Computer-assisted designing and biofabrication of 3-D hydrogel structures towards thick 3-D tissue engineering
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Computer-assisted designing and biofabrication of 3-D hydrogel structures towards thick 3-D tissue engineering Makoto Nakamura, Kenichi Arai, Hideki Toda, Shintaroh Iwanaga, Kozo Ito, Capi Genci, and Toshio Nikaido Graduate school of Science and Engineering for Research, University of Toyama 3190 Gofuku, Toyama 930-8555, Japan E-mail: [email protected]
ABSTRACT Engineering and manufacturing of thick and bio-functional tissue products is one of the big issues in tissue engineering. To produce such tissues, we need some innovative technologies, which enable us to build up thick, three-dimensional structures and to arrange multiple types of cells to make complicated tissue structures. Based on such considerations, we have developed a custom-made inkjet 3D bioprinter, which realized both of direct cell printing and 3D laminating printing with cells and hydrogel. Recently, it has been improved, and here we report recent progresses and our achievements with new version 3D bioprinter. Image based printing mode and active Z-axis control system were added. As a useful structure, an image of multi-honeycomb pattern was designed in computer and next it was copied and finally in total 100 image data were prepared. Using those digital data, 3D image of thick multi-honeycomb structure was reconstructed in computer, and then, laminating printing was carried out using our new version 3D bioprinter with alginate hydrogel. The new version printer showed good performance of 3D laminating printing and finally complicated 3D multihoneycomb hydrogel structures could be successfully fabricated. It is indicated that fabrication of cell containing 3D structures based on the computer aided designs is feasible and that such biofabrication technologies must contribute to further innovative advancement of tissue engineering. INTRODUCTION Tissue engineering and regenerative medicine have been developed as one of the innovative biomedical technologies towards 21st. century. Clinical application of engineered tissues by those technologies has been realized in several tissues such as skin, cornea and cartilage. However, there are still big obstacles to succeed in engineering many of major organs, such as heart, liver and kidney. Based on the histological considerations, the fundamental differences between the achieved tissues and the unachieved tissues are summarized in table 1, in 4 categories: (1) Structures, (2) Heterogeneity, (3) Thickness, (4) Vasculature [1, 2]. Those histological differences indicate the difficulties in present tissue engineering, too, and simultaneously show us the essential issues to be overcome and the directions for the technological developments.
Table I. Histological difference between achieved tissues and non-achieved tissues in tissue engineering. Achieved tissues
Unachieved tissues
(1) Structures
Simple tissues with no significant structures
Complicated tissues with characteristic microscaled structures for respective organs
(2) Heterogeneity
Tissues with mono-cell type
Heterogeneous composite tis
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