skeleton within collagen gel scaffolds was consistently the highest (3.0 mg/ml), followed by those of collagen gel scaffolds (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 d 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 d. Finally, early steps in the maturation process of microvascular networks for 14 d were characterized by demonstrating sequential steps of branching, expanding, remodeling, pruning, and clear delineation of lumens within fibrin gel scaffolds. Our findings demonstrate anin vitromodel 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.
authors.affiliation: Biosystems & Micromechanics IRG, Singapore-MIT Alliance for Research and Technology Center, Singapore 117543 ; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Young K
authors.initials: YK
authors.lastname: Park
authors.affiliation: Biosystems & Micromechanics IRG, Singapore-MIT Alliance for Research and Technology Center, Singapore 117543.
authors.forename: Ting-Yuan
authors.initials: TY
authors.lastname: Tu
authors.affiliation: Biosystems & Micromechanics IRG, Singapore-MIT Alliance for Research and Technology Center, Singapore 117543.
authors.forename: Sei Hien
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Computational Biology Programme, Department of Biological Sciences, National University of Singapore, Singapore 119077.
authors.forename: Ivan J M
authors.initials: IJ
authors.lastname: Clement
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Se Y
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Biosystems & Micromechanics IRG, Singapore-MIT Alliance for Research and Technology Center, Singapore 117543 ; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA ; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
keywords: 3D gel scaffolds; 3D microfluidic platform; Collagen gel; Fibrin gel; Microvascular network formation