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Research Papers

A Hybrid Bioprinting Approach for Scale-Up Tissue Fabrication

[+] Author and Article Information
Yin Yu

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

Yahui Zhang

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

Ibrahim T. Ozbolat

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

1Corresponding author.

Contributed by the Manufacturing Engineering Division of ASME for publication in the JOURNAL OF MANUFACTURING SCIENCE AND ENGINEERING. Manuscript received April 15, 2014; final manuscript received August 23, 2014; published online October 24, 2014. Assoc. Editor: Darrell Wallace.

J. Manuf. Sci. Eng 136(6), 061013 (Oct 24, 2014) (9 pages) Paper No: MANU-14-1196; doi: 10.1115/1.4028511 History: Received April 15, 2014; Revised August 23, 2014

Tissue engineering has been focused on the fabrication of vascularized 3D tissue for decades. Most recently, bioprinting, especially tissue and organ printing, has shown great potential to enable automated robotic-based fabrication of 3D vascularized tissues and organs that are readily available for in vitro studies or in vivo transplantation. Studies have demonstrated the feasibility of the tissue printing process through bioprinting of scaffold-free cellular constructs that are able to undergo self-assembly for tissue formation; however, they are still limited in size and thickness due to the lack of a vascular network. In this paper, we present a framework concept for bioprinting 3D large-scale tissues with a perfusable vascular system in vitro to preserve cell viability and tissue maturation. With the help of a customized Multi-Arm Bioprinter (MABP), we lay out a hybrid bioprinting system to fabricate scale-up tissues and organ models and demonstrated envision its promising application for in vitro tissue engineering and its potential for therapeutic purposes with our proof of concept study.

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Figures

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Fig. 1

Concept of 3D tissue-printing technology: vascular network is printed in tandem with tissue-specific aggregate strands to provide both mechanical support and media perfusion

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Fig. 2

(a) The MABP [18], (b) printed cell aggregate strand, (c) working principle of the MABP with dual operating nozzles in tandem, (d) printed vasculature showing perfusability in a perfusion culture chamber. The printer is located in a vertical flow hood in our clean room facility for the sterilization of the process.

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Fig. 3

(a) A printed vasculature in perfusion chamber under pulsatile flow, (b) a printed vasculature in zigzag shape longer than 80 cm in length demonstrating perfusion in a custom-made perfusion chamber, and (c) a histology image showing collagen and smooth muscle deposition by human umbilical smooth muscle cells in 6 weeks.

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Fig. 4

(a) Fabricated tissue strands, which are mechanically coherent and possess high cell viability. (b) and (c) Fusion of tissue strands under fluorescence microscope, where the gap between tissue strands closes in 7 days. (d) An immunostaining image demonstrating F-actin expression (Note: 4′,6-diamidino-2-phenylindole (DAPI) stained cell nucleus).

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Fig. 5

A representative model of single layer hybrid bioprinting

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Fig. 6

Custom-made perfusion system for fusion and maturation of tissues enclosing the vasculature network. Arrowheads show media flow direction. The whole system can be easily enclosed within an incubator.

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Fig. 7

The concept of capillarization within maturated tissues: cut-away views demonstrate zoom-in view macrovasculatures and cocultured tissue strands, where endothelial cells self-organize and create capillarization under hemodynamically equivalent media flow with required growth factors

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Fig. 8

(a) Demonstration of self-assembly of fibroblast tissue strands around a vasculature supporting pulsatile perfusion, which demonstrates the feasibility of the concept. (b) Zoom-in and (c) cross-sectional view.

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Fig. 9

(a) U-turn section of a vasculature, (b) two tissue strands are printed between two consecutive vasculatures (n = 2), and (c) three tissue strands are printed between two consecutive vasculatures (n = 3)

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