Integrating perfusable vascular networks with a three-dimensional tissue in a microfluidic device

Abstract

Creating vascular networks in tissues is crucial for tissue engineering. Although recent studies have demonstrated the formation of vessel-like structures in a tissue model, long-term culture is still challenging due to the lack of active perfusion in vascular networks. Here, we present a method to create a three-dimensional cellular spheroid with a perfusable vascular network in a microfluidic device. By the definition of the cellular interaction between human lung fibroblasts (hLFs) in a spheroid and human umbilical vein endothelial cells (HUVECs) in microchannels, angiogenic sprouts were induced from microchannels toward the spheroid; the sprouts reached the vessel-like structures in a spheroid to form a continuous lumen. We demonstrated that the vascular network could administer biological substances to the interior of the spheroid. As cell density in the spheroid is similar to that of a tissue, the perfusable vasculature model opens up new possibilities for a long-term tissue culture in vitro.

Recapitulating the Vasculature Using Organ-On-Chip Technology

“…A similar chip design was used for investigating the effects of physical cues on sprouting; in this case, interstitial flow was generated that promoted sprouting against the direction of the flow [21]. These type of systems have also been used in the research on tumour vasculature and the effect of different drugs on the vasculature and tumour progression [75][76][77][78][79].…”

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

“…Coculture Arrangement in Microfluidic Device : The coculture of ECs with supporting cells can be achieved by using several microfluidic design elements: simple integration of heterotypic cell types in the same channel to mimic juxtacrine signaling; separate channels on either side with different cells seeded to mimic paracrine signaling; one cell type placed on top of the other; and incorporation of the supporting cells into the tissue constructs . For these methods, both cell types can either be seeded at the same time, or one cell type can be seeded first, left to attach and stabilize, and the other seeded at an appropriate later time.…”

“…A) Integration of a perfusable vasculature and spheroid in a microfluidic device through the angiogenesis process. Reproduced with permission . Copyright 2017, Oxford University Press.…”

Intracellular Electrochemical Sensing

“…Promisingly, electrochemical approaches can be combined with organ‐on‐a‐chip systems, which mimic organs in microfluidics . Since the vascular system is important for organs, vascular constructions have been already incorporated into organs‐on‐a‐chip . Consequently, the function of the vascular system can be electrochemically evaluated in such organs‐on‐a‐chip, e. g., as shown by monitoring of nitric oxide (NO) release by endothelial cells .…”