Microphysiological Engineering of Self-Assembled and Perfusable Microvascular
Beds for the Production of Vascularized Three-Dimensional Human Microtissues.
Authors Paek J, Park SE, Lu Q, Park KT, Cho M, Oh JM, Kwon KW, Yi YS, Song JW, Edelstein
HI, Ishibashi J, Yang W, Myerson JW, Kiseleva RY, Aprelev P, Hood ED, Stambolian
D, Seale P, Muzykantov VR, Huh D
Submitted By Patrick Seale on 10/14/2019
Status Published
Journal ACS nano
Year 2019
Date Published 7/1/2019
Volume : Pages 13 : 7627 - 7643
PubMed Reference 31194909
Abstract The vasculature is an essential component of the circulatory system that plays a
vital role in the development, homeostasis, and disease of various organs in the
human body. The ability to emulate the architecture and transport function of
blood vessels in the integrated context of their associated organs represents an
important requirement for studying a wide range of physiological processes.
Traditional in vitro models of the vasculature, however, largely fail to offer
such capabilities. Here we combine microfluidic three-dimensional (3D) cell
culture with the principle of vasculogenic self-assembly to engineer perfusable
3D microvascular beds in vitro. Our system is created in a micropatterned
hydrogel construct housed in an elastomeric microdevice that enables coculture
of primary human vascular endothelial cells and fibroblasts to achieve de novo
formation, anastomosis, and controlled perfusion of 3D vascular networks. An
open-top chamber design adopted in this hybrid platform also makes it possible
to integrate the microengineered 3D vasculature with other cell types to
recapitulate organ-specific cellular heterogeneity and structural organization
of vascularized human tissues. Using these capabilities, we developed stem
cell-derived microphysiological models of vascularized human adipose tissue and
the blood-retinal barrier. Our approach was also leveraged to construct a 3D
organotypic model of vascularized human lung adenocarcinoma as a high-content
drug screening platform to simulate intravascular delivery, tumor-killing
effects, and vascular toxicity of a clinical chemotherapeutic agent.
Furthermore, we demonstrated the potential of our platform for applications in
nanomedicine by creating microengineered models of vascular inflammation to
evaluate a nanoengineered drug delivery system based on active targeting
liposomal nanocarriers. These results represent a significant improvement in our
ability to model the complexity of native human tissues and may provide a basis
for developing predictive preclinical models for biopharmaceutical applications.