title: Engineering a Blood Vessel Network Module for Body-on-a-Chip Applications.
abstract: The blood circulatory system links all organs from one to another to support and maintain each organ's functions consistently. Therefore, blood vessels have been considered as a vital unit. Engineering perfusable functional blood vessels in vitro has been challenging due to difficulties in designing the connection between rigid macroscale tubes and fragile microscale ones. Here, we propose a generalizable method to engineer a "long" perfusable blood vessel network. To form millimeter-scale vessels, fibroblasts were co-cultured with human umbilical vein endothelial cells (HUVECs) in close proximity. In contrast to previous works, in which all cells were permanently placed within the device, we developed a novel method to culture paracrine factor secreting fibroblasts on an O-ring-shaped guide that can be transferred in and out. This approach affords flexibility in co-culture, where the effects of secreted factors can be decoupled. Using this, blood vessels with length up to 2 mm were successfully produced in a reproducible manner (>90%). Because the vessels form a perfusable network within the channel, simple links to inlets and outlets of the device allowed connections to the outside world. The robust and reproducible formation of in vitro engineered vessels can be used as a module to link various organ components as parts of future body-on-a-chip applications.
authors.affiliation: Institute of Advanced Machinery and Design, Seoul National University, Seoul, Korea School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea.
authors.forename: Hyunryul
authors.initials: H
authors.lastname: Ryu
authors.affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea.
authors.forename: Soojung
authors.initials: S
authors.lastname: Oh
authors.affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea.
authors.forename: Hyun Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, Gyeonggi-do, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, Gyeonggi-do, Korea.
authors.forename: Hae Kwang
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Institute of Advanced Machinery and Design, Seoul National University, Seoul, Korea School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea njeon@snu.ac.kr.
authors.forename: Noo Li
authors.initials: NL
authors.lastname: Jeon
mesh_terms: D001775:Blood Circulation; D001808:Blood Vessels / Q000166:cytology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D056656:Lab-On-A-Chip Devices / Q000706:statistics & numerical data; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D010477:Perfusion; D023822:Tissue Engineering / Q000379:methods*
keywords: blood vessel; body-on-a-chip; microfluidics; screening system; three-dimensional cell culture