Angiogenic Sprouting Dynamics Mediated by Endothelial‐Fibroblast Interactions in Microfluidic Systems

Abstract

Angiogenesis, the development of new blood vessels from existing vasculature, is a key process in normal development and pathophysiology. In vitro models are necessary for investigating mechanisms of angiogenesis and developing antiangiogenic therapies. Microfluidic cell culture models of angiogenesis are favored for their ability to recapitulate 3D tissue structures and control spatiotemporal aspects of the microenvironments. To capture the angiogenesis process, microfluidic models often include endothelial cells and a fibroblast component. However, the influence of fibroblast organization on resulting angiogenic behavior remains unclear. Here a comparative study of angiogenic sprouting on a microfluidic chip induced by fibroblasts in 2D monolayer, 3D dispersed, and 3D spheroid culture formats, is conducted. Vessel morphology and sprout distribution for each configuration are measured, and these observations are correlated with measurements of secreted factors and numerical simulations of diffusion gradients. The results demonstrate that angiogenic sprouting varies in response to fibroblast organization with correlating variations in secretory profile and secreted factor gradients across the microfluidic device. This study is anticipated to shed light on how sprouting dynamics are mediated by fibroblast configuration such that the microfluidic cell culture design process includes the selection of a fibroblast component where the effects are known and leveraged.

Microfluidic Droplet-Assisted Fabrication of Vessel-Supported Tumors for Preclinical Drug Discovery

“…Hydrostatic pressure was provided to promote vessel network formation (Figure A). The left flow channel was applied with a high liquid column (300 μL), and the right flow channel was applied with a low liquid column (100 μL), so that there was a hydrostatic pressure gradient across the central 3D fibrin hydrogel . The preformed cell-laden beads were mixed in the HUVEC suspension for vascularization.…”

Replacement in angiogenesis research: Studying mechanisms of blood vessel development by animal-free in vitro, in vivo and in silico approaches

“…These systems provide easily accessible, standardized conditions with spatiotemporal control of (bio)chemical and physical stimuli ( Nishimura et al, 2020 ). In basic angiogenesis research, they have been broadly used to study the impact of hemodynamic forces ( Akbari et al, 2019 ; Arpino et al, 2021 ; Zhao et al, 2021 ) as well as cell-cell ( Amemiya et al, 2021 ; Bai et al, 2021 ; Walji et al, 2021 ) and cell-matrix interactions ( Wang W. Y. et al, 2021 ; Liu et al, 2021 ) on the mechanisms of blood vessel development. Moreover, they represent attractive tools for the high-throughput screening of anti-angiogenic drugs ( Kim et al, 2015 ; Sobrino et al, 2016 ; Kim et al, 2021 ) ( Figure 3 ).…”

Bidirectional airflow in lung airway-on-a-chip with matrix-derived membrane elicits epithelial glycocalyx formation

“…Organ-on-a-chip technology has emerged over the past decade as advanced in vitro models that can recapitulate key tissue and organ functions in microfluidic devices. [36][37][38][39][40] Various lung-on-a-chip devices have introduced successful physiological models of the lung airway microenvironment, [41][42][43][44] including several lung-on-a-chip disease models for asthma, pulmonary edema, lung cancer, mechanical injury to the epithelium, and SARS-CoV2 infection. [45][46][47][48][49] Our group has reported two airway-on-a-chip studies.…”