On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures.

Tao Yue,Yuanyuan Liu,Yan Peng,Toshio Fukuda,Jun Luo,Masaru Takeuchi,Shaorong Xie,Na Liu,Qiang Huang

doi:10.3390/mi10120840

Abstract

Multilayered and multicellular structures are indispensable for constructing functional artificial tissues. Engineered vascular-like microstructures with multiple layers are promising structures to be functionalized as artificial blood vessels. In this paper, we present an efficient method to construct multilayer microtubes embedding different microstructures based on direct fabrication and assembly inside a microfluidic device. This four-layer microfluidic device has two separate inlets for fabricating various microstructures. We have achieved alternating-layered microtubes by controlling the fabrication, flow, and assembly time of each microstructure, and as well, double-layered microtubes have been built by a two-step assembly method. Modifications of both the inner and outer layers was successfully demonstrated, and the flow conditions during the on-chip assembly were evaluated and optimized. Each microtube was successfully constructed within several minutes, showing the potential applications of the presented method for building engineered vascular-like microstructures with high efficiency.

Highlights

Cellular structures follow certain patterns and shapes inside tissues and organs, such as muscle, skin, liver, and blood vessel [1,2]
As an indispensable component for building functional artificial tissues, many researchers in tissue engineering and regeneration medicine have been focusing on building engineered vascular-like structures [4,5,6]
Alternating-Layered Microtubes are Assembled by Controlling the Fabrication, Flow, and Assembling Sequences On-Chip

Summary

Introduction

Cellular structures follow certain patterns and shapes inside tissues and organs, such as muscle, skin, liver, and blood vessel [1,2]. Direct printing of cell-embedded microstructures and their assembly to large tissues are creative ways to build large tissue-like three-dimensional (3D) cell structures [21]. Direct formation of microtubes using microfluidic channels is possible for generating vascular-like cellular structures and networks [26,27], the unchangeable channel shape limits the control flexibility after the device is fabricated. Simple vascular-like microtubes have been assembled inside microfluidic channel [43] These simple vascular-like hollow microtubes have contained only one type of cell, which limits their practical functionalization as artificial vascular structures. The aasssseemmbbllyymmeeththooddfofrorthtehdeoduobuleb-llea-ylaeryeedremdicmroicturobteusb, einsc, liundcilnugditnhge athsseemasbsleymobfltyheofouthteer oFlauiygteeurrrleaasy4te.hrTeahfisertshatsestfeeimrpsbt(lasy)teampned(ath)thoaednidfnontrheetrhilenayndeorualbasylteeh-rleaayssectrhoedendsmescitocernpodt(ubsb)t.eep(sc, )(ibTn)ch. le(ucds)ciTnhhgeemtshacethiceamsdsraeatmwicbidnlyrgaoowffitnhge ooafsutstheemer albaslyseedmrdabosluetdbhlede-foliaursybtelesret-eldapym(eairc)erdaontmudbictehr.oetiunbnee.r layer as the second step (b). (c) The schematic drawing of the assembled double-layered microtube

Viability Evaluation of Cells Encapsulated Inside Microstructures

Data Acquisition and Analysis

Results and Discussion