Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

Fabrication of cells containing gel modules to assemble modular tissue-engineered constructs

This article has been updated

Abstract

This paper describes a protocol to encapsulate cells in sub-millimeter-sized cylindrical collagen modules and to assemble these modules into a tissue-engineered construct within a continuous loop flow circuit. Modules are fabricated by gelling a solution of collagen, that contains suspended cells, within the lumen of a small-bore polyethylene tube. The tubing is then cut into short lengths using an automated cutter and gently vortexed to remove the cell-containing collagen modules from the tubing lumen. Modules are then randomly assembled into a modular construct by pipetting a suspension of modules into a larger tube that is positioned within a continuous flow circuit. A range of cylinder aspect ratios are achievable; therefore, this method could potentially be used to create short discs or, alternatively, long threads of soft gels, with or without encapsulated cells, for a variety of tissue-engineering applications. Module fabrication requires 1 d and assembly of a modular construct requires 2 h.

NOTE: The title of the article is incorrect as published. It should read: "Fabrication of cell-containing gel modules to assemble modular tissue-engineered constructs".

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Modular construct design.
Figure 2: Schematic of the module fabrication process.
Figure 3: Light microscopy images of modules fabricated using a gel-cutting process.
Figure 4: Assembled modular construct.

Similar content being viewed by others

Change history

  • 08 March 2007

    The title of the article is incorrect as published. It should read: "Fabrication of cell-containing gel modules to assemble modular tissue-engineered constructs".

References

  1. Langer, R. & Vacanti, J.P. Tissue engineering. Science 260, 920 (1993).

    Article  CAS  Google Scholar 

  2. Nomi, M., Atala, A., Coppi, P.D. & Soker, S. Principals of neovascularization for tissue engineering. Mol. Aspects Med. 23, 463 (2002).

    Article  CAS  Google Scholar 

  3. Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407, 249 (2000).

    Article  CAS  Google Scholar 

  4. Kim, B.S., Putnam, A.J., Kulik, T.J. & Mooney, D.J. Optimizing seeding and culture methods to engineer smooth muscle tissue on biodegradable polymer matrices. Biotechnol. Bioeng. 57, 46–54 (1998).

    Article  CAS  Google Scholar 

  5. McGuigan, A.P. & Sefton, M.V. Vascularized organoid engineered by modular assembly enables blood perfusion. Proc. Natl. Acad. Sci. USA 103, 11461 (2006).

    Article  CAS  Google Scholar 

  6. Sosnik, A. & Sefton, M.V. Biomaterials 26, 7425–7435 (2005).

    Article  CAS  Google Scholar 

  7. Lahooti, S. & Sefton, M.V. Methods for Microencapsulation with HEMA-MMA. Methods in Molecular Medicine. Vol 18: Tissue Engineering Methods and Protocols (eds. Morgan, J.R. & Yamush, M.L.) 331–348 (Humana Press Inc., Totowa, New Jersey, USA, 1999).

    Google Scholar 

Download references

Acknowledgements

We would like to acknowledge Z. Fang, of FCS Technologies Inc., and T. Fixler for technical assistance; and the National Institute of Health (EB001013, co-investigators E. Yeo and A. Gotlieb) and the Natural Sciences and Engineering Research Council for funding. A.P.M. and B.L. acknowledge the fellowship support of the Province of Ontario and the Canadian Institutes of Health Research Training Program in Regenerative Medicine.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alison P McGuigan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

Automatic cutter concept drawing (PDF 74 kb)

Supplementary Figure 2

[a–d] Module fabrication process (PDF 1089 kb)

Supplementary Figure 3

Preliminary Assembly of the Flow Circuit for gas sterilization (PDF 71 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

McGuigan, A., Leung, B. & Sefton, M. Fabrication of cells containing gel modules to assemble modular tissue-engineered constructs. Nat Protoc 1, 2963–2969 (2006). https://doi.org/10.1038/nprot.2006.443

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2006.443

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing