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3D printer tissue engineering


3D Bioprinting of Living Tissues

Progress in drug testing and regenerative medicine could greatly benefit from laboratory-engineered human tissues built of a variety of cell types with precise 3D architecture. But production of greater than millimeter sized human tissues has been limited by a lack of methods for building tissues with embedded life-sustaining vascular networks.

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In this video, the Wyss Institute and Harvard SEAS team uses a customizable 3D bioprinting method to build a thick vascularized tissue structure comprising human stem cells, collective matrix, and blood vessel endothelial cells. Their work sets the stage for advancement of tissue replacement and tissue engineering techniques. Credit: Lewis Lab, Wyss Institute at Harvard University

Multidisciplinary research at the Wyss Institute has led to the development of a multi-material 3D bioprinting method that generates vascularized tissues composed of living human cells that are nearly ten-fold thicker than previously engineered tissues and that can sustain their architecture and function for upwards of six weeks. The method uses a customizable, printed silicone mold to house and plumb the printed tissue on a chip. Inside this mold, a grid of larger vascular channels containing living endothelial cells in silicone ink is printed, into which a self-supporting ink containing living mesenchymal stem cells (MSCs) is layered in a separate print job. After printing, a liquid composed of fibroblasts and extracellular matrix is used to fill open regions within the construct, adding a connective tissue component that cross-links and further stabilizes the entire structure.

Confocal microscopy image showing a cross-section of a 3D-printed, 1-centimeter-thick vascularized tissue construct showing stem cell differentiation towards development of bone cells, following one month of active perfusion of fluids, nutrients, and cell growth factors. The structure was fabricated using a novel 3D bioprinting strategy invented by Jennifer Lewis and her team at the Wyss Institute and Harvard SEAS. Credit: Lewis Lab, Wyss Institute at Harvard University

The resulting soft tissue structure can be immediately perfused with nutrients as well as growth and differentiation factors via a single inlet and outlet on opposite ends of the chip that connect to the vascular channel to ensure survival and maturation of the cells. In a proof-of-principle study, one centimeter thick bioprinted tissue constructs containing human bone marrow MSCs surrounded by connective tissue and supported by an artificial endothelium-lined vasculature, allowed the circulation of bone growth factors and, subsequently, the induction of bone development.

This innovative bioprinting approach can be modified to create various vascularized 3D tissues for regenerative medicine and drug testing endeavors. The Wyss team is also investigating the use of 3D bioprinting to fabricate new versions of the Institute’s organs on chips devices, which makes their manufacturing process more automated and enables development of increasingly complex microphysiological devices. This effort has resulted in the first entirely 3D-printed organ on a chip – a heart on a chip – with integrated soft strain sensors.

  • 1/7 Cross section of long-term perfusion of HUVEC-lined (red) vascular network supporting HNDFladen (green) matrix.
  • 2/7 Top-down view of long-term perfusion of HUVEC-lined (red) vascular network supporting HNDFladen (green) matrix.
  • 3/7 Photograph cross section of printed tissue construct housed within a perfusion chamber.
  • 4/7 Photograph cross section of printed tissue construct housed within a perfusion chamber.
  • 5/7 Photograph of a printed tissue construct housed within a perfusion chamber.
  • 6/7 Photograph of vasculature network and cell inks.
  • 7/7 Photograph of 3D printed vasculature network (red) within Red is the
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3D printing in tissue engineering: a state of the art review of technologies and biomaterials

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Nataraj Poomathi (Department of Mechanical Engineering, Centre for Nanofibers and Nanotechnology Initiative, National University of Singapore, Singapore and Organic and Bioorganic Chemistry Division, CSIR-Central Leather Research Institute, Chennai, India)

Sunpreet Singh (Department of Mechanical Engineering, National University of Singapore, Singapore)

Chander Prakash (School of Mechanical Engineering, Manufacturing Domain, Lovely Professional University, Phagwara, India)

Arjun Subramanian (Centre for Nanofibers and Nanotechnology Initiative, Department of Mechanical Engineering, National University of Singapore, Singapore)

Rahul Sahay (Division of Engineering Product Development, Singapore University of Technology and Design, Singapore)

Amutha Cinappan (Department of Mechanical Engineering, National University of Singapore, Singapore)

Seeram Ramakrishna (Department of Mechanical Engineering, National University of Singapore, Singapore)

Rapid Prototyping Journal

ISSN: 1355-2546

Article publication date: 24 June 2020

Issue publication date: 23 July 2020

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Abstract

Purpose

In the past decade, three-dimensional (3D) printing has gained attention in areas such as medicine, engineering, manufacturing art and most recently in education. In biomedical, the development of a wide range of biomaterials has catalysed the considerable role of 3D printing (3DP), where it functions as synthetic frameworks in the form of scaffolds, constructs or matrices. The purpose of this paper is to present the state-of-the-art literature coverage of 3DP applications in tissue engineering (such as customized scaffoldings and organs, and regenerative medicine).

Design/methodology/approach

This review focusses on various 3DP techniques and biomaterials for tissue engineering (TE) applications. The literature reviewed in the manuscript has been collected from various journal search engines including Google Scholar, Research Gate, Academia, PubMed, Scopus, EMBASE, Cochrane Library and Web of Science. The keywords that have been selected for the searches were 3 D printing, tissue engineering, scaffoldings, organs, regenerative medicine, biomaterials, standards, applications and future directions. Further, the sub-classifications of the keyword, wherever possible, have been used as sectioned/sub-sectioned in the manuscript.

Findings

3DP techniques have many applications in biomedical and TE (B-TE), as covered in the literature. Customized structures for B-TE applications are easy and cost-effective to manufacture through 3DP, whereas on many occasions, conventional technologies generally become incompatible. For this, this new class of manufacturing must be explored to further capabilities for many potential applications.

Originality/value

This review paper presents a comprehensive study of the various types of 3DP technologies in the light of their possible B-TE application as well as provides a future roadmap.

Keywords

  • 3D printing
  • Biomaterial
  • Biomedical engineering
  • Regenerative medicine
  • Organs
  • Tissue
  • Scaffoldings
  • Standards

Acknowledgements

One of the authors Dr N. Poomathi thanks the Department of Science and Technology (DST), New Delhi for the award of the Women Scientist Fellowship under women scientist scheme (WOS-A).

Citation

Poomathi, N., Singh, S., Prakash, C., Subramanian, A., Sahay, R., Cinappan, A. and Ramakrishna, S. (2020), "3D printing in tissue engineering: a state of the art review of technologies and biomaterials", Rapid Prototyping Journal, Vol. 26 No. 7, pp. 1313-1334. https://doi.org/10.1108/RPJ-08-2018-0217

Publisher

:

Emerald Publishing Limited

Copyright © 2020, Emerald Publishing Limited

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