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Research Papers

Direct Bioprinting of Vessel-Like Tubular Microfluidic Channels

[+] Author and Article Information
Yahui Zhang

BioMfG Laboratory,
Center for Computer-Aided Design,
The University of Iowa,
Iowa City, IA 52242;
Department of Mechanical and Industrial Engineering,
The University of Iowa,
Iowa City, IA 52242

Yin Yu

BioMfG Laboratory,
Center for Computer-Aided Design,
The University of Iowa,
Iowa City, IA 52242;
Department of Biomedical Engineering,
The University of Iowa,
Iowa City, IA 52242

Ibrahim T. Ozbolat

BioMfG Laboratory,
Center for Computer-Aided Design,
The University of Iowa,
Iowa City, IA 52242;
Department of Mechanical and Industrial Engineering,
The University of Iowa,
Iowa City, IA 52242
e-mail: ibrahim-ozbolat@uiowa.edu

1Corresponding author.

Manuscript received February 15, 2012; final manuscript received April 26, 2013; published online July 23, 2013. Assoc. Editor: Shaurya Prakash.

J. Nanotechnol. Eng. Med 4(2), 020902 (Jul 23, 2013) (7 pages) Paper No: NANO-13-1008; doi: 10.1115/1.4024398 History: Received February 15, 2013; Revised April 26, 2013

Despite the progress in tissue engineering, several challenges must be addressed for organ printing to become a reality. The most critical challenge is the integration of a vascular network, which is also a problem that the majority of tissue engineering technologies are facing. An embedded microfluidic channel network is probably the most promising solution to this problem. However, the available microfluidic channel fabrication technologies either have difficulty achieving a three-dimensional complex structure or are difficult to integrate within cell printing process in tandem. In this paper, a novel printable vessel-like microfluidic channel fabrication method is introduced that enables direct bioprinting of cellular microfluidic channels in form of hollow tubes. Alginate and chitosan hydrogels were used to fabricate microfluidic channels showing the versatility of the process. Geometric characterization was performed to understand effect of biomaterial and its flow rheology on geometric properties. Microfluidic channels were printed and embedded within bulk hydrogel to test their functionality through perfusion of cell type oxygenized media. Cell viability experiments were conducted and showed great promise of the microfluidic channels for development of vascular networks.

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Figures

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Fig. 1

A representative image of (a) the experimental setup and (b) coaxial nozzle assembly with fluid flow paths for hydrogel and crosslinker solutions. The coaxial system consists of three parts: inner tube, feed tube and outer tube.

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Fig. 2

Media perfusion system in an incubator: (a) culture media reservoir with capacity of 1 l, (b) digital pump, (c) media perfused cellular microfluidic channel; (d) three-axis motion stages, and (e) cell and tissue culture incubator

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Fig. 8

Embedding microfluidic channels in bulk hydrogels. (a) alginate microfluidic channel embedded in bulk alginate displayed well-defined structure, and was able to transport media smoothly without any swirling formation (arrows indicate media flow direction); (b) two layers of alginate channels with multidirectional media perfusion (flow) (with red and green food dye); (c) alginate microfluidic channel embedded in bulk chitosan displayed well-defined pattern but ruptures were observed at respective locations along channels (circled sections), and (d) chitosan-microfluidic structure failed to transport media smoothly due to disrupted channels.

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Fig. 7

Media perfusion and cell viability analysis: (a) perfusion of cell culture media through zigzag patterned channel showed no blockage or disturbance; (b) intentionally generated air bubbles illustrate media flow through the hollow feature of printed channels; (c) cells were uniformly distributed throughout the channel wall; (d) quantifiable cell death was observed along the microfluidic channel, but most of the cells were viable; (e) cell viability was around 62.7 ± 0.05% after 12 h of media perfusion

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Fig. 6

Effect of flow rheology on the geometry of microfluidic channels: varying (a) alginate dispensing rate, (b) CaCl2 dispensing rate, (c) chitosan dispensing rate, and (d) sodium hydroxide dispensing rate (single asterisk (*) indicates significant differences between groups (p < 0.05))

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Fig. 5

(a) Partially crosslinked alginate (b) and (c) relatively weak structure bent and collapsed due to small wall thickness

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Fig. 4

Geometric comparison of printed microfluidic channels per variation in hydrogel concentrations including: (a) chitosan, and (b) alginate (single asterisk (*) indicates significant differences between groups (p < 0.05))

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Fig. 3

Printed microfluidic channels: (a) alginate microfluidic channels have acceptable mechanical strength and structural integrity, (b) chitosan-microfluidic channels are fragile and easy to rupture, and (c) printed eight-layer alginate microfluidic channel network with well-defined morphology

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