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Engineering of Artificial Lymph Node

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Abstract

Synthetic immunology has been a topic of research in both the immunology and tissue engineering fields. Since the first successful generation of an artificial lymph node (LN) in vivo by implantation of a collagen scaffold with stromal cells has been reported, tissue engineering of artificial LNs using several biological and engineering techniques has started. Recently, the advance engineering approaches using several manufacturing machines, including three-dimensional (3D) printers, 3D fabrication and assembling machines, have been addressed. Such approaches are in general called “Biofabrication”. As the use of machines has several potential capabilities, such as super-manufacturing beyond the capability of humans, direct tissue manufacturing by additive manufacturing and computer aided tissue engineering by applying high efficiency of the computer and digital technologies, the strategy of biofabrication can provide a potential of breakthrough to construct highly sophisticated 3D scaffolds and to generate several complex 3D tissues and organs. Based on this concept, we have ever developed several machines for this purpose such as an inkjet 3D bioprinter to construct complex and multi-composite 3D structures. In the present work, we applied this strategy to rationally design and construct artificial LNs. This research is still in its infancy, and it requires several improvements in terms of new technology. Here, we introduced our struggles and current works towards production of practical artificial LNs.

Keywords

  • Artificial lymph node
  • Synthetic immunology
  • Biofabrication
  • Bioprinting
  • Bio-assembly

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  • DOI: 10.1007/978-4-431-56027-2_9
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Fig. 9.1
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Fig. 9.4
Fig. 9.5
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Abbreviations

LN:

Lymph node

2D:

two dimension or two dimensional

3D:

three dimension or three dimensional

CAD:

computer aided design

CAM:

Computer aided manufacturing

CAE:

Computer aided engineering

AM:

Additive Manufacturing

FDM:

fused deposition modeling

UV:

Ultra violet

PGA:

polyglycolic acid

PLA:

polylactic acid

PCL:

poly-caprolactone

SLOs:

secondary lymphoid organs

TLOs:

tertiary lymphoid organs

LTo:

lymphoid tissue organizer

LTi:

lymphoid tissue inducer

VCAM-1:

vascular cell adhesion molecule-1

DC:

dendritic cell

FDC:

follicular dendritic cell

EC:

endothelial cell

SCID mouse:

severe combined immunodeficiency mouse

ECM:

Extracellular Matrix

MEMS:

Micro Electro Mechanical Systems

GF:

Growth factor

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Acknowledgements

The authors would like to thank the members of the artificial LN project team at Nakamura Laboratory at the University of Toyama and the staff of Kasen Nozzle Mfg. Co. Ltd. for help with the experiments using the spinneret nozzle. We would also like to thank the members of the Grant-in-Aid for Scientific Research on Innovative Areas “Analysis and Synthesis of Multidimensional Immune Organ Network” for important information regarding synthetic immunology. In addition, we express our thanks to Musashi Engineering Inc. and Leica Microsystems K.K. for kindly offering photographs and their kind support for obtaining images. For Fig. 9.9, we are thankful to Professor Shiro Mizoguchi a honorary professor of Kobe University for giving permission of use a figure of the data base of histology of Kobe Gakuin University.

This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Hyper Bio Assembler for 3D Cellular Innovation” (no. 26106713) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and A-STEP (Adaptable & Seamless Technology Transfer Program through Target-driven R&D) from the Japan Science and Technology Agency (no. AS242170P).

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Correspondence to Makoto Nakamura M.D., Ph.D. .

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Nakamura, M. et al. (2016). Engineering of Artificial Lymph Node. In: Watanabe, T., Takahama, Y. (eds) Synthetic Immunology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56027-2_9

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