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A 3D bioprinting system to produce human-scale tissue constructs with structural integrity

Nature Biotechnology volume 34, pages 312319 (2016) | Download Citation

Abstract

A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue–organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100–200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.

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Acknowledgements

This work was supported, in part, by grants from the Armed Forces Institute of Regenerative Medicine (W81XWH-08-2-0032), the Telemedicine and Advanced Technology Research Center at the US Army Medical Research and Material Command (W81XWH-07-1-0718) and the Defense Threat Reduction Agency (N66001-13-C-2027). We would like to thank D.M. Eckman for editorial comments on this manuscript, and H.S. Kim and G.V. Kulkarni for technical assistance.

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  1. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.

    • Hyun-Wook Kang
    • , Sang Jin Lee
    • , In Kap Ko
    • , Carlos Kengla
    • , James J Yoo
    •  & Anthony Atala

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Contributions

H.-W.K., S.J.L., J.J.Y. and A.A. developed the concept of the integration tissue and organ printing (ITOP) system and designed all experiments. H.-W.K. performed in vitro experiments and composite hydrogel development, analyzed data and wrote the manuscript. C.K. performed in vivo experiments of the printed cartilage and bone constructs and analyzed data. I.K.K. performed in vivo experiments of the printed skeletal muscle construct and analyzed data. S.J.L., J.J.Y. and A.A. analyzed data and wrote the manuscript. A.A. provided direction and supervised the project. S.J.L., J.J.Y. and A.A. edited the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Anthony Atala.

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https://doi.org/10.1038/nbt.3413

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